Serum Carcinoembryonic Antigen Research Articles

Association of preoperative and recurrent serum carcinoembryonic antigen and outcome of colorectal cancer patients with metastatic relapse

BackgroundSeldom have the associations of preoperative CEA (p-CEA) and recurrent CEA (r-CEA) levels as well as changes in p-CEA and r-CEA with survival in patients with stage I–III colorectal cancer (CRC) who have experienced metastatic relapse, been thoroughly examined. Methods241 consecutive patients with stage I–III CRC who experienced metastatic relapse at Fudan University Shanghai Cancer Center (FUSCC) between January 2008 and January 2016 were investigated. The influence of p-CEA, r-CEA and CEA alteration on the overall survival (OS) and relapse-to-death survival (RDS) was evaluated. The restricted cubic spline regression model was employed to explore the optimal cut-off value of CEA. ResultsAll 241 patients were categorized into four groups built on their CEA alteration patterns as follows: A, patients presenting elevated p-CEA levels but normal r-CEA levels (P–N); B, patients displaying normal levels of both p-CEA and r-CEA (N–N); C, patients exhibiting elevated levels of both p-CEA and r-CEA (P–P); D, patients with normal p-CEA levels but elevated r-CEA levels (N–P). The correlation between p-CEA and OS (P = 0.3266) and RDS (P = 0.2263) was insignificant. However, r-CEA exhibited a significant association with both OS (P = 0.0005) and RDS (P = 0.0002). Group A demonstrated the longest OS and RDS, whereas group D exhibited the poorest OS and RDS outcomes. For both OS and RDS, the CEA alteration groups served as an independent prognostic indicator. The optimal cut-off threshold for CEA was determined to be 5.1 ng/ml via the restricted cubic spline regression model. Conclusionr-CEA has a stronger correlation with OS and RDS in individuals with stage I–III CRC who have experienced metastatic relapse.The change between p-CEA and r-CEA could further indicate post-relapse survival, thereby facilitating the assessment of mortality risk stratification in stage I-III CRC patients experiencing metastatic relapse.

Clinical value of KiSS-1 and MMP-2 expression levels in breast cancer tissue in evaluating prognosis of elderly breast cancer patients after modified radical mastectomy.

We attempted to clarify clinical value of KiSS-1 and MMP-2 levels in breast cancer (BC) tissue in evaluating prognosis of elderly BC patients after modified radical mastectomy (MCM). The data of 192 elderly female BC patients receiving MCM in our hospital from January 2018 to December 2022 were collected. According to prognosis, patients received division into poor prognosis group (n = 43) and good prognosis group (n = 149). The serum CEA level and KiSS-1 and MMP-2 levels in BC tissue received measurement in both groups. The predictive value of KiSS-1 and MMP-2 alone and jointly in adverse prognosis of elderly BC patients after MCM received assessment. Results showed that No statistical significance was exhibited between both groups in general data (P > 0.05). The serum CEA level and MMP-2 expression in BC tissue in poor prognosis group exhibited elevation relative to those in good prognosis group, and KiSS-1 expression in BC tissue in poor prognosis group exhibited depletion relative to that in good prognosis group, indicating statistical significance (P < 0.05). The high-level KiSS-1 might be a protective element for adverse prognosis of elderly BC patients after MCM, and high-level CEA and MMP-2 might be an independent risk element for adverse prognosis of elderly BC patients after MCM (P < 0.05). KiSS-1 and MMP-2 alone and jointly predicted AUC of adverse prognosis in elderly BC patients after MCM were 0.93, 0.802 and 0.958, with certain predictive values; when cutoff values of KiSS-1 and MMP-2 were 6.15 and 2.26, the predictive value was the best. In conclusion, KiSS-1 and MMP-2 levels in BC tissue possess relation to adverse prognosis of MCM. KiSS-1 and MMP-2 levels in elderly BC patients before surgery may be detected in the future to assist in prognosis evaluation of elderly BC patients after MCM.

Combined detection of serum IL-6 and CEA contributes to the diagnosis of lung adenocarcinoma in situ.

Effective discrimination of lung adenocarcinoma (LUAD) in situ (AIS) from benign pulmonary nodules (BPN) is critical for the early diagnosis of AIS. Our pilot study in a small cohort of 90 serum samples has shown that serum interleukin 6 (IL-6) detection can distinguish AIS from BPN and health controls (HC). In this study, we intend to comprehensively define the diagnostic value of individual and combined detection of serum IL-6 related to the traditional tumor markers carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1) for AIS. The diagnostic performance of serum IL-6 along with CEA and CYFRA21-1 were evaluated in a large cohort of 300 serum samples by a chemiluminescence immunoassay and an electrochemiluminescence immunoassay. A training set comprised of 65 AIS, 65 BPN, and 65 HC samples was used to develop the predictive model for AIS. Data obtained from an independent validation set was applied to evaluate and validate the predictive model. In the training set, the levels of serum IL-6 and CEA in the AIS group were significantly higher than those in the BPN/HC group (P < 0.05). There was no significant difference in serum CYFRA21-1 levels between the AIS group and the BPN/HC group (P> 0.05). Serum IL-6 and CEA levels for AIS patients showed an area under the curve (AUC) of 0.622 with 23.1% sensitivity at 90.7% specificity, and an AUC of 0.672 with 24.6% sensitivity at 97.6% specificity, respectively. The combination of serum IL-6 and CEA presented an AUC of 0.739, with 60.0% sensitivity at 95.4% specificity. The combination of serum IL-6 and CEA showed an AUC of 0.767 for AIS patients, with 57.1% sensitivity at 91.4% specificity in the validation set. IL-6 shows potential as a prospective serum biomarker for the diagnosis of AIS, and the combination of serum IL-6 with CEA may contribute to increased accuracy in AIS diagnosis. However, it is worth noting that further research is still necessary to validate and optimize the diagnostic efficacy of these biomarkers and to address potential sensitivity limitations.

Abstract 1038: Identification of diagnostic biomarkers for colon adenocarcinoma by analyzing proteins in human-derived extracellular vesicles and particles

Abstract There is an unmet medical need for circulating biomarkers to improve early cancer detection in colon adenocarcinoma (COAD). We investigated the proteomic profile of extracellular vesicles and particles (EVPs) from the colon tissue explants and plasmas in COAD. The research aims to overcome the limitations of traditional serum Carcinoembryonic Antigen (CEA) testing and invasive procedures like colonoscopy. We analyzed EVPs sourced from tumor and adjacent non-tumor tissues and preoperative and postoperative plasma in COAD patients to identify potential EVP-based tumor diagnostic markers. In the Discovery phase with 50 COAD patients, we conducted a proteomic analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS), identifying approximately 50 markers each from tissue explants and plasma. These markers were validated in an independent cohort of 104 participants, including 84 COAD patients and 20 healthy controls. We utilized ELISA to quantify 11 selected EVP proteins. Notably, seven of these proteins exhibited significant differential expression in preoperative and postoperative plasma, highlighting their diagnostic relevance. These seven proteins also showed marked elevation in preoperative plasma compared to healthy controls, reinforcing their potential as diagnostic markers. The study extended to evaluate the diagnostic accuracy of these seven proteins, referred to as "EV-7 levels", across various stages of COAD. Their performance was compared with serum CEA levels and plasma cfDNA mutation rates, as detected by an FDA-approved liquid biopsy assay. The EV-7 levels demonstrated superior detection rates in the early stages of COAD, particularly in Stages I and II, in contrast to the serum CEA method. Among the 84 patients, 73 (86.9%) exhibited EV-7 levels exceeding the established cut-off. In the validation cohort, EV-7 levels were more accurate across different COAD stages than serum CEA levels and cfDNA mutation rates. CEA levels above 5 ng/ml were 27%, 45%, 42%, and 64% for Stages I through IV. cfDNA somatic mutation rates were 60%, 80%, 75%, and 75%. EV-7 levels exceeding the cut-off were 73%, 100%, 88%, and 84%, respectively, with Stages I and II having the highest detection rate among the three methods. ROC curve analysis for EV-7 levels in Stages I to IV showed statistically significant, with AUC values of 0.913, 1.000, 0.985, and 0.984, respectively. Our findings indicate that the seven EVP proteins are significantly present in the plasma of early-stage COAD patients. Integrating these markers with current diagnostic approaches could improve early cancer detection, showing promise for practical application in clinical settings. Citation Format: Yura Seo, Yoon Dae Han, Linda Bojmar, Kyung-A Kim, Yurin Seo, David Lyden, Han Sang Kim. Identification of diagnostic biomarkers for colon adenocarcinoma by analyzing proteins in human-derived extracellular vesicles and particles [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1038.

Abstract 7289: PancreaAlert: Intelligent nanoengineered biosensor for pancreatic cancer

Abstract Introduction: Pancreatic cancer accounts for 3% of cancer cases and 7% of cancer deaths in the United States. It is currently in the third position with respect to cancer-related deaths, and it is expected to move to second place as of 2040. This is mainly due to its diagnosis in the later stage. If detected in the first or second stage surgery can be performed thus increasing the patient’s survival rate. The current methods of diagnosis cannot do early stage or asymptomatic detection. So, detecting cancer-specific biomarkers can aid in the prognosis. Serum protein-based biomarkers carbohydrate antigen CA242, CA19-9, and carcinoembryonic antigen CEA are specific to pancreatic cancer. Thus, in this preliminary study, we aim to develop a nanoengineered electrochemical biosensor combined with machine learning to detect pancreatic cancer-specific biomarkers CA242, CA19-9, and CEA. Methodology: Nanoengineering the biosensor: The gold working electrode of the gold- biosensor (DRP-250AT) was coated with graphene oxide nano colloidal solution and kept in UV overnight for the graphene oxide nanosheet to crosslink with the working electrode. Detection of biomarkers using an electrochemical biosensor: First, a Crosslinker (DSP) was added to ethanol cleaned biosensor to bind the analytes. Following that antibody specific to each biomarker were added to the biosensors. The addition of TBS superblock prevented non-specific binding. Then different concentrations of biomarkers were added, and the corresponding sensor was subjected to various electrochemical analyses such as electrochemical impedance spectroscopy and voltammetry. SEM-EDAX analysis: The antigen-antibody binding on the biosensor's surface was confirmed. Automation and machine learning: Python code was developed to automate the analysis process and machine learning models (support vector machine and neural network) were used to classify the concentrations into various risk levels. The sensitivity of the developed tool was high when compared with conventional methods like ELISA and confocal microscopy. Results: From the electrochemical studies we found that with increasing concentration of biomarkers, there was a trend in output parameters: capacitance, resistance, impedance and area under the curve. By analyzing this trend, the concentrations of biomarkers can be detected. Using this data as input the machine learning model (accuracy greater than 80%) classified the concentrations into risk levels (normal, low risk, and high risk). Significance: Nanoengineering with graphene oxide nanosheets enhances the sensitivity of electrochemical biosensors. Automation and machine learning models help in the analysis of large datasets produced by this sensor. Overall, this device aids in the prognosis of pancreatic cancer. Our preliminary results are encouraging but more thorough research is required to make this diagnostic tool a working application. Citation Format: Meenal Karunanidhi, Hemalatha Kanniyappan, Edith Zhan, Ruth Mathew, Yani Sun, Junyi Wu, Yan Yan, Gnanasekar Munirathinum, Mathew T. Mathew. PancreaAlert: Intelligent nanoengineered biosensor for pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7289.

Abstract 3673: Monitoring treatment response in patients with metastatic colorectal cancer using cfDNA fragmentomics testing: The DOLPHIN trial

Abstract Background: Accurate monitoring of treatment response in patients with metastatic colorectal cancer (mCRC) is important to decide when to adjust treatment regimen or to proceed to local therapy of metastases. At present, clinical response is determined by computed tomography (CT) imaging-based assessment of changes in tumor size. However, this monitoring approach is constrained by limited sensitivity in detecting lymph node and peritoneal metastases, as well as inter-reader variability. Detection of circulating tumor DNA (ctDNA) is indicative of the amount of neoplastic cells and may have added clinical value to CT imaging for assessment of treatment response and guidance in treatment decision making in mCRC patients. We recently developed a tumor mutation-independent ctDNA test that utilizes low-coverage whole genome sequencing to analyze the plasma cell-free DNA (cfDNA) fragmentome to measure the ctDNA tumor fraction: the DELFI-tumor fraction (DELFI-TF) score. Aim: The DOLPHIN study aims to investigate whether the DELFI-TF ctDNA assay can provide a sensitive, affordable and broadly applicable ctDNA test to monitor treatment response of mCRC patients. Methods: The prospective, observational, multi-center DOLPHIN study is a substudy of the Prospective Dutch ColoRectal Cancer cohort (PLCRC). Clinical data, images and blood samples from 400 patients receiving systemic therapy in 8-10 Dutch hospitals will be collected. Blood samples will be drawn longitudinally in conjunction with regularly scheduled CT imaging. Plasma cfDNA will be analyzed for tumor-specific fragmentation patterns using the DELFI-TF score. Droplet digital PCR ctDNA-testing of RAS/RAF hotspot mutations will be performed as reference, when feasible. Primary endpoint is the association between ctDNA changes and clinical response. Secondary endpoints are the association between ctDNA changes and radiological response according to RECIST and to serum carcinoembryonic antigen (CEA) at various time points during systemic treatment, lead time of ctDNA-testing compared to CT imaging to detect progressive disease, and the prognostic value of longitudinal ctDNA-testing. Results: Since the inclusion of the first patient in March 2023, 117 patients have been included in the DOLPHIN study (November 2023). Seven hospitals throughout the Netherlands are currently open for patient inclusion and more sites have been approached to participate. Discussion: The DOLPHIN study will assess the added clinical value of longitudinal ctDNA-testing in treatment response monitoring of mCRC patients and whether imaging can be complemented and/or partly replaced by ctDNA-testing. The results of this study may lead to novel strategies for monitoring treatment response and to ctDNA-guided treatment decision making in mCRC patients. Citation Format: Denise E. van Steijn, Remond J. Fijneman, Geraldine R. Vink, Jeanine M. Roodhart, Miriam Koopman, Max J. Lahaye, Manon N.G. Braat, Veerle M. Coupé, Daan A. van den Broek, Gerrit A. Meijer, Haoyue Wang, Marjolein J. Greuter, Birgit I. Lissenberg-Witte, Lorenzo Rinaldi, E Peters, Alissa Konicki, Nicholas C. Dracopoli, Niels F. Kok, Victor E. Velculescu. Monitoring treatment response in patients with metastatic colorectal cancer using cfDNA fragmentomics testing: The DOLPHIN trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3673.

Abstract 6408: Early carcinoembryonic antigen (CEA) dynamics to predict the efficacy of fruquintinib (F) + best supportive care (BSC) in patients with metastatic colorectal cancer (mCRC) enrolled in FRESCO-2

Abstract Background: The phase 3 FRESCO-2 trial (NCT04322539) demonstrated a significant survival benefit with fruquintinib (F) + BSC vs placebo (P) + BSC as third or later line of therapy for patients (pts) with mCRC. Based on the results of FRESCO-2, F was FDA-approved for adults with previously treated mCRC, irrespective of biomarker status. In mCRC, CEA levels and imaging are routinely used to monitor response to systemic therapy. We investigated early CEA changes during treatment in FRESCO-2 and possible relationships with efficacy. Methods: Pts with abnormal baseline (BL) CEA were included based on local lab reference ranges. Serum CEA levels were measured at BL and Day 1 (D1) of each 28-day cycle (C) except C1. Changes in CEA levels were analyzed at C2D1 and C3D1. CEA response was defined as ≥50% decrease from BL, and CEA progression was defined as ≥100% increase from BL. Tumor evaluation was performed by CT or MRI scan every 2 cycles. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method; hazard ratio (HR) was estimated via Cox proportional hazards model; p-value was generated from log rank test. Results: Overall, 88.3% (407/461) vs 90.4% (208/230) of pts had abnormal BL CEA in F vs P arms; median BL CEA values were similar between treatment arms (Table). At C3D1, the proportion of pts who had a CEA response was significantly higher with F vs P (35.5% vs 3.8%, P &amp;lt;0.001) and the proportion who had CEA progression was significantly lower (5.7% vs 47.2%, P &amp;lt;0.001). Pts in the F arm with CEA response at C3D1 had improved OS and PFS vs pts without CEA response and pts with CEA progression (Table). These results were consistent for pts who had an early CEA response at C2D1 (Table). Conclusion: CEA response at C2D1 and C3D1 could be considered an early predictor for improved OS and PFS. Pts with CEA response seem to benefit from F + BSC compared with pts without response or with CEA progression. Table. CEA changes from baseline in pts in the F + BSC vs P + BSC arms, and OS and PFS based on CEA response in pts in the F + BSC arm CEA changes from baseline by treatment arm (ITT population) F + BSC (N=461) P + BSC (N=230) Baseline, n 407 208 Median CEA (range), µg/L 132.4 (3.0-213000.0) 169.6 (3.2-90010.0) C2D1, n 340 151 Median CEA (range), µg/L 93.3 (2.0-98660.0) 133.5 (2.7-255910.0) Median change from baseline (range), % -19.2 (-90.5-467.8) 44.2 (-61.7-606.8) C3D1, n 245 53 Median CEA (range), µg/L 78.3 (1.7-133390.0) 145.2 (3.9-17782.0) Median change from baseline (range), % -31.0 (-91.4-2195.8) 90.5 (-68.9-3776.6) OS and PFS for pts in the F + BSC arm with or without CEA response at C2D1 and C3D1 Pts with early CEA response at C2D1(n=66) Pts without early CEA response at C2D1 (n=274) Pts with CEA response at C3D1 (n=87) Pts without CEA response at C3D1 (n=158) Median OS, months 10.0 7.4 11.1 8.5 HR (95% CI), P value 0.62 (0.44-0.89), P = 0.009 0.65 (0.46-0.92), P = 0.015 Median PFS, months 5.6 3.7 5.8 4.2 HR (95% CI), P value 0.68 (0.51-0.92), P = 0.01 0.58 (0.44-0.78), P = 0.0003 OS and PFS for pts in the F + BSC arm with CEA response or CEA progression at C2D1 and C3D1 Pts with early CEA response at C2D1(n=66) Pts with early CEA progression at C2D1 (n=15) Pts with CEA response at C3D1 (n=87) Pts with CEA progression at C3D1 (n=14) Median OS, months 10.0 4.3 11.1 5.6 HR (95% CI), P value 0.27 (0.14-0.51), P &amp;lt;0.0001 0.23 (0.12-0.45), P &amp;lt;0.0001 Median PFS, months 5.6 1.9 5.8 3.4 HR (95% CI), P value 0.30 (0.16-0.56), P &amp;lt;0.0001 0.25 (0.13-0.48), P &amp;lt;0.0001 Citation Format: Sara Lonardi, Arvind Dasari, Rocio Garcia-Carbonero, Takayuki Yoshino, Pilar García-Alfonso, Judit Kocsis, Chiara Cremolini, François Ghiringhelli, Ardaman Shergill, Howard S Hochster, Michel Ducreux, Dirk Arnold, Varsha Sundaresan, Siddha Kasar, Adela Pina, Ziji Yu, William R Schelman, Lucy Chen, Josep Tabernero. Early carcinoembryonic antigen (CEA) dynamics to predict the efficacy of fruquintinib (F) + best supportive care (BSC) in patients with metastatic colorectal cancer (mCRC) enrolled in FRESCO-2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6408.

Clinical value of combined detection of Carcinoembryonic Antigen and CA125 in the diagnosis of non-small cell lung cancer combined with Malignant Pleural Effusion.

To investigate the clinical value of combined detection of carcinoembryonic antigen(CEA) and CA125 in the diagnosis of non-small cell lung cancer(NSCLC) combined with malignant pleural effusion. This was retrospective research. Fifty-six NSCLC patients combined with malignant pleural effusion in Baoding No.1 Hospital, China, from January 2020 to January 2022 were recruited as the malignant group, and another 56 NSCLC patients combined with pleural effusion in the same period were recruited as the benign group. Pleural effusion and serum specimens were collected from both groups and their carcinoembryonic antigen (CEA), carbohydrate antigen 125(CA125) and SP70 antigen levels were measured respectively. The differences in index levels between the two groups were compared, and the value of the index in diagnosing NSCLC combined with malignant pleural effusion was analyzed. The positive rates of CEA, CA125 and SP70 antigen in pleural effusion were higher in the malignant group than in the benign group (p>0.05); The positive rates of CEA and CA125 in the malignant group were higher than those in the benign group (p>0.05), with no statistically significant difference between the two groups in the positive rates of SP70 antigen (p>0.05). ROC curve analysis revealed the value of serum CEA and CA12 in the diagnosis of NSCLC combined with malignant pleural effusion, while serum SP70 antigen had no diagnostic value (p>0.05). The combined detection of CEA, CA125 and SP70 antigen boasts a higher diagnostic value for NSCLC-mediated pleural effusion, with higher diagnostic value than the combined detection of serum indexes.

3D gold dendrite and reduced graphene oxide-chitosan nanocomposite-based immunosensor for carcinoembryonic antigen detection in clinical settings

Electrodeposited metallic nanostructures with tree-like hierarchical morphology, often termed metallic nanodendrites (MNDs), are gradually gaining interest in the development of electrochemical biosensors. Noble metal nanodendrites exhibit exceptional conductive and electrocatalytic activity. In this work, we have reported a robust method of electrodeposition of gold nanodendrites (AuND). In order to achieve this, we first optimized the number of gold nanoparticles (AuNP) as seed molecules on the sensor surface and observed that “less seed” resulted in enhanced growth of AuND. Thereafter, AuNP/AuND was used as an excellent surface in conjugation with reduced graphene oxide (rGO), chitosan (CS), and an Anti-CEA antibody for electrochemical detection of carcinoembryonic antigen (CEA), a clinically established cancer biomarker. The developed immunosensor, glassy carbon electrode/gold nanoparticle/gold nanodendrites/chitosan-reduced graphene oxide/Anti-CEA antibody (GCE/AuNP/AuND/CS-rGO/Anti-CEA), is capable of detecting the biomarker in the linear dynamic range (LDR) of 1 × 10−13 to 1 × 10−8 g/mL, which covers the normal as well as clinical range of CEA in serum with a limit of detection (LOD) of 2.23 (±0.03) x 10−14 g/mL. Real sample analysis was performed in serum with a recovery rate ranging between 90 and 99.20 %, demonstrating the feasibility of the sensors for CEA monitoring.

Epitope imprinted electrochemical sensor for highly sensitive detection of alpha-fetoprotein

A selective and sensitive epitope imprinted electrochemical sensor for the precise quantification of alpha-fetoprotein (AFP) was developed through electropolymerization by using the C-terminus of alpha-fetoprotein as the template and o-phenylenediamine as the functional monomer. The prepared epitope molecularly imprinted polymer film was characterized by the scanning electron microscope (SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Experimental parameters including the molar ratio of template to functional monomer, electropolymerization cycle, elution time and rebinding time were systemically investigated and optimized. Under optimized conditions, the proposed epitope imprinted electrochemical sensor demonstrated outstanding sensing capabilities within the alpha-fetoprotein concentration range of 0.1 pg mL−1 to 1.0 μg mL−1, with a limit of detection of 0.075 pg mL−1. Furthermore, this electrochemical sensor exhibited exceptional selectivity when tested against other proteins or disease biomarkers, including human serum albumin, bovine serum albumin, prostate-specific antigen and carcinoembryonic antigen. In practical application, it was successfully employed for the analysis of alpha-fetoprotein in human serum samples, yielding a recovery rate ranging from 99.70 % to 108.48 %. This study proposed a straightforward approach for the construction of epitope molecularly imprinted electrochemical sensor tailored for the determination of alpha-fetoprotein.

Prediction of pathologic complete response to neoadjuvant chemoradiation in locally advanced rectal cancer.

To investigate the predictive factors of pathologic complete response (pCR) in locally advanced rectal cancer (LARC) patients who had been treated with neoadjuvant chemoradiation (nCRT). For this retrospective study, 53 LARC patients (37 males and 16 females; age range 25 to 79 years) were selected. Clinical characteristics, baseline mrTNM staging, MR gross tumor volumes (GTV), and pCR were evaluated. The diagnostic accuracy of GTV for predicting pCR was calculated. Among 53 LARC patients, 15 patients achieved pCR (28.3%), while 38 patients achieved non-pCR. Only three (5.7%) out of 53 patients did not downstage after nCRT. GTV and tumor differentiation were the significant prognostic parameters for predicting pCR. A tumor volume threshold of 21.1 cm3 was determined as a predictor for pCR, with a sensitivity of 84% and specificity of 47%. In addition, GTV was associated with mrN stage, circumferential resection margin (CRM) status, extramural vascular invasion (EMVI) status, and pretreatment serum CEA level. Tumor volume and tumor differentiation have significant predictive values in preoperative assessment of pCR among LARC patients. These findings aid clinicians to discriminate those patients who may likely benefit from preoperative regimens and to make optimal treatment plans.

Impact of Micronutrient Profiles on the Pathological Features and Clinical Outcomes of Colorectal Tumors with Microsatellite Instability

We assessed the role of nutritional factors in conjunction with pathological and clinical characteristics of colorectal tumors with microsatellite instability. Data from 1,135 patients diagnosed with colorectal cancer were analyzed, employing immunohistochemistry for mismatch repair protein detection and polymerase chain reaction-capillary electrophoresis for microsatellite instability gene detection. To explore potential correlations with microsatellite instability status, we evaluated patients’ dietary habits and micronutrient levels, particularly folate and selenium. We discovered that 10.84% of the patients had mismatch repair protein deletions, with MLH1 and PMS2 double deletions being the most prevalent. Notable differences were identified in serum carcinoembryonic antigen levels, tumor location, tumor-node-metastasis stage, tumor differentiation, mucous composition, gross type, size, nodules, nerve invasion, and lymph node ratio between deficient mismatch repair and proficient mismatch repair patients. The deficient mismatch repair group had lower carcinoembryonic antigen levels, a higher incidence of right-sided colon cancer, earlier tumor-node-metastasis stage, poorer differentiation, more mucinous components, larger tumors, and fewer nodules and nerve invasions. High concordance (98.59%) was observed between immunohistochemistry and polymerase chain reaction-capillary electrophoresis techniques in microsatellite instability detection, underscoring the reliability of these methods. Integrating the nutritional parameters with conventional clinical assessments offers a nuanced understanding of the heterogeneity of colorectal cancer, with significant implications for diagnosis and treatment strategies.

Bio-functionalized carbon dots for signaling immuno-reaction of carcinoembryonic antigen in an electrochemical biosensor for cancer biomarker detection

Early diagnosis of cancer demands sensitive and accurate detection of cancer biomarkers in blood. Carbon dots (CDs) bio-functionalization with antibodies, peptides or aptamers have played significant role in cancer diagnosis and targeted cancer therapy. Herein, a biosensor for detection of cancer biomarker carcinoembryonic antigen (CEA) in blood serum has been designed using CDs bio-functionalized with HRP-conjugated CEA antibody (CUCDs@CEAAb2) as detection probe. CDs were synthesized by upscaling of cow urine, a nitrogen rich biomass waste, by hydrothermal method. Detection probe based on CDs resulted in 3.5 times higher sensitivity as compared to conventional electrochemical sandwich immunoassay. To further improve the sensor performance, hyper-branched polyethylenimine grafted poly amino aniline (PEI-g-PAANI) was used as the sensing interface, which enabled immobilization of higher amount of capture antibody. Detection of CEA in human blood serum coupled with wide linear range (0.5–50 ng/ml), good specificity, stability, reproducibility and low detection limit (10 pg/ml) signified the excellence of CUCDs based CEA immunosensor. CUCDs exhibited excitation wavelength dependent fluorescence property and showed strong blue emission under UV irradiation. MTT assay indicated that the material is not toxic towards human dental pulp stem cells (hDPSCs) and MG63 osteosarcoma cells (cell viability > 90%). The present study demonstrates a methodology for valorization of animal waste to a cost-effective carbon based functional nanomaterial for clinical detection of cancer biomarkers.

Observations of the effectiveness, dosage, and prognosis of intensity-modulated radiation therapy under ultrasonic guidance for cervical cancer patients.

Volumetric modulated arc therapy (VMAT) guided by ultrasound is a novel radiation therapy technique that facilitates the delineation of the tumor target area under image guidance, enhancing the precision of radiation therapy and maximizing the protection of surrounding tissues. The objective of this paper is to investigate the effectiveness of VMAT under ultrasonic guidance for cervical cancer patients and its impact on radiotherapy dosage and prognosis. A retrospective analysis encompassed 128 instances of cervical cancer patients who were admitted to our medical facility between April 2019 and April 2021. The patients were categorized into an observation cohort and a control cohort, depending on variations in treatment modalities post-admission. The control group underwent conventional radiotherapy, whereas the observation group received VMAT guided by ultrasound. Clinical efficacy, average radiation dosages (in the radiotherapy target area, rectum, and bladder), radiotherapy-related toxicities during treatment, and one-year survival rates were compared between the two groups. Additionally, variances in pre- and post-treatment serum levels of squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen (CEA), and carbohydrate antigen 724 (CA724) were subjected to assessment. When compared to the control group (64.52%), the observation cohort's comprehensive effectiveness rate was considerably greater (80.30%). The observation group saw lower average radiation exposures and a reduction in the post-treatment concentrations of CEA, SCC-Ag, and CA724. The overall incidence of adverse effects from radiation treatment also declined. The observation group had a greater one-year survival rate (90.48%) than the control group (73.33%). When comparing the observation cohort to the control group, Kaplan-Meier survival analysis showed a significantly higher one-year survival rate (Log-Rank = 6.530, P= 0.011). VMAT guided by ultrasound for patients with cervical cancer demonstrates promising short- and long-term treatment outcomes. It also leads to improvements in serum CEA, SCC-Ag, and CA724 levels, as well as reductions in the average radiation dosages to the radiotherapy target area, rectum, and bladder. This approach warrants attention from clinicians in clinical practice.

Immune function status of postoperative patients with colon cancer for predicting liver metastasis.

Colon cancer (CC) has a high incidence rate. Radical resection is the main treatment method for CC; however, liver metastasis (LM) often occurs post-surgery. The liver contains both innate and adaptive immune cells that monitor and remove abnormal cells and pathogens. Before LM, tumor cells secrete cytokines and exosomes to adjust the immune microenvironment of the liver, thus forming an inhibitory immune microenvironment for colonization by circulating tumor cells. This indicates that the immune state of patients with CC plays a crucial role in the occurrence and progression of LM. To observe and analyze the relationship between immune status and expression of tumor factors in patients with LM of CC, and to provide a scientific intervention method for promoting the patient prognosis. A retrospective analysis was performed. The baseline data of 100 patients with CC and 100 patients with CC who suffered from postoperative LM and were admitted to our hospital from May 2021 to May 2023 were included in the non-occurrence and occurrence groups, respectively. The immune status of the patients and the expression of tumor factor-related indicators in the two groups were compared, and the predictive value of the indicators for postoperative LM in patients with CC was analyzed. Compared with the non-occurrence group, the expression of serum carcinoembryonic antigen (CEA), CA19-9, CA242, CA72-4 and CA50 in patients in the occurrence group were significantly higher, while the expression of CD3+, CD4+, CD8+, natural killer (NK) and CD4+/CD25 in patients in the occurrence group were significantly lower (P < 0.05). No significant difference was observed in other baseline data between groups (P > 0.05). Multivariate logistic regression model analysis revealed that the expressions of CEA, CA19-9, CA242, CA72-4, CA50, CD3+, CD4+, CD8+, NK, and CD4+/CD25 were associated with the LM in patients with CC. High expressions of serum CEA, CA19-9, CA242, CA72-4 and CA50, and low expressions of CD3+, CD4+, CD8+, NK, and CD4+/CD25 in patients with CC were risk factors for LM (OR > 1, P < 0.05). The receiver operating characteristic curve showed that the area under curve for CEA, CA19-9, CA242, CA72-4, CA50, CD3+, CD4+, CD8+, NK, and CD4+/CD25 in the prediction of LM in patients with CC were all > 0.80, with a high predictive value. The expression of tumor factors and immune state-related indices in patients with CC is closely associated with the occurrence of LM.

CT-guided radioactive 125I seeds brachytherapy for lung oligometastases from colorectal cancer: initial results.

To evaluate the safety and effectiveness of computed tomography (CT)-guided radioactive 125I seeds brachytherapy (RISB) for lung oligometastases (LO) from colorectal cancer (CRC). Data for 144 LOs from 70 CRC patients who underwent CT-guided RISB were retrospectively analyzed. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoints were technical success, local control rate (LCR), and complications. Kaplan-Meier method was used for survival analysis. Cox model was used to identify the independent predictors of poor prognosis. The RISB procedures were successfully performed in all patients, and the success rate was 100%. The median follow-up was 27.8months. The median PFS was 10.0months (95% CI: 8.9-11.1) and the 1- and 2-year PFS rates were 32.9% and 5.9%, respectively. On multivariate analysis, serum carcinoembryonic antigen (CEA) ≤ 15ng/ml (P = 0.048), middle-high differentiated pathological classification (P = 0.015), primary TNM stages I-III (P = 0.001), LO number ≤ 2 (P < 0.001) and cumulative gross tumor volume (GTV) ≤ 40 cm3 (P < 0.001) showed superior PFS. The median OS was 30.8months (95% CI: 27.1-34.4) and the 1-, 2-, and 3-year OS rates were 95.7%, 67.4%, and 42.5%, respectively. On multivariate analysis, serum CEA ≤ 15ng/ml (P = 0.004), middle-high differentiated pathological classification (P < 0.001), primary TNM stages I-III (P < 0.001), LO number ≤ 2 (P < 0.001), cumulative GTV ≤ 40 cm3 (P < 0.001) and system treatments combined with chemotherapy and target therapy (P < 0.001) showed superior OS. The LCR for 3, 6, and 12months was 97.9%, 91.0%, and 83.6%, respectively. There were 4 cases of pneumothorax at 5.7% that required drainage. RISB for LO from CRC is safe and effective, and serum CEA, TNM stage, LO number, cumulative GTV, and system treatments should be emphasized for long OS.

Ultrasonographic features of thyroid carcinoma of different sizes: comparison between medullary thyroid carcinomas and papillary thyroid carcinomas

Objective: To investigate the ultrasonographic features of medullary thyroid carcinomas (MTCs) of different sizes and supply valid information for separating MTCs from papillary thyroid carcinomas (PTCs). Methods: There were 87 patients with MTC and 220 patients with PTC detected by ultrasonography and confirmed by pathology at Tianjin Medical University Cancer Institute and Hospital from June 2018 to March 2022. Nodules were divided into the large nodule group (the maximum diameter of the tumor was＞1 cm) and the small nodule group (the maximum diameter of the tumor was ≤1 cm). There were 97 cases in the small nodule group, including 28 cases of MTC and 69 cases of PTC. There were 210 cases in the large nodule group, including 59 cases of MTC and 151 cases of PTC. After stratification by thyroid nodules, ultrasonographic features of thyroid nodules and metastatic lymph nodes, preoperative serum calcitonin (CT) and carcinoembryonic antigen (CEA) levels were compared between MTC and PTC patients. Results: In the small nodule group, the proportion of MTCs exhibiting hypoecho, smooth margins, and having blood flow signals was higher than that of PTCs, with statistically significant differences (all P＜0.05). In the large nodule group, the proportion of MTCs showing cystic solidity, hypoecho, smooth margins, blood flow, and the type Ⅳvascular distribution was higher than PTCs, and the difference of calcification type between them was also statistically significant (all P＜0.05). In contrast, the differences in the number of lesions and aspect ratio between MTCs and PTCs were not statistically significant regardless of nodule size (all P＞0.05). In the small nodule group,6 metastatic lymph nodes of medullary thyroid carcinoma (LNM-MTC) and 11 metastatic lymph nodes of papillary thyroid carcinoma (LNM-PTC) were correctly diagnosed by ultrasound, respectively. The diagnostic compliance rate of ultrasound was 78.6% (22/28) and 78.3% (54/69), respectively, with no statistically significant difference (P=0.973). In the large nodule group, 28 LNM-MTC and 11 LNM-PTC were correctly diagnosed by ultrasound, respectively. The diagnostic compliance of ultrasound was 88.1% (52/59) and 73.5% (111/151), respectively, which was statistically significant (P=0.022). Among them, 82.1% of LNM-MTC and 56.6% of LNM-PTC showed abnormal blood flow signals, with a statistically significant difference (P=0.016). There were significant differences in preoperative serum CT and CEA levels of different sizes of MTCs (all P＜0.05). Conclusions: Different sizes of MTCs require diverse demonstrative criteria. Abnormal blood flow signal is of great significance in the diagnosis of LNM-MTC. Within the absence of ultrasonic characteristics, preoperative serum CT test can provide confidence for the diagnosis of MTC.

CircUSP1 as a novel marker promotes gastric cancer progression via stabilizing HuR to upregulate USP1 and Vimentin

Circular RNAs (circRNAs) play a crucial role in regulating various tumors. However, their biological functions and mechanisms in gastric cancer (GC) have not been well understood. Here, we discovered a stable cytoplasmic circRNA named circUSP1 (hsa_circ_000613) in GC. CircUSP1 upregulation in GC tissues was correlated with tumor size and differentiation. We observed that circUSP1 promoted GC growth and metastasis. Mechanistically, circUSP1 mainly interacted with the RRM1 domain of an RNA-binding protein (RBP) called HuR, stabilizing its protein level by inhibiting β-TrCP-mediated ubiquitination degradation. The oncogenic properties of HuR mediated promotive effects of circUSP1 in GC progression. Moreover, we identified USP1 and Vimentin as downstream targets of HuR in post-transcriptional regulation, mediating the effects of circUSP1. The parent gene USP1 also enhanced the viability and mobility of GC cells. Additionally, tissue-derived circUSP1 could serve as an independent prognostic factor for GC, while plasma-derived circUSP1 showed promise as a diagnostic biomarker, outperforming conventional markers including serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA19-9). Our study highlights that circUSP1 promotes GC progression by binding to and stabilizing oncogenic HuR, thereby facilitating the upregulation of USP1 and Vimentin at the post-transcriptional level. These findings suggest that circUSP1 could be a potential therapeutic target and a diagnostic and prognostic biomarker for GC.

Serum tumor markers expression (CA199, CA242, and CEA) and its clinical implications in type 2 diabetes mellitus.

Glucose and lipid metabolic disorder in patients with type 2 diabetes mellitus (T2DM) is associated with the levels of serum tumor markers of the digestive tract, such as cancer antigen (CA)199. Therefore, tumor markers in T2DM are important. To evaluate the expression of serum tumor markers [CA199, CA242, and car-cinoembryonic antigen (CEA)] and the clinical implications of the expression in T2DM. For this observational study conducted at Hefei BOE Hospital, China, we enrolled 82 patients with first-onset T2DM and 51 controls between April 2019 and December 2020. Levels of fasting blood glucose (FBG), tumor markers (CA199, CEA, and CA242), glycosylated hemoglobin (HbA1c), etc. were measured and group index levels were compared. Moreover, FBG and HbA1c levels were correlated with tumor marker levels. Tumor markers were tested for diagnostic accuracy in patients with > 9% HbA1c using the receiver operating curve (ROC) curve. The T2DM group had high serum FBG, HbA1c, CA199, and CEA levels (P < 0.05). A comparative analysis of the two groups based on HbA1c levels (Group A: HbA1c ≤ 9%; Group B: HbA1c > 9%) revealed significant differences in CEA and CA199 levels (P < 0.05). The areas under the ROC curve for CEA and CA199 were 0.853 and 0.809, respectively. CA199, CEA, and CA242 levels positively correlated with HbA1c (r = 0.308, 0.426, and 0.551, respectively) and FBG levels (r = 0.236, 0.231, and 0.298, respectively). As compared to controls, serum CEA and CA199 levels were higher in patients with T2DM. HbA1c and FBG levels correlated with CA199, CEA, and CA242 levels. Patients with poorly controlled blood sugar must be screened for tumor markers.

Value of combined serum CEA, CA72-4, and CA19-9 marker detection in diagnosis of colorectal cancer.

The aim of this study was to examine whether the combination of serum tumor markers (carcinoembryonic antigen [CEA], carbohydrate antigen [CA]72-4, CA19-9) improves sensitivity and accuracy in the diagnosis of colorectal cancer and precancerous lesion tubular adenoma. An automatic electrochemiluminescence immunoassay with matched kits (ECLIA) was performed on a Roche Cobas e411 analyzer to determine the levels of serum CEA, CA72-4, and CA19-9 in 35 patients with early colorectal cancer, 87 patients with tubular adenoma, and 58healthy people undergoing colonoscopy after positive fecal immunochemical test (FIT) in a colorectal cancer screening program 2021 January to April. The values of these three tumor markers in the diagnosis of colorectal cancer and tubular adenoma were analyzed. 180 patients (92 female and 88 male) were included into the study. We compared serum CEA, CA72-4 and CA19-9 markers among 3 groups: healthy people (mean age 64,0 ±8,6), patients with tubular adenoma (mean age 62,7 ± 6,4) and colorectal cancer (mean age 59,2 ±6,2). The levels of serum CEA, CA72-4, and CA19-9 were higher in the colorectal cancer group than in the tubular adenoma group and healthy subjects, and these differences were significant (p < 0.05). The combination of CEA, CA72-4, and CA19-9had a higher diagnostic value for colorectal cancer compared to single markers, and the positive detection rate was 54.3%. The diagnostic power when using all three markers was the best, and applied for colorectal cancer and tubular adenoma. The combination of CA72-4, CEA, and CA19-9 markers increases the sensitivity and accuracy in the diagnosis of colorectal cancer and can thus be considered an important tool for early colorectal diagnosis.