Carbohydrate Antigen Research Articles

Hepatic methotrexate-associated lymphoproliferative disease: a case report and literature review.

Methotrexate-associated lymphoproliferative disease (MTX-LPD) is a rare and life-threatening complication of MTX administration. MTX-LPD features more extranodal lesions than malignant lymphoma; however, the liver is an extremely rare organ that develops LPD. Herein, we present a case of hepatic MTX-LPD treated with surgical resection. We also reviewed the literature on hepatic MTX-LPD. A 66-year-old man with a history of rheumatoid arthritis (RA) was admitted to our department for the treatment of hepatic solitary liver tumor. The patient had been receiving MTX (14mg/week) for RA for 6years. MTX was withdrawn and salazosulfapyridine was prescribed 3weeks prior to admission because of mediastinal MTX-LPD. Abdominal contrast-enhanced computed tomography showed a slightly ring-like enhanced hypovascularized mass (80mm) in the lateral section of the liver. Carbohydrate antigen 19-9 (78.1U/mL) level was elevated. No evidence was observed on esophagogastroduodenoscopy or colonoscopy. The tumor was suspected to be an intrahepatic cholangiocarcinoma. The patient underwent hepatic lateral sectionectomy and lymphadenectomy. Pathological examination revealed that the hepatic mass was coagulative necrosis of the CD20-positive B-cell lymphocytes. These histological findings were similar to those of rapid necrotic lymphoma. MTX-LPD is known to spontaneously regress after withdrawing MTX, and the patient was diagnosed with hepatic MTX-LPD. MTX-LPD can occur in the liver. Clinician should suspect hepatic MTX-LPD when a liver mass is detected in patient who had been treating with MTX for RA.

ASO Visual Abstract: Neoadjuvant Treatment with Changes in Chemotherapy Regimens According to Carbohydrate Antigen 19-9 Level for Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma.

ASO Visual Abstract: Neoadjuvant Treatment with Changes in Chemotherapy Regimens According to Carbohydrate Antigen 19-9 Level for Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma.

MS O12 - HPB The efficacy of CA19-9 in predicting resectability and survival in pancreatic cancer patients with jaundice: A retrospective cohort study

Abstract Background Carbohydrate antigen 19-9 (CA19-9) is the most utilised biochemical marker in pancreatic ductal adenocarcinoma (PDAC); shown to be related to resectability and prognosis. However, concurrent cholestasis, commonly seen in PDAC, can also elevate CA19-9, which may lead to unreliability and hence limit its efficacy in jaundiced patients, making management planning and prognostication more challenging. This study aims to investigate the impact of jaundice on the efficacy of CA19-9 in predicting resectability and survival in PDAC patients. Method 715 patients undergoing attempted resection for PDAC between 2010-2023 were identified from a prospectively maintained surgical database for retrospective analysis. The ability of CA19-9 to predict resectability and survival in different bilirubin sub-groups was assessed using receiver operating characteristic and Kaplan-Meier curves. Existing adjustment methodologies were applied and the curves replotted to assess their effects on the predictive efficacy of CA19-9. Multivariate analysis was then utilised to screen other potentially predictive factors which could be incorporated in the future. Results Of the 554 (77.4%) patients who underwent resection, CA19-9 predicted resectability in the first three bilirubin subgroups: ≤21 µmol/l (AUROC:0.660, 95% CI:0.551-0.769, p=0.004), 21<x≤130 µmol/l (AUROC:0.689, 95% CI:0.595-0.784, p<0.001) and 130<x≤315 µmol/l (AUROC:0.710, 95% CI:0.614-0.807, p<0.001). However, CA19-9 did not predict resectability in patients with bilirubin levels >315 µmol/l (AUROC:0.579, 95% CI:0.452-0.707, p=0.222). CA19-9 was a significant predictor of overall survival in the non-jaundiced (p=0.048) cohort but did not predict survival in patients with bilirubin levels >21 µmol/l. Existing adjustment methodologies did not improve predictive efficacy of CA19-9 for resectability or prognosis. Conclusion These findings support the prospect of decreased ability of CA19-9 to predict resectability and survival in PDAC patients with jaundice. Further investigation is required to find a method of adjusting CA19-9 values based on jaundice to aid diagnostic and treatment decision making.

Comprehensive data of 5085 patients newly diagnosed with colorectal liver metastasis between 2013 and 2017: Fourth report of a nationwide survey in Japan.

The Joint Committee for Nationwide Survey on colorectal liver metastasis (CRLM) was established to improve treatment outcomes in patients with CRLM. The aim of this study was to evaluate the transition in the characteristics and treatment strategies of patients with CRLM and to analyze the prognostic factors. The data of 5085 patients newly diagnosed between 2013 and 2017 were compared with those of 3820 patients from 2005 and 2007. In patients who underwent hepatectomy (n = 2759 and 2163), the number of CRLMs was significantly higher and in the 2013-2017 data than in the 2005-2007 data (median 2 vs. 1; p = .005). Overall survival (OS) rates after diagnosis of CRLM after hepatectomy were better in the 2013-2017 data than that in the 2005-2007 data (5-year OS, 62.4% vs. 56.7%, p < .001). Recurrence-free survival (RFS) after hepatectomy was comparable between the groups (5-year RFS, 30.5% vs. 30.7%; p = .068). Multivariate analyses identified age at diagnosis of CRLM ≥70 years, lymph node metastasis of primary lesion, preoperative carbohydrate antigen (CA) 19-9 value >100 U/mL, number of CRLM 2-4, and R2 resection as independent predictors of OS. Synchronous CRLM, concomitant extrahepatic metastasis, lymphatic invasion, lymph node metastasis of primary lesion, preoperative CA19-9 value >100 U/mL, number of CRLM 5-, and nonlaparoscopic approach were selected as that of RFS. Despite having a higher prevalence of advanced stage CRLM in the 2013-2017 patient population compared to the 2005-2007 cohort, prognostic outcomes demonstrably improved in the later period.

Preoperative Prediction of Perineural Invasion in Pancreatic Ductal Adenocarcinoma Using Machine Learning Radiomics Based on Contrast-Enhanced CT Imaging.

The objective of the study is to assess the clinical value of machine learning radiomics based on contrast-enhanced computed tomography (CECT) images in preoperative prediction of perineural invasion (PNI) status in pancreatic ductal adenocarcinoma (PDAC). A total of 143 patients with PDAC were enrolled in this retrospective study (training group, n = 100; test group, n = 43). Radiomics features were extracted from CECT images and selected by the Mann-Whitney U-test, Pearson correlation coefficient, and least absolute shrinkage and selection operator (LASSO). The logistic regression (LR), support vector machine (SVM), random forest (RF), extreme gradient boosting (XGBoost), and decision tree (DT) algorithms were trained to build radiomics models by radiomic features. Multivariate logistic regression was employed to identify independent predictors and establish clinical models. A combined model was constructed by integrating clinical and radiomics features. Model performances were assessed by receiver operating characteristic curves (ROCs) and decision curve analyses (DCAs). A total of 788 radiomics features were extracted from CECT images, of which 14 were identified as significant through the three-step selection process. Among the machine learning models, the SVM radiomics model exhibited the highest predictive performance in the test group, achieving an area under the curve (AUC) of 0.831, accuracy of 0.698, sensitivity of 0.677, and specificity of 0.750. After logistic regression screening, the clinical model was established using carbohydrate antigen 19-9 (CA199) levels as one independent predictor. In the test group, the clinical model demonstrated an AUC of 0.644, accuracy of 0.744, sensitivity of 0.871, and specificity of 0.417. The combined model showed improved performance compared to both the clinical and radiomics models in the test group, with an AUC of 0.844, accuracy of 0.767, sensitivity of 0.806, and specificity of 0.667. Subsequently, DCA of the combined model indicated optimal clinical value for predicting PNI status. Machine learning radiomics models can accurately predict PNI status in patients with pancreatic ductal adenocarcinoma. The combined model, which incorporates clinical and radiomics features, enhances preoperative diagnostic performance and aids in the selection of treatment methods.

Ultrashort Cell-Free DNA Fragments and Vimentin-Positive Circulating Tumor Cells for Predicting Early Recurrence in Patients with Biliary Tract Cancer.

Background/Objectives: Biliary tract cancer (BTC) is a rare but aggressive malignancy that requires surgical treatment. However, postoperative recurrence rates are high, and reliable predictors of recurrence are limited. This study aimed to investigate the effectiveness of cell-free DNA (cfDNA) and circulating tumor cells (CTCs) in predicting early recurrence after curative surgery and complete adjuvant therapy in patients with BTC. Methods: Twenty-four patients who underwent R0 and R1 resections and completed adjuvant therapy for BTC between September 2019 and March 2022 were followed up until March 2024. Patients were categorized into early recurrence (ER) and non-ER groups, using one year as the cutoff for recurrence. Results: The combination score derived from ultrashort fragments of cfDNA, vimentin-positive CTCs, and carbohydrate antigen (CA) 19-9 levels showed a statistically significant difference between the ER and non-ER groups (p-value < 0.001). The receiver operating characteristic curve from the combination score and CA 19-9 levels yielded areas under the curve of 0.891 and 0.750, respectively. Conclusions: Although further research is required, these findings suggest that cfDNA and CTCs may increase the accuracy of predicting postoperative recurrence in patients with BTC.

Optical immunosensor panel using quantum dot-antibody conjugates for highly sensitive detection of carbohydrate antigen 19-9 (CA19-9)

Optical immunosensor panel using quantum dot-antibody conjugates for highly sensitive detection of carbohydrate antigen 19-9 (CA19-9)

Survival Outcomes According to NCCN Criteria for Resection Following Neoadjuvant Therapy for Patients with Localized Pancreatic Cancer.

This study aimed to assess the prognostic value of the National Comprehensive Cancer Network (NCCN) criteria for resection following neoadjuvant therapy for patients with localized pancreatic ductal adenocarcinoma (PDAC). This retrospective single-center study assessed 193 consecutive patients with localized PDAC (104 males and 89 females; mean age, 61.1 ± 9.4 years) who underwent neoadjuvant therapy followed by surgery between January 2010 and March 2021. Combined resectability and carbohydrate antigen (CA) 19-9 evaluation before and after neoadjuvant therapy was used to determine whether patients were eligible for resection according to the NCCN criteria. Post-surgical overall survival (OS), recurrence free survival (RFS), and pathologic results were evaluated and compared between patients considered eligible according to the NCCN criteria and those considered ineligible. Preoperative factors associated with better OS and RFS also were investigated. Of the 193 patients, 168 (87.0 %) were eligible for resection according to the NCCN criteria. The patients eligible according to the NCCN criteria showed marginally longer OS than those considered ineligible (p = 0.056). After adjustment of variables, meeting the NCCN criteria for resection was an independent predictor of better OS (hazard ratio, 0.57; 95 % confidence interval, 0.34-0.96; p = 0.034). The two groups had similar RFS. Lower T-staging (T2 or less) and less lympho-vascular invasion and peri-neural invasion were noted in the patients who met the NCCN criteria (p ≤ 0.045). The patients eligible for resection according to the NCCN criteria showed a trend toward longer OS and better pathologic results than the patients considered ineligible.

Clinical significance of CA 19-9 elevation during postoperative surveillance for extrahepatic bile duct cancer: a nomogram-based approach for the prediction of short-term recurrence

BackgroundThis study aimed to assess the significance of elevated carbohydrate antigen (CA) 19-9 in postoperative surveillance of extrahepatic bile duct cancer and to identify short-term recurrence predictors. MethodsThis retrospective study included patients with elevated CA 19-9 post-curative surgery. Patients were categorized into positive and negative CT groups based on the detection of recurrence at CA 19-9 elevation. Short-term recurrence was defined as recurrence within 6 months in the negative CT group. We identified the factors associated with short-term recurrence and devised a predictive nomogram. ResultsAmong the 190 patients, 91 (47.9%) exhibited tumor recurrence with CA 19-9 elevation (CT-positive group), whereas 99 (52.1%) showed no recurrence (CT-negative group). In the CT-negative group (n=99), 22 (22.2%) experienced short-term tumor recurrence within 6 months. Preoperative CA 19-9 (odds ratio [OR]: 1.5, p=0.016), postoperative CA 19-9 (OR: 1.9, p=0.047), adjuvant treatment (OR: 3.5, p=0.032), and the absence of inflammation (OR: 3.5, p=0.045) were predictors of short-term recurrence. The area under the curve of the nomogram was 0.80 (95% CI: 0.69–0.90). DiscussionDespite elevated CA 19-9 levels, approximately 50% of patients exhibited no recurrence during postoperative surveillance for extrahepatic bile duct cancer. Factors influencing short-term recurrence encompass pre- and postoperative CA 19-9, adjuvant treatment, and inflammatory status.

Performance of DNA methylation and blood-borne tumor indicators in detecting colorectal neoplasia and adenomas: a comparative study with the fecal occult blood test.

To evaluate the performance of stool methylated syndecan2 (mSDC2), methylated septin9 (mSEPT9), fecal occult blood test (FOBT), carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125) and carbohydrate antigen 199 (CA199) in detecting colorectal neoplasia and adenomas. Blood-borne CEA, CA125, and CA199 levels were measured by electrochemiluminescence. The SDC2 methylation was detected by Methylation Detection Kit for Human SDC2 Gene (Real time PCR), and the SEPT9 methylation was detected by the Septin9 Gene Methylation Detection Kit based on PCR fluorescent probe assay. The colonoscopy combined with tissue biopsy pathology was used as a validation criterion for colorectal neoplasia. In detecting colorectal neoplasia, the AUCs of mSDC2, FOBT and mSEPT9 were 0.935 (95% CI: 0.915-0.956, P<0.001), 0.824 (95% CI: 0.617-1.000, P<0.001) and 0.671 (95% CI: 0.511-0.831, P<0.001), respectively. The sensitivity of mSDC2, FOBT and mSEPT9 were 100.0%, 66.7% and 40.0%, respectively. But the AUC of CEA, CA125 and CA199 were not statistically significant for colorectal neoplasia (all P>0.05). The combined application of mSEPT9 and mSDC2 showed the best predictive performance (AUC: 0.956, 95% CI: 0.887~1.000). For adenomas, the AUC of FOBT was extremely low (AUC: 0.524, 95% CI: 0.502-0.545, P=0.004). The CEA, CA125, CA199, mSEPT9 and mSDC2 were not statistically significant in detecting adenomas (all P>0.05). For individual tests, FOBT and mSDC2 are relatively better indicators for detecting colorectal neoplasia compared to mSEPT9, CEA, CA125 and CA199. The combined form of mSEPT9 and mSDC2 to detect colorectal neoplasia has good predictive performance. However, none of these indicators demonstrated significant predictive power for detecting adenomas in our study.

Development and validation of a tumor marker-based model for the prediction of lung cancer: an analysis of a multicenter retrospective study in Shanghai, China.

The incidence and mortality rates of cancer are the highest globally. Developing novel methodologies that precisely, safely, and economically differentiate between benign and malignant lung conditions holds immense clinical importance. This research seeks to construct a predictive model utilizing a combination of diverse biomarkers to effectively discriminate between benign and malignant lung diseases. This retrospective study included patients admitted to the two general hospitals in Shanghai from 2014 to 2015. This study was developed using five tumor markers: carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), cytokeratin fragment 21-1 (CA211), squamous cell carcinoma antigen (SCC), and neuron specific enolase (NSE). The entire sample was divided into two groups according to the hospital: 1033 cases were included in the development cohort and 300 cases in the validation cohort. Logistic regression analysis was used for univariate analysis to explore individual correlations between each selected clinical variable and lung cancer diagnostic outcome. Diagnostic prediction models were constructed and validated based on independent prognostic factors identified using multifactorial analysis. A nomogram was created using these tumor markers (age and sex were additionally included) and validated using the concordance index and calibration curves. Clinical prediction models were evaluated using decision curve analysis. Fully adjusted multivariate analysis showed that the risk of lung cancer was 2.38 times higher in men than in women. CEA positivity was associated with an 13.41-fold increased risk in lung cancer. The area under the curve (AUC) values for the development cohort and validation cohort models were 0.907 and 0.954, respectively. In the established nomogram, the AUC for the receiver operating characteristic curve was 0.907 (95% CI, 0.889-0.925). The validation model confirmed the strong discriminative power of the nomogram (AUC = 0.954). The described calibration curves demonstrated good fit predictions and observation probabilities. In addition, decision curve analysis concluded that the newly established nomogram has important implications for clinical decision making. Combined prediction models based on CEA, CA199, CA211, SCC, and NSE biomarkers could significantly the differentiation between benign and malignant lung diseases, thus facilitating better clinical decision making.

Epicardial carbohydrate antigen 125 (CA-125) levels, associated with neutrophils activity in heart failure: No differences regarding sex

Abstract Background Carbohydrate antigen 125 (CA125), is the name of the soluble part of mucin-16, after being cleaved, which is detected and increased into circulation in congestive heart failure (HF) patients. Purpose We aimed to study plasma and epicardial fat markers related to inflammation, fibrosis, adiposity, and its association with plasma and epicardial CA125 for understanding the underlying mechanisms of heart failure and the differences between men and women. Methods We have included women and men undergoing open heart surgery (n=134). Epicardial fat biopsy and blood were obtained before the procedure under signed consent. Immunohistochemistry, ELISA, multiplex-Luminex, and real-time PCR were used for analyzing protein or mRNA expression levels of CA125 and markers. Results Out of 135, 57 patients suffered heart failure (HF). CA125 was expressed on the epicardium. Their levels were positively related to neutrophils, monocytes, and fibroblasts-related markers and negatively to adiposity markers. Both, plasma and epicardial CA125 levels were increased in HF patients. In this group of patients, epicardial CA125 levels were positively associated with circulating and local neutrophil activity, measured by defensin 3 levels. After testing all markers between women and men in HF patients, we observed similar levels in plasma and epicardial CA125. However, higher plasma and epicardial adiposity markers and lower mesothelial marker ITLN-1 were detected in women than in men. Conclusion CA125 is expressed in epicardial cells and its higher levels in HF might explain the higher detected levels in plasma. Its association with local and peripheral neutrophils-related markers with CA125 suggests its common pathophysiological mechanism in women and men. However, high plasma and epicardial adiposity and low mesothelial marker ITNL-1 in epicardium in women might explain the differential mechanism in HF.

Ultrasensitive ECL immunoassay for CA15-3 via self-enhanced L012-loaded ZnNi-MOF as an emitter and CeO2–Pt as a co-reaction accelerator

Improvement in the sensitivity and accuracy of ECL-based biosensors, to a great extent, depends on the fabrication of high-performance electrochemiluminescence (ECL) sensors. Herein, polyethyleneimine (PEI)-grafted bimetallic ZnNi metal-organic framework (ZnNi-MOF/PEI) nanospheres were synthesized to prepare a L012-based ECL immunosensor for detecting carbohydrate antigen 15-3 (CA15-3). The introduced PEI was utilized not only as a bridging element for L012 luminophore and detection antibody (Ab2) immobilization but also as a co-reactant for generating the self-enhanced ZnNi-MOF/PEI-L012@Ab2 ECL signal probe. Furthermore, Pt nanoparticle-functionalized CeO2 nanorods (CeO2–Pt) featuring high-efficiency electrocatalytic properties, as a co-reaction accelerator, could catalyze H2O2 to generate abundant reactive oxygen species (ROS), further augmenting the ECL signal of ZnNi-MOF/PEI-L012@Ab2. In the presence of CA15-3 antigen, the capture antibody (Ab1)-conjugated CeO2–Pt complex (CeO2–Pt@Ab1) and ZnNi-MOF/PEI-L012@Ab2 would get closer to each other, with the formation of a “signal-on” sandwich-type ECL immunosensor. The ZnNi-MOF-assisted ECL biosensor achieved a detection limit of down to 5.75✕10−5 U mL−1. This work shows distinguished potential for measuring low levels of biomarkers that may help in the clinical diagnosis of breast cancer.

Elevated cancer biomarkers in patients with severe heart failure could be a potential predictor of mortality during LVAD support

Abstract Introduction Owing to increasing numbers of heart failure patients a search for new biomarkers predicting prognosis is desirable. Background The purpose of this study was to analyze levels of cancer biomarkers in patients with severe heart failure before or after left ventricular assist device (LVAD) implantation and estimate its impact on survival during LVAD support. Methods We retrospectively analyzed data of all consecutive 168 LVAD recipients (92.8%- male, mean age 53.3 years ( median - 56.6, SD 12.0 ), median INTERMACS profile- 3.0, ischemic etiology of heart failure- 52.4%, 41.0% post CRT-D and 54.8% post ICD implantation, 36.9 post IABP, 5.4% post ECMO%, 11.9% post CABG and 8.9% post other cardiac surgery before LVAD implantation) implanted with continuous-flow LVAD (59.5%-HeartMate3, 35.1%- HeartWare, 5.4%-Heart Mate II) in our institution within years 2009-2023. Among comorbidities 63% of patients had atrial fibrillation or flutter, 41.6%- diabetes, 37.5%- arterial hypertension, 48.8%-renal failure, 7.1% pulmonary obstructive disease, 56.5% had pulmonary hypertension with mean pulmonary artery pressure above 25 mm Hg in right heart catheterization and 47% of patients had a history of cardiac arrest or sustained ventricular arrythmia before LVAD implantation. The overall mortality was 44.0 %. 31% patients were transplanted during LVAD support and in 4 patients (2.3%) LVAD was explanted or deactivated. Patient were followed to death, heart transplantation, LVAD explantation or the end of observation in our institution. Mean time of LVAD support was 885 days (1-2570). 23% of patients had right ventricular failure (RVF) early post LVAD implantation while 7.7% had late form of RVF. Results Serum concentrations of cancer biomarkers: carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19-9, carbohydrate antigen(CA)-125 and alpha fetoprotein (AFP) taken before (56 patients -33.3%) or after (24 patients-14.3%) LVAD implantation were analyzed. Mean values, rate of abnormal results and correlation of abnormal results of CEA, CA19-9, CA-125, AFP with mortality during LVAD support were depicted in Table 1. No statistically significant correlations were found between levels of abovementioned cancer biomarkers and mortality though a trend towards increased mortality could be observed for abnormal results of CEA and Ca 19-9 taken before LVAD implantation. No malignant neoplasms were found in all analyzed patients except of one in whom a recurrence of lymphoma was found 2 months after LVAD implantation. Conclusions Patients with severe heart failure before and after LVAD implantation may present abnormal values of cancer biomarkers despite no found neoplasms. Our observation suggests that elevated cancer biomarker levels could predict mortality in heart failure patients after LVAD implantation. Further research is needed to confirm this thesis and investigate mechanisms of this phenomenon.

Construction of a diagnostic nomogram model for lymph node metastasis in gastric cancer based on human cartilage glycoprotein-39, carbohydrate antigen 50, and serum ferritin

Construction of a diagnostic nomogram model for lymph node metastasis in gastric cancer based on human cartilage glycoprotein-39, carbohydrate antigen 50, and serum ferritin

Visceral Obesity and a High Glasgow Prognostic Score Are Key Prognostic Factors for Metastatic Colorectal Cancer Treated with First Line Chemotherapy.

The prognostic significance of a high visceral fat area (VFA) in metastatic colorectal cancer (mCRC) remains unclear. We evaluated the prognostic impact of high-VFA on the long-term outcomes of patients with mCRC who underwent chemotherapy. Ninety patients with metastatic CRC who underwent chemotherapy were included. VFA measurement was performed by pre-treatment computed tomography using image analysis system. Overall survival (OS) and progression-free survival (PFS) rates were analyzed using the Cox proportional hazards model and Kaplan-Meier curves with the log-rank test. High-VFA was identified in 39 patients. The OS (2-year OS rates: 51.6% vs 33.3%, p=0.0023) and PFS rates (2-year PFS rates: 18.0% vs 2.7%, p=0.012) were significantly lower in the high-VFA group than in the low-VFA group. In multivariate analysis, the independent significant predictors of OS were carbohydrate antigen 19-9 (CA19-9) ≥37.0 U/mL (HR: 1.99, 95%CI [1.20-3.31], p=0.007), Glasgow prognostic score (GPS) of 1 or 2 (HR: 2.65, 95%CI [1.53-4.58], p<0.001), and high-VFA (HR: 3.09, 95%CI [1.81-5.25], p<0.001). Similarly, the independent significant predictors of PFS were CA19-9 ≥37.0 U/mL (HR: 2.02, 95%CI [1.21-3.38], p=0.007), GPS of 1 or 2 (HR: 1.87, 95%CI [1.17-2.99], p=0.008), and high-VFA (HR: 2.65, 95% CI [1.61-4.35], p<0.001). We demonstrated that pre-treatment high-VFA and high-GPS were significantly associated with worse OS and PFS rates in patients with mCRC who underwent chemotherapy.

Solid-phase electrochemiluminescence immunosensing platform based on bipolar nanochannel array film for sensitive detection of carbohydrate antigen 125.

Development of simple solid-phase electrochemiluminescence (ECL) immunosensor with convenient fabrication for high-performance detection of tumor biomarkers is crucial. Herein, a solid-phase ECL immunoassay was constructed based on a bipolar silica nanochannel film (bp-SNA) modified electrode for highly sensitive detection of carbohydrate antigen 125 (CA 125). Inexpensive and readily available indium tin oxide (ITO) electrode was used as the supporting electrode for the growth of bp-SNA. bp-SNA consists of a bilayer SNA film with different functional groups and charge properties, including negatively charged inner layer SNA (n-SNA) and positively charged outer layer SNA (p-SNA). The nanochannels of bp-SNA were used for the immobilization of ECL emitter tris(bipyridine)ruthenium(II), while the outer surface was utilized for constructing the immunorecognition interface. Due to the dual electrostatic interaction composed of electrostatic attraction from n-SNA and electrostatic repulsion from p-SNA, ECL emitter could be stably confined within bp-SNA, providing stable and high ECL signals to the modified electrode. After amino groups on the outer surface of bp-SNA were derivatized with aldehyde groups, recognition antibodies could be covalently immobilized, and an immunosensor was obtained after blocking nonspecific sites. When CA 125 binds to the antibodies on the recognition interface, the formed complex reduces the diffusion of the co-reactant tripropylamine (TPrA) to the supporting electrode, decreasing the ECL signal. Based on this mechanism, the constructed immunosensor can achieve sensitive ECL detection of CA 125. The linear detection range is from 0.01 to 100U/mL, with a detection limit of 4.7mU/mL. CA 125 detection in serum is also achieved. The construction immunosensor has advantages including simple and convenient fabrication, high stability of the immobilized emitter, and high selectivity, making it suitable for CA 125 detection.

Neoadjuvant Treatment with Changes in Chemotherapy Regimens According to Carbohydrate Antigen 19-9 Level for Resectable/Borderline Resectable Pancreatic Ductal Adenocarcinoma.

The response of carbohydrate antigen (CA) 19-9 to neoadjuvant therapy (NAT) for pancreatic ductal adenocarcinoma (PDAC) may contribute to outcomes. This study aimed to investigate the effect of changes in NAT regimens based on CA19-9 level. This single-center retrospective study included patients with resectable/borderline resectable (R/BR)-PDAC undergoing NAT from 2008 to 2022. A CA19-9 level lower than 150 IU/mL after NAT was the criterion for resection. If the level did not decrease, the chemotherapy regimen was changed to satisfy the criterion. The patient cohort was divided into group A (satisfied criterion without changing chemotherapy), group B (did not receive chemotherapy change, could not satisfy the criterion), group C (received chemotherapy change, satisfied the criterion), and group D (received chemotherapy change, could not satisfy the criterion). The study cohort included 283 patients. After first-line chemotherapy, 112 (39.6%) patients did not satisfy the criterion (groups B [n = 64], C [n = 32], and D [n = 16]). Of the 283 patients, 48 (17%) received a chemotherapy change (groups C and D). The patients in groups C and D showed significantly better overall survival (OS, 35.9 months) than the group B patients (25.7 months) (P = 0.035). The OS of the group C patients (63.8 months) was similar to the OS of the group A patients (n = 171: 56.3 months; P = 0.430). Multivariate analysis of the patients in groups B, C, and D identified chemotherapy change as an independent prognostic factor for OS and progression-free survival. Changing the chemotherapy targeting the CA19-9 level can improve the outcome of R/BR-PDAC patients with poor biologic response to first-line NAT.

Quantitative detection of miR-25 for early diagnosis, postoperative assessment and TNM staging of pancreatic cancer

Objectives: Pancreatic cancer is one of the most common malignant tumors of the digestive tract. Due to its strong concealment and rapid disease progress, it is characterized by high mortality and low cure rate. Current research focuses on screening high-risk populations, preventing the occurrence of pancreatic cancer and developing imaging technology and tumor markers for early diagnosis. This study aimed to investigate the absolute quantitative detection of microRNA-25 (miR-25) and reveal its quantitative changes in the treatment of pancreatic cancer. We compared serum miR-25 level between pancreatic cancer patients and other tumor patients, especially those with gastrointestinal cancer, to provide further evidence for early diagnosis, differential diagnosis and prognosis of pancreatic cancer. Methods: We collected serum samples from 51 pancreatic cancer patients (including 21 patients with preoperative and postoperative samples), 52 pancreatitis patients, 141 other tumor patients, and 50 healthy individuals from Huashan Hospital, Fudan University. The serum levels of miR-25, Carbohydrate Antigen 19–9 (CA19–9), Carbohydrate Antigen 125 (CA125) and Carcinoembryonic Antigen (CEA) in these populations were measured to analyze the value of miR-25 quantitative detection in the diagnosis, postoperative assessment and Tumor Node Metastasis (TNM) staging of pancreatic cancer. Results: Among the 51 pancreatic cancer patients, 50 cases (98.04 %) showed miR-25 levels above the threshold (3333 copies/μl), while all samples in normal group showed negative. The mean level of miR-25 in serum was 5707.45 ± 361.02 copies/μl. In other tumor groups, 21/141 (14.89 %) patients showed positive results and the mean miR-25 level was 847.09 ± 125.97 copies/μl. Comparing before and after operation in 21 paired samples, the level of miR-25 declined significantly after operation, with an average decline rate of 86.36 %. Conclusions: Serum miR-25 levels were significantly higher in pancreatic cancer patients compared to both normal and other tumor groups and decreased significantly after surgery. In addition, miR-25 showed higher sensitivity than common tumor markers (CA19–9, CA125, CEA) in early diagnosis of pancreatic cancer, and proved to be of significant value in evaluating the effect of surgical treatment.

Metal organic frameworks (MOFs)-based fluorescent CA125 analysis: A comparative study of the quenching effects of MIL-101, Cu-MOF, ZIF-8, UiO-66

Metal-organic frameworks (MOFs) are a class of materials with highly ordered pore structures. Due to their unique physical and chemical properties, they show great potential in the field of biosensors. Some MOFs can adsorb fluorescently labeled nucleic acid aptamers through various interaction mechanisms (such as electrostatic interactions, π-π stacking, hydrogen bonding, etc.). These interactions not only ensure the stable binding of the aptamers but also allow for their controlled release under specific conditions (such as changes in pH, temperature, or the presence of specific molecules). This mechanism provides multiple possibilities for the design of biosensors. Herein, we have systematically compared the quenching effects of widely used MOFs that can bind to aptamers, i.e., Fe-MOF (MIL-101), Cu-MOF, Zn-MOF (ZIF-8) and Zr-MOF (UiO-66). The study on the kinetics, quenching efficiency, and influencing factors such as ionic strength pH and temperature is performed. Interestingly, Cu-MOF exhibits superior quenching abilities to the other three materials in both the quenching efficiency and kinetics. Thus, a Cu-MOF based fluorescent sensor is reported to detect the ovarian cancer marker carbohydrate antigen 125 (CA125), which provides convenient detection performance (assay time about 10 min), and a detection range from 0.1 to 400 ng/mL. Moreover, it is designed in a simple mix-and-detect format and can be directly applied to clinical sample detection. This work may offer guidance for the choice of MOFs and elaborate design of biosensors.