Serum Carcinoembryonic Antigen Research Articles

The influence of knocking down the expression of low-density lipoprotein receptor associated proteins on the vascular abnormalities in hepatocellular carcinoma and its mechanisms

Objectives: To investigate the effect of the expression of low-density lipoprotein receptor associated protein (LDLR) on the vascular abnormalities in hepatocellular carcinoma (HCC) and its mechanisms. Methods: Based on the information of Oncomine Cancer GeneChip database, we analyzed the correlation between the expression level of LDLR and the expression level of carcinoembryonic antigen (CEA) and CD31 in hepatocellular carcinoma tissues. Lentiviral transfection of short hairpin RNA target genes was used to construct LDLR-knockdown MHCC-97H and HLE hepatocellular carcinoma cells. The differential genes and their expression level changes in LDLR-knockdown hepatocellular carcinoma cells were detected by transcriptome sequencing, real-time fluorescence quantitative polymerase chain reaction, and protein immunoblotting. The gene-related signaling pathways that involve LDLR were clarified by enrichment analysis. The effect of LDLR on CEA was assessed by the detection of CEA content in conditioned medium of hepatocellular carcinoma cells. Angiogenesis assay was used to detect the effect of LDLR on the angiogenic capacity of human umbilical vein endothelial cells, as well as the role of CEA in the regulation of angiogenesis by LDLR. Immunohistochemical staining was used to detect the expression levels of LDLR in 176 hepatocellular carcinoma tissues, and CEA and CD31 in 146 hepatocellular carcinoma tissues, and analyze the correlations between the expression levels of LDLR, CEA, and CD31 in the tissues, serum CEA, and alanine transaminase (ALT). Results: Oncomine database analysis showed that the expressions of LDLR and CEA in the tissues of hepatocellular carcinoma patients with portal vein metastasis were negatively correlated (r=-0.64, P=0.001), whereas the expressions of CEA and CD31 in these tissues were positively correlated ( r=0.46, P=0.010). The transcriptome sequencing results showed that there were a total of 1 032 differentially expressed genes in the LDLR-knockdown group and the control group of MHCC-97H cells, of which 517 genes were up-regulated and 515 genes were down-regulated. The transcript expression level of CEACAM5 was significantly up-regulated in the cells of the LDLR-knockdown group. The Gene Ontology (GO) function enrichment analysis showed that the differential genes were most obviously enriched in the angiogenesis function. The Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis showed that the relevant pathways involved mainly included the cellular adhesion patch, the extracellular matrix receptor interactions, and the interactions with the extracellular matrix receptors. The CEA content in the conditioned medium of the LDLR-knockdown group was 43.75±8.43, which was higher than that of the control group (1.15±0.14, P＜0.001). The results of angiogenesis experiments showed that at 5 h, the number of main junctions, the number of main segments, and the total area of the lattice formed by HUVEC cells cultured with the conditioned medium of MHCC-97H cells in the LDLR-knockdown group were 295.3±26.4, 552.5±63.8, and 2 239 781.0±13 8211.9 square pixels, which were higher than those of the control group (113.3±23.5, 194.8±36.5, and 660 621.0±280 328.3 square pixels, respectively, all P＜0.01).The number of vascular major junctions, the number of major segments, and the total area of the lattice formed by HUVEC cells cultured in conditioned medium with HLE cells in the LDLR-knockdown group were 245.3±42.4, 257.5±20.4, and 2 535 754.5±249 094.2 square pixels, respectively, which were all higher than those of the control group (113.3±23.5, 114.3±12.2, and 1 565 456.5±219 259.7 square pixels, respectively, all P＜0.01). In the conditioned medium for the control group of MHCC-97H cells,the number of main junctions, the number of main segments, and the total area of the lattice formed by the addition of CEA to cultured HUVEC cells were 178.9±12.0, 286.9±12.3, and 1 966 990.0±126 249.5 spixels, which were higher than those in the control group (119.7±22.1, 202.7±33.7, and 1 421 191.0±189 837.8 square pixels, respectively). The expression of LDLR in hepatocellular carcinoma tissues was not correlated with the expression of CEA, but was negatively correlated with the expression of CD31 (r=-0.167, P=0.044), the level of serum CEA (r=-0.061, P=0.032), and the level of serum ALT(r=-0.147,P=0.05). The expression of CEA in hepatocellular carcinoma tissues was positively correlated with the expression of CD31 (r=0.192, P=0.020). The level of serum CEA was positively correlated with the level of serum ALT (r=0.164, P=0.029). Conclusion: Knocking down LDLR can promote vascular abnormalities in HCC by releasing CEA.

Evaluation of the value of combined detection of tumor markers CA724, carcinoembryonic antigen, CA242, and CA19-9 in gastric cancer.

Gastric cancer is a global health concern that poses a significant threat to human well-being. To detecting serum changes in carcinoembryonic antigen (CEA), carbohydrate antigens (CA) 724, CA242, and CA19-9 expression among patients with gastric cancer. Eighty patients diagnosed with gastric cancer between January 2020 and January 2023 were included in the observation group, while 80 patients with benign gastric diseases were included in the control group. Both groups were tested for tumor markers (CA724, CEA, CA242, and CA19-9]. Tumor marker indicators (CA724, CEA, CA242, and CA19-9) were compared between the two groups, assessing positive rates of tumor markers across various stages in the observation group. Additionally, single and combined detection of various tumor markers were examined. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value observed for the combined detection of CA724, CEA, CA242, and CA19-9 were higher than those of CA724, CEA, CA242, and CA19-9 individually. Therefore, the combined detection of CA724, CEA, CA242, and CA19-9 has a high diagnostic accuracy and could reduce the occurrence of missed or misdiagnosed cases, facilitating the early diagnosis and treatment of patients. CA724, CEA, CA242, and CA19-9 serum levels in gastric cancer patients significantly surpassed those in non-gastric cancer patients (P < 0.05). Their combined detection can improve the diagnostic accuracy for gastric cancer, warranting clinical promotion.

The efficacy and safety of continuous intravenous infusion of rh-endostatin combined with platinum-based doublet chemotherapy for advanced non-small-cell lung cancer.

Platinum-based doublet chemotherapy is commonly used in the treatment of non-small cell lung cancer (NSCLC). A growing body of evidence indicates that incorporating antiangiogenic agents into platinum-based chemotherapy may enhance the survival outcomes for NSCLC patients. However, the optimal administration protocol for intravenous recombinant human endostatin (rh-endostatin), an antiangiogenic agent, remains uncertain at present. This study aims to investigate the efficacy and safety of 5-d continuous intravenous infusion of rh-endostatin in combination with chemotherapy for patients with advanced NSCLC. The predictive biomarkers for this treatment regimen were further probed. This prospective, single-arm multicenter study enrolled a total of 48 patients with advanced NSCLC who were histologically or cytologically confirmed but had not received any prior treatment from January 2021 to December 2022. Prior to the chemotherapy, these patients received a continuous intravenous infusion of rh-endostatin (210mg) over a period of 120h, using an infusion pump. The chemotherapy regimen included a combination of platinum with either pemetrexed or paclitaxel, given in 21-day cycles. The primary endpoint of the study was median progression-free survival (mPFS), and the secondary endpoints included median overall survival (mOS), objective response rate (ORR), disease control rate (DCR), and assessment of adverse events (AEs). The mPFS was 6.5 months (95% confidence interval (CI): 3.8-9.1m) while the mOS was 12.3 months (95% CI: 7.6-18.5m). The ORR and DCR was 52.1% and 75.0%, respectively. Leukopenia (52.1%), anemia (33.3%), and thrombocytopenia (20.8%) were the most common adverse effects and these toxicities were deemed acceptable and manageable. In addition, a correlation was noted between elevated serum carcinoembryonic antigen (CEA) levels and decreased PFS and OS. The incorporation of a 5-day continuous intravenous infusion of rh-endostatin into platinum-based doublet chemotherapy has demonstrated both safety and efficacy in the treatment of advanced NSCLC. Furthermore, the baseline serum levels of CEA may potentially function as a predictor for the efficacy of rh-endostatin when combined with chemotherapy in NSCLC patients. GOV: NCT05574998.

A comparative analysis of serum NSE, LDH and CEA levels in lung cancer and extrapulmonary malignancies

A comparative analysis of serum NSE, LDH and CEA levels in lung cancer and extrapulmonary malignancies

Prevalence of serum CEA and CA 19-9 elevation in patients with colorectal cancers at The Nairobi Hospital, Kenya

Prevalence of serum CEA and CA 19-9 elevation in patients with colorectal cancers at The Nairobi Hospital, Kenya

Pathological Pleural Invasion is a Risk Factor for Late Recurrence in Long-Term Survivors of Non-small Cell Lung Cancer after Complete Resection.

Information regarding late recurrence after pulmonary resection for non-small cell lung cancer (NSCLC) is limited. This study aimed to analyze the risk factors for late recurrence after surgery for NSCLC in the current era. We conducted a retrospective study of patients who underwent complete resection for pathological I-III NSCLC between 2006 and 2015. Late recurrence was defined as a recurrence that met the following conditions: (1) the patient underwent chest computed tomography (CT) at or after 54 months after surgery and recurrence was not detected at that time, and (2) recurrence that occurred more than 5 years after surgery. The factors influencing late recurrence, relapse-free survival (RFS), and overall survival (OS) after surgery were analyzed. A total of 1275 with 5-year relapse-free survival after surgery were enrolled in this study. The mean age of the patients was 66.4 years and 54% of the patients were men. The median interval between surgery and the latest follow-up examination was 98 months. In total, 35 patients (2.7%) experienced late recurrence and 138 patients have died thus far. The cumulative recurrence, RFS, and OS rates at 10 years were 3.9%, 84.9%, and 86.3%, respectively. A multivariate analysis revealed that pleural invasion was an independent risk factor for late recurrence. Pleural invasion was a poor prognostic factor for both RFS and OS. Pleural invasion was a predictor of late recurrence. Age>67 years, preoperative serum carcinoembryonic antigen (CEA)>5 ng/ml, non-adenocarcinoma, and pleural invasion were poor prognostic factors for RFS.

Implications of Pretreatment Serum Carcinoembryonic Antigen Levels and Perineural Invasion with Staging, Prognosis, and Management in Stage I-III Colon Cancer after Surgery: A Retrospective Cohort Study in the SEER Database.

Pretreatment levels of serum carcinoembryonic antigen (CEA) and perineural invasion (PNI) are related to poor prognosis in colon cancer. We analyzed the CEA and PNI (defined as incorporation of carcinoembryonic antigen and perineural invasion (CP)-stage), which are included in the Tumor-Node-Metastasis (TNM) staging system of the American Joint Committee on Cancer (AJCC), and evaluated the survival prognosis of patients treated with surgery in I-III stage colon carcinoma. We employed a retrospective study for eligible colon carcinoma patients obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. Kaplan-Meier curve and Multivariate Cox regression analysis were used to analyze different TNM-CP stages for the cancer-specific survival (CSS) probabilities in colon cancer. In our study, CEA levels and PNI were significant prognostic factors (p < 0.05), and the newly proposed CP-stage was an independent prognostic index in stage I-III colon carcinoma after surgery. Multivariate Cox regression analyses indicated that CP1-stage was related to a 63.9% increased risk of cancer-specific mortality (hazard ratio (HR): 1.639, 95% confidence interval (CI): 1.544-1.739, p < 0.001), compared with CP0-stage in colon cancer. In respective TNM stages, the CP0-stage had an advantage over the CP1-stage for CSS (p < 0.001). Moreover, CP1-stage patients with node-negative colon cancer were contacted with similar or worse survival in comparison to CP0-stage patients with node-positive. For postoperative patients with stage I-III colon cancer, our study indicated that the CP stage is a significant prognostic factor for CSS, which deserves more clinical attention. It's worth noting that including the CP stage in the AJCC TNM staging system of colon carcinoma is beneficial to the survival prediction and clinical treatment.

Expression and prognostic significance of KAP1 gene in malignant pleural mesothelioma

Objective: To explore the expression of KAP1 (KRAB-associated protein 1, KAP1) in Malignant pleural mesothelioma (MPM) based on the cancer genome atlas (TCGA) and clinical trials. And elucidate the correlation between the expression of KAP1 and the clinical pathological parameters of patients with MPM and its prognosis. Methods: In April 2022, Based on the second generation KAP1mRNA sequencing data and clinicopathological data of MPM patients downloaded from TCGA database, the correlation between KAP1mRNA expression and clinical parameters was analyzed, and the correlation between KAP1 protein expression and clinicopathological parameters and its prognostic value were analyzed based on Chuxiong data set cohort clinical samples. The expression of KAP1 mRNA in MPM samples and matched normal tumor adjacent tissues was detected by qRT-PCR, and the expression of KAP1 protein in MPM and normal pleural tissues was detected by immunohistochemistry and Westernblotting. To construct a Kaplan-Meier model to explore the effect of KAP1 expression on the prognosis of MPM patients, and to analyze the prognostic factors of MPM patients by Cox regression. Results: qRT-PCR and Western blotting detection showed that the expression levels of KAP1 gene in four different MPM cells (NCI-H28, NCI-H2052, NCI-H2452, and MTSO-211H) were significantly higher than those in normal pleural mesothelial cells Met-5A. qRT-PCR, Western blotting and IHC results demonstrated that the mRNA and protein expression levels of KAP1 in MPM tissues was significantly higher than that in matching normal mesothelial tissues, and the expression level of KAP1 protein was correlated with TP 53 protein expression levels and serum CEA levels (P<0.05) . The mRNA expression level was significantly correlated with the prognosis, The overall survival time of mesothelioma patients with high KAP1mRNA expression was significantly shorter (HR=3.7, Logrank P<0.001) . Tumor type, age and the mRNA expression were related to the prognosis of MPM patients (P<0.05) . Multivariate analysis showed that tumor type and KAP1 mRNA expression level were independent prognostic factors of MPM patients (P<0.05) . Conclusion: In this study, TCGA database and Chuxiong cohort experiment samples were used to collect the relevant information of KAP1 expression in malignant melanoma tissues. It was confirmed that KAP1 is highly expressed in MPM tissues. The mRNA expression level and pathological type are correlated with the prognosis of patients.

Presence of CD44v9-Expressing Cancer Stem Cells in Circulating Tumor Cells and Effects of Carcinoembryonic Antigen Levels on the Prognosis of Colorectal Cancer.

Circulating tumor cells (CTCs) are cancer cells released from the primary tumor into the bloodstream, and contain cancer stem cells that influence tumor survival, recurrence, and metastasis. Here, we investigated CD44v9 expression in CTCs and impact of preoperative carcinoembryonic antigen (CEA) levels on colorectal cancer (CRC) prognosis. We analyzed the expression of CD44v9 mRNA in CTCs using reverse transcription-polymerase chain reaction and preoperative CEA levels in blood samples obtained from 300 patients with CRC. Subsequently, we evaluated the association of CD44v9 expression and CEA levels with clinicopathological factors. CD44v9 mRNA was expressed in 31.3% of the patients, and was significantly associated with liver metastasis. Patients with positive CD44v9 expression had a lower 5-year survival rate (62.3%) than those with negative CD44v9 expression (82.8%, p < 0.001). Cox regression analysis identified CD44v9 expression and high CEA levels (≥5 ng/mL) as poor prognostic factors, while negative CD44v9 expression and low CEA levels (<5 ng/mL) were associated with favorable prognosis (hazard ratio = 0.285, p = 0.006). These results suggest that a combination of CD44v9 mRNA expression in CTCs and serum CEA levels could serve as a valuable prognostic marker for CRC, potentially enhancing the accuracy of prognosis predictions.

Spontaneous Remission of Minimal Change Disease in a Colon Cancer Patient: A Case Report.

Minimal change disease (MCD) is most often primary but may occur secondary to other systemic diseases such as malignancy. In secondary MCD, spontaneous remission of nephrotic syndrome after the treatment of related diseases without steroid therapy is rare. A 78-year-old man visited the outpatient clinic with foamy urine and generalized edema that had persisted for 2 months. The patient had nephrotic syndrome. Before a kidney biopsy, he underwent several tests to determine the secondary cause of the nephrotic syndrome. The serum CEA was slightly elevated, and colon cancer was detected in the sigmoid colon. MCD was diagnosed from a kidney biopsy. He immediately underwent surgery for colon cancer. Complete remission of the MCD was achieved within 2 weeks after surgery. Here, we report a rare case of a patient with secondary MCD who successfully achieved spontaneous remission after colon cancer surgery.

Long-term outcomes of intraoperative chemotherapy with 5-FU for colorectal cancer patients receiving curative resection (IOCCRC): a randomized, multicenter, prospective, phase III trial.

We aimed to compare combined intraoperative chemotherapy and surgical resection with curative surgical resection alone in colorectal cancer patients. We performed a multicenter, open-label, randomized, phase III trial. All eligible patients were randomized and assigned to intraoperative chemotherapy and curative surgical resection or curative surgical resection alone (1:1). Survival actualization after long-term follow-up was performed in patients analyzed on an intention-to-treat basis. From January 2011 to January 2016, 696 colorectal cancer patients were enrolled and randomly assigned to intraoperative chemotherapy and radical surgical resection (n=341) or curative surgical resection alone (n=344). Intraoperative chemotherapy with surgical resection showed no significant survival benefit over surgical resection alone in colorectal cancer patients (3-year DFS: 91.1% vs. 90.0%, P=0.328; 3-year OS: 94.4% vs. 95.9%, P=0.756). However, colon cancer patients benefitted from intraoperative chemotherapy, with a relative 4% reduction in liver and peritoneal metastasis (HR=0.336, 95% CI: 0.148-0.759, P=0.015) and a 6.5% improvement in 3-year DFS (HR=0.579, 95% CI: 0.353-0.949, P=0.032). Meanwhile, patients with colon cancer and abnormal pretreatment CEA levels achieved significant survival benefits from intraoperative chemotherapy (DFS: HR=0.464, 95% CI: 0.233-0.921, P=0.029 and OS: (HR=0.476, 95% CI: 0.223-1.017, P=0.049). Intraoperative chemotherapy showed no significant extra prognostic benefit in total colorectal cancer patients who underwent radical surgical resection; however, in colon cancer patients with abnormal pretreatment serum CEA levels (> 5ng/ml), intraoperative chemotherapy could improve long-term survival.

Serum Biochemical Markers for Medullary Thyroid Carcinoma: An Update.

Medullary thyroid carcinoma (MTC), a rare malignancy, requires early diagnosis for optimal patient outcomes. An important aspect of MTC diagnosis is the assessment of serum biomarkers. This review aimed to evaluate the use of serum biomarkers in the diagnosis, prognosis, and follow-up of MTC. A thorough search of PubMed covering 1975 to 2022 was conducted to identify English-language articles on MTC serum biomarkers. The review revealed that calcitonin (Ctn) and carcinoembryonic antigen (CEA) remain the most important serum biomarkers for MTC diagnosis and management. Despite limited studies on procalcitonin (PCT), its stability and ability to exclude interference from inflammation make it a valuable potential marker of MTC. Although the positive rate of serum CA19-9 levels in MTC patients was not high, it can be used as an indicator of poor prognosis in advanced MTC. Other serum markers, including chromogranin A, gastrin-releasing peptide precursor, and neurospecific enolase, did not show any unique value in MTC diagnosis and management. Taken together, this review emphasized the importance of serum biomarkers, particularly Ctn and CEA, in the diagnosis and management of MTC. PCT shows promise as a valuable potential marker, whereas CA19-9 can be used as a prognostic indicator of advanced MTC. Further research is needed to validate the significance of these serum biomarkers in MTC and determine the effects of confounding factors on their levels. Clinicians should consider using these markers in MTC diagnosis, prognosis, and follow-up, particularly for patients with advanced disease.

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

Objective: 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.&#x0D; Methods: 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.&#x0D; Results: The positive rates of CEA, CA125 and SP70 antigen in pleural effusion were higher in the malignant group than in the benign group (p&gt;0.05); The positive rates of CEA and CA125 in the malignant group were higher than those in the benign group (p&gt;0.05), with no statistically significant difference between the two groups in the positive rates of SP70 antigen (p&gt;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&gt;0.05).&#x0D; Conclusion: 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.&#x0D; doi: https://doi.org/10.12669/pjms.40.5.7956&#x0D; How to cite this: Yan W, Li Y, Peng Z. Clinical value of combined detection of Carcinoembryonic Antigen and CA125 in the diagnosis of non-small cell lung cancer combined with Malignant Pleural Effusion. Pak J Med Sci. 2024;40(5):---------. doi: https://doi.org/10.12669/pjms.40.5.7956&#x0D; This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.