Carbohydrate Antigen Research Articles

Association of CA-125 with markers of congestion, and effect of empagliflozin on CA-125 in patients with type 2 diabetes, or prediabetes, and heart failure with reduced ejection fraction (SUGAR-DM-HF)

Abstract Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of heart failure hospitalisation and cardiovascular death in patients with heart failure and reduced ejection fraction (HFrEF). However, their effects on carbohydrate antigen 125 (CA-125) are uncertain. CA-125 has a potential role in HFrEF in the assessment of congestion, guiding decongestive therapies, and predicting outcome. Purpose This exploratory biomarker substudy of the SUGAR-DM-HF trial investigated the relationship of CA-125 levels with markers of congestion, and the effect of the SGLT2 inhibitor empagliflozin on serum CA-125 levels. Methods We conducted a multicentre, randomised, double-blind, placebo-controlled trial investigating the effects of empagliflozin in patients with New York Heart Association functional class II-IV, left ventricular ejection fraction (LVEF) ≤40%, and type 2 diabetes or prediabetes.[1] Patients were randomly assigned 1:1 to empagliflozin 10mg daily or placebo. Blood biomarker samples were collected at baseline, weeks 12 and 36. Other measures of congestion assessed included cardiovascular magnetic resonance (CMR), kidney magnetic resonance imaging (MRI), transthoracic echocardiography (TTE), lung ultrasound (LUS), and bioelectrical impedance analysis (BIA). Results Among 105 patients [mean age 68.7 (SD, 11.1) years, 77 (73.3%) male, 82 (78.1%) diabetes and 23 (21.9%) prediabetes, mean LVEF 32.5% (9.8%)], median [IQR] CA-125 was 11.2 [8.9-17.6] U/mL. At baseline, those with higher CA-125 had a longer duration of diabetes, higher heart rate, lower LVEF, higher N-terminal pro-B-type natriuretic peptide (NT-proBNP), were more likely to have a pleural effusion and be on a loop diuretic, but serum creatinine was similar. At baseline, CA-125 levels weakly correlated with NT-proBNP, the presence of a pleural effusion, number of B-lines, inferior vena cava (IVC) diameter, tricuspid regurgitation velocity, E/e’ average, apparent extracellular volume (aECV) of the right whole kidney,[2] and total body water (FIGURE 1). CA-125 levels were not significantly different between groups at week 12 or 36 (FIGURE 2). The beneficial effect of empagliflozin on reducing left ventricular end-systolic volume index (LVESVi) was not modified by baseline CA-125 (p interaction = 0.93). Change in CA-125 was not associated with change in the co-primary outcomes (LVESVi and left ventricular global longitudinal strain) at week 36, nor with change in NT-proBNP or change in body weight at week 12 or 36. Conclusion Among patients with HFrEF, CA-125 levels were not strongly associated with markers of congestion assessed with CMR, kidney MRI, TTE, LUS and BIA. CA-125 levels were not different between groups at week 12 or 36, although this trial was not powered for this outcome.Correlation heatmap (Spearman’s rho).Change in CA-125 levels.

Sequential high-intensity focused ultrasound treatment combined with chemotherapy for inoperable pancreatic cancer: a retrospective analysis for prognostic factors and survival outcomes

Objective To evaluate the effect of HIFU (High-Intensity Focused Ultrasound) therapy on the survival and prognosis of patients with inoperable pancreatic cancer, and the clinical application of serological prognostic indicators. Methods We retrospectively analyzed the clinicopathological features, laboratory tests and follow-ups of 192 patients. Among the patients, 57 were treated with HIFU prior to chemotherapy (HIFU-priority), and 135 patients received chemotherapy followed by HIFU (HIFU-second). Univariate and multivariate Cox regression analysis was used to determine the prognostic value of tumor inflammation-related serological markers. A nomogram model was established based on the identified prognostic factors. Results Univariate analysis showed that receiving the treatment regimen in HIFU-priority was a significant protective factor for overall survival (OS, p < 0.001). Tumor stage, high C-reactive protein (CRP), high gamma-glutamyl transferase(γGT) high carbohydrate antigen 125 (CA125), high neutrophil-to-lymphocyte ratio (NLR), high lymphocyte-to-monocyte ratio (LMR) and liver metastasis were significant risk factors for poor prognosis (p < 0.05). CRP combined with normal tumor marker CA125 (CRP + CA125) was associated with longer OS (p = 0.005). Multivariate analysis shows that HIFU-priority is a protective factor for OS (Hazard Ratio, HR: 0.38; 95% confidence interval(CI): 0.25-0.57), tumor stage (HR: 1.61; 95% CI: 1.12-2.31), CRP + CA125 (HR: 1.46; 95% CI: 1.02-2.08) and γGT (HR: 1.44; 95% CI: 1.04-1.98) are risk factors for OS and serve as independent prognostic factors in the nomogram. Conclusion Early application of HIFU treatment improves the OS of patients with inoperable pancreatic cancer. CRP + CA125 and γGT are independent prognostic factors.

Pancreatic index: A prognostic factor of upfront surgery for body or tail pancreatic ductal adenocarcinoma with vascular involvement-A retrospective study.

The pancreatic index (PI) is a useful preoperative imaging predictor for pancreatic ductal adenocarcinoma (PDAC). In this retrospective study, we determined the predictive effect of PI to distinguish patients of pancreatic body/tail cancer (PBTC) with vascular involvement who can benefit from upfront surgery. All patients who received distal pancreatectomy for PDAC from 2016 to 2020 at the Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine were considered for the study. A total of 429 patients with PBTC were assessed in relation to the value of PI. Fifty-five patients were eventually included and divided into low PI group and 29 patients in the normal PI group. The median overall survival (mOS) was significantly shorter in the low PI group (13.1 vs. 30.0 months, p = 0.002) in this study, and PI ≥ 0.78 (OR = 0.552, 95% CI: 0.301-0.904, p = 0.020) was an independent influencing factor confirmed by multivariate analysis. Subgroup analysis showed that PI was an independent prognostic factor for LA-PBTC (OR = 0.272, 95% CI: 0.077-0.969, p = 0.045). As for BR PBTC, PI (OR = 0.519, 95% CI: 0.285-0.947, p = 0.033) combined with carbohydrate antigen 125 (CA125) (OR = 2.806, 95% CI: 1.206-6.526, p = 0.017) and chemotherapy (OR = 0.327, 95% CI: 0.140-0.763, p = 0.010) were independent factors. This study suggests that the PI can be used as a predictive factor to optimize the surgical indication for PBTC with vascular involvement. Preoperative patients with normal PI and CA125 can achieve a long-term prognosis comparable to that of resectable PBTC patients.

Elucidation of the Binding Orientation in α2,3- and α2,6-Linked Neu5Ac-Gal Epitopes toward a Hydrophilic Molecularly Imprinted Monolith.

N-Acetylneuraminic acid and its α2,3/α2,6-glycosidic linkages with galactose (Neu5Ac-Gal) are major carbohydrate antigen epitopes expressed in various pathological processes, such as cancer, influenza, and SARS-CoV-2. We here report a strategy for the synthesis and binding investigation of molecularly imprinted polymers (MIPs) toward α2,3 and α2,6 conformations of Neu5Ac-Gal antigens. Hydrophilic imprinted monoliths were synthesized from melamine monomer in the presence of four different templates, namely, N-acetylneuraminic acid (Neu5Ac), N-acetylneuraminic acid methyl ester (Neu5Ac-M), 3'-sialyllactose (3SL), and 6'-sialyllactose (6SL), in a tertiary solvent mixture at temperatures varying from -20 to +80 °C. The MIPs prepared at cryotemperatures showed a preferential affinity for the α2,6 linkage sequence of 6SL, with an imprinting factor of 2.21, whereas the α2,3 linkage sequence of 3SL resulted in nonspecific binding to the polymer scaffold. The preferable affinity for the α2,6 conformation of Neu5Ac-Gal was evident also when challenged by a mixture of other mono- and disaccharides in an aqueous test mixture. The use of saturation transfer difference nuclear magnetic resonance (STD-NMR) on suspensions of crushed monoliths allowed for directional interactions between the α2,3/α2,6 linkage sequences on their corresponding MIPs to be revealed. The Neu5Ac epitope, containing acetyl and polyalcohol moieties, was the major contributor to the sequence recognition for Neu5Ac(α2,6)Gal(β1,4)Glc, whereas contributions from the Gal and Glc segments were substantially lower.

Feasibility of 125I brachytherapy combined with arterial infusion chemotherapy in patients with advanced pancreatic cancer.

To evaluation the feasibility of Iodine-125 (¹²5I) brachytherapy combined with arterial infusion chemotherapy in patients with advanced pancreatic cancer. A total of 72 cases with Stage III and IV were retrospectively reviewed. 23 cases receiving 125I brachytherapy were classified as Group A. 27 cases receiving arterial infusion chemotherapy (gemcitabine + cisplatin, GP) were classified as Group B and 22 cases receiving 125I brachytherapy combined with arterial infusion chemotherapy (GP) were classified as Group C. The evaluated indications were local control rate, survival rate, carbohydrate antigen 19-9, pain relief, and Karnofsky physical scores. Analysis of Variancep, Pearson chi-square test and Kaplan-Meier curves were used for analysis. The local control rate of group A and group C was significantly higher than group B (P < .001). Pearson chi-square test showed statistical difference of the 3 groups (χ2 = 12.969, P = .044). The median survival of group A,B and C was 9 months, 6 months and 13 months, respectively. The survival time of group C was significantly higher than group B (χ2 = 5.403, P = .020). The Log rank test showed statistical difference in the survival curve of the 3 groups (χ2 = 6.501, P = .039). The difference of carbohydrate antigen 19-9 decline percentage between group B and C group was statistically significant (χ2 = 5.959, P = .015). Patients in group A and group C relieved form pain after treatment with statistically significant (P < .001). Pain relief was much more effective in patients who received 125I brachytherapy. Karnofsky physical scores after treatment were statistically higher than those before treatment in each group (P < .001). 125I brachytherapy maybe one of the effective, safe and feasible alternative treatment of advanced pancreatic cancer. ¹²5I brachytherapy combined with arterial infusion chemotherapy was effective in the treatment of advanced pancreatic cancer.

Prognostic Value of Serum Neutrophil to Lymphocyte Ratio and SUVmax in Stage I and II Colon Cancer.

This study aimed to evaluate the correlation between maximal standardized uptake value (SUVmax) of primary colon cancer and serum neutrophil-to-lymphocyte ratio (NLR), and to assess the prognostic value of SUVmax and serum NLR in stage I and II colon cancer patients. In this retrospective study a total of 128 patients with pathologically confirmed stage I and II colon cancer diagnosed between January 2014 and December 2017 were included. All patients underwent F-18 Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and differential white blood cell (WBC) counts before surgery. The correlations between SUVmax and NLR were assessed. The prognostic value of SUVmax and NLR for predicting recurrence-free survival (RFS) was investigated. The mean NLR was 2.2 ± 1.2, and the mean SUVmax of primary tumor was 15.2 ± 7.9. There was significant correlation between NLR and SUVmax (rho=0.2, p=0.02). Mean follow-up period was 59.8 ± 19.2 months and 12 patients experienced a recurrence. In univariable analysis, NLR (p=0.0084, HR=5.0223, 95% CI=1.5117-16.6853), C-reactive protein (CRP) (p=0.021, HR=4.1115, 95% CI=1.2380-13.6551), carbohydrate antigen 19-9 (CA19-9) (p=0.0134, HR=4.2683, 95% CI=1.3519-13.4766), and Kirsten ras sarcoma viral oncogene (KRAS) mutation (p=0.0338, HR=3.4703, 95% CI=1.0998-10.9499) were significant prognostic factors for the recurrence. In multivariable analysis, NLR (p=0.0256, HR=4.1155, 95% CI=1.1887-14.2490) and CA19-9 (p=0.0257, HR=4.139, 95% CI=1.1880-14.4200) were independent prognostic factors for the recurrence. Significant correlation was observed between SUVmax of primary colon cancer and serum NLR. Furthermore, in the multivariable analysis conducted on early colon cancer cases, NLR and CA19-9 were found to be independently associated with RFS. This suggested that NLR could be used as a supplementary tool for identifying patients at high risk of recurrence in early colon cancer. However, SUVmax was not associated with prognosis, suggesting that it cannot be used for predicting prognosis in early colon cancer.

Identifying tumor markers-stratified subtypes (CA-125/CA19-9/carcinoembryonic antigen) in cervical adenocarcinoma.

There is a lack of research evaluating the effect of tumor markers for prognosis in cervical adenocarcinoma. We aimed to develop and validate a preoperative tumor-marker-based model including clinicopathological factors to clarify the prognostic value of endocervical adenocarcinoma. A total of 572 patients with cervical adenocarcinoma who were staged at the International Federation of Gynecology and Obstetrics (FIGO) IA-IIA were reviewed retrospectively. Preoperative serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA)-125 and CA19-9 levels were measured. The survival and recurrence patterns were analyzed according to the tumor-marker-related stratification. The predictive values of biomarkers and clinical variables were assessed with Cox regression and competing risk models. Patients with elevated preoperative tumor markers had evidently poor overall survival and recurrence-free survival. The triple-elevated tumor marker (TETM) subgroup had the worst overall survival and progression-free survival than the triple-negative tumor marker (TNTM) subgroup and the single-elevated tumor marker (SETM) subgroup. The most important predictors for overall survival were elevated tumor markers, FIGO-stage, tumor differentiation, lymphovascular space invasion (LVSI) and lymph nodes metastasis. The most important predictors for recurrence-free survival were elevated tumor markers, FIGO-stage, tumor differentiation, LVSI and deep stromal invasion. Stratified analysis showed that elevated CA-125 and CA19-9 were significantly associated with postoperative distant metastasis. A decision curve analysis confirmed that a combination of tumor markers as predictors significantly outperformed the other common predictors used (FIGO-stage, intermediate and high-risk factors, tumor differentiation, lymph nodes). Elevated preoperative serum CEA, CA-125, and CA19-9 levels exhibited poor overall survival and recurrence-free survival in cervical adenocarcinoma patients. Combined preoperative serum CA-125 and CA19-9 independently predicted distant metastasis in patients with endocervical adenocarcinoma.

Does Chinese herbal medicine (CHM) reduce colorectal adenoma (CRA) recurrence: protocol of a registry-based, cohort study and a qualitative interview

IntroductionColorectal adenoma (CRA) is a precancerous lesion for colorectal cancer. Endoscopic resection is the first-line treatment for CRA. However, CRA recurrence rate is high. This proposed study aims to determine...

Carbohydrate antigen 125 in congestive heart failure: ready for clinical application?

Congestion is the permanent mechanism driving disease progression in patients with acute heart failure (AHF) and also is an important treatment target. However, distinguishing between the two different phenotypes (intravascular congestion and tissue congestion) for personalized treatment remains challenging. Historically, carbohydrate antigen 125 (CA125) has been a frequently used biomarker for the screening, diagnosis, and prognosis of ovarian cancer. Interestingly, CA125 is highly sensitive to tissue congestion and shows potential for clinical monitoring and optimal treatment of congestive heart failure (HF). Furthermore, in terms of right heart function parameters, CA125 levels are more advantageous than other biomarkers of HF. CA125 is expected to become a new biological alternative marker for congestive HF and thereby is expected be widely used in clinical practice.

ASO Author Reflections: Postoperative Carbohydrate Antigen 19-9 Levels Become a Reliable Biomarker for Establishing Intensity-Stratified Adjuvant Treatments in Pancreatic Ductal Adenocarcinoma.

ASO Author Reflections: Postoperative Carbohydrate Antigen 19-9 Levels Become a Reliable Biomarker for Establishing Intensity-Stratified Adjuvant Treatments in Pancreatic Ductal Adenocarcinoma.

A Case of Complete Remission from Pancreatic Cancer Following Palliative Chemotherapy

The prognosis for pancreatic cancer is still poor with a 5-year survival rate around 10%. We report a case of complete remission after palliative chemotherapy for pancreatic cancer in a 61-year-old-female. She presented with indigestion and weight loss. A computed tomography scan revealed a 1.8 cm mass in the pancreatic head. Carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) levels were elevated. The patient underwent endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) and the pathologic examination showed adenocarcinoma. Positron emission tomography (PET) and magnetic resonance imaging (MRI) of the pancreas showed a metastatic nodule in the S6 segment of the liver and a metastatic portocaval lymph node. The final diagnosis was stage IV pancreatic cancer. The patient received 24 cycles of palliative FOLFIRINOX regimen. Response evaluation demonstrated disappearance of all the lesions. She underwent pyloruspreserving pancreatoduodenectomy (PPPD). The pathologic examination of the surgical specimen showed complete remission of the pancreatic cancer. The patient is currently undergoing adjuvant chemotherapy.

Nomogram based on preoperative clinical and MRI features to estimate the microvascular invasion status and the prognosis of solitary intrahepatic mass-forming cholangiocarcinoma.

To develop a nomogram based on preoperative clinical and magnetic resonance imaging (MRI) features for the microvascular invasion (MVI) status in solitary intrahepatic mass-forming cholangiocarcinoma (sIMCC) and to evaluate whether it could predict recurrence-free survival (RFS). We included 115 cases who experienced MRI examinations for sIMCC with R0 resection. The preoperative clinical and MRI features were extracted. Independent predictors related to MVI+ were evaluated by stepwise multivariate logistic regression, and a nomogram was constructed. A receiver operating characteristic (ROC) curve was used to assess the predictive ability. All patients were classified into high- and low-risk groups of MVI. Then, the correlations of the nomogram with RFS in patents with sIMCC were analyzed by Kaplan-Meier method. The occurrence rate of MVI+ was 38.3% (44/115). The preoperative independent predictors of MVI+ were carbohydrate antigen 19-9 >37U/ml, tumor size >5cm, and an ill-defined tumor boundary. Integrating these predictors, the nomogram exerted a favorable diagnostic performance with areas under the ROC curve of 0.767 (95% confidence interval [CI] 0.654-0.881) in the development cohort, and 0.760 (95% CI 0.591-0.929) in the validation cohort. In the RFS analysis, significant differences were observed between the high- and low-risk MVI groups (6-month RFS rates: 64.5% vs. 78.8% and 46.7% vs. 82.4% in the development and validation cohorts, respectively) (P<0.05). A nomogram based on clinical and MRI features is a potential biomarker of MVI and may be a potent method to classify the risk of recurrence in patients with sIMCC.

Peak Risk of Recurrence Occurs during the First Two Years after a Pancreatectomy in Patients Receiving Neoadjuvant FOLFIRINOX

No codified/systematic surveillance program exists for borderline/locally advanced pancreatic ductal carcinoma treated with neoadjuvant FOLFIRINOX and a secondary resection. This study aimed to determine the trend of recurrence in patients who were managed using such a treatment strategy. From 2010, 101 patients received FOLFIRINOX and underwent a pancreatectomy, in a minimum follow-up of 5 years. Seventy-one patients (70%, R group) were diagnosed with recurrence after a median follow-up of 11 months postsurgery. In the multivariable analysis, patients in the R-group had a higher rate of weight loss (p = 0.018), higher carbohydrate antigen (CA 19-9) serum levels at diagnosis (p = 0.012), T3/T4 stage (p = 0.017), and positive lymph nodes (p &lt; 0.01) compared to patients who did not experience recurrence. The risk of recurrence in patients with T1/T2 N0 R0 was the lowest (19%), and all recurrences occurred during the first two postoperative years. The peak risk of recurrence for the entire population was observed during the first two postoperative years. The probability of survival decreased until the second year and rebounded to 100% permanently, after the ninth postoperative year. Close monitoring is needed at reduced intervals during the first 2 years following a pancreatectomy and should be extended to later than 5 years for those with unfavorable pathological results.

Dynamic monitoring of serum CEA and CA19-9 predicts the prognosis of postoperative stage II colon cancer

BackgroundWe sought to investigate the prognostic significance of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) dynamics for stage II colon cancer patients undergoing radical resection. MethodsThis study retrospectively analyzed 1517 stage II colon cancer patients admitted to the Harbin Medical University Cancer Hospital from January 2011 to December 2016. To observe the relationship between tumor markers dynamic monitoring and survival, we calculated cut-off values for ΔCEA and ΔCA19-9. Group according to the cut-off values and compare the differences in survival between subgroups. ResultsPreoperative CA199 (HR = 3.122), postoperative CEA (HR = 2.941) and histological type (HR = 2.855) were independent prognostic factors in multivariate Cox proportional hazards models. The 5-year overall survival (OS) in the patients with normal preoperative CEA and CA19-9 was significantly better than the patients with elevated preoperative CEA or CA19-9 and the patients with elevated preoperative CEA and CA19-9 (92.6 % vs. 87.6 % vs. 81.0 %, P < 0.05). 469 patients with normal pre- and post-operative CEA had the highest 5-year OS (93.5 %, P < 0.05). Among the 177 patients with elevated pre- and post-operative CEA, the 5-year OS rate was only 81.8 % (P < 0.05). The cut-off values for Δ CEA and Δ CA19-9 in stage II colon cancer patients with elevated preoperative tumor markers were 2.625 ng/ml and 7.835 U/ml, respectively. The Kaplan-Meier curves showed that Δ CEA≥2.625 ng/ml and Δ CA19-9≥7.835 U/mL were associated with better outcome (87.8 % vs. 79.6 %, P < 0.05; 85.8 % vs. 79.1 %, P > 0.05). At the same time, we found that adjuvant chemotherapy significantly improved 5-year OS in patients with elevated preoperative CEA or CA19-9 (91.0 % vs. 80.9 % and 89.6 % vs. 80.2 %, P < 0.05). ConclusionsPersistent postoperative elevation of CEA/CA19-9 is associated with a poor prognosis. CEA and CA19–9 may be high-risk factors for postoperative adjuvant therapy in stage II colon cancer patients. For stage II colon cancer patients with elevated preoperative CEA, patients with Δ CEA<2.625 ng/ml have poor survival and can improve prognosis by receiving adjuvant therapy.

FTO, PIK3CB serve as potential markers to complement CEA and CA15-3 for the diagnosis of breast cancer.

The diagnostic efficacy of carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15-3) is limited in breast cancer (BC), highlighting the necessity of exploring novel biomarkers to improve for BC diagnosis. Therefore, we assessed the diagnostic value of fat mass and obesity-associated protein (FTO), phosphatidylinositol-4,5-biphosphate 3-kinase catalytic subunit β (PIK3CB) as a potential complementary biomarker to CEA and CA153 in breast cancer by measuring serum FTO,PIK3CB levels. FTO, PIK3CB, CEA and CA15-3 levels were measured in 112 BC patients and 64 healthy controls using enzyme-linked immunosorbent assay or electrochemiluminescence immunoassay. Spearman's rank correlation analysis was conducted to assess the correlation between the levels of the 2 markers. The relationships between FTO, PIK3CB, CEA, CA15-3 and clinical characteristics were evaluated. Receiver operating characteristic curve (ROC) analysis was performed to assess the diagnostic value of FTO, PIK3CB, CEA and CA15-3 of BC. Serum FTO, PIK3CB, CEA and CA15-3 levels were significantly increased in BC. There was no correlation between FTO, PIK3CB and CEA, CA15-3. FTO and PIK3CB demonstrated significant diagnostic performance for breast cancer, with FTO achieving a specificity of 90.63%. The diagnostic performance of 2-four biomarker combinations was significantly superior to individual CEA or CA153, with a combined panel of 4 biomarkers yielding an area under the curve (AUC) of 0.918, sensitivity of 81.25% and specificity of 85.94%. In early-stage breast cancer (I + II), the combination of FTO, PIK3CB, CEA and CA153 yielded an AUC of 0.895, sensitivity of 77.22% and specificity of 85.71%. FTO and PIK3CB can be served as potential biomarkers to complement CEA and CA15-3 for BC diagnosis. Combining FTO, PIK3CB, CEA and CA15-3 improves the diagnostic efficiency of breast cancer.

Dual-energy CT improves differentiation of non-hypervascular pancreatic neuroendocrine neoplasms from CA 19-9-negative pancreatic ductal adenocarcinomas.

To evaluate the utility of dual-energy CT (DECT) in differentiating non-hypervascular pancreatic neuroendocrine neoplasms (PNENs) from pancreatic ductal adenocarcinomas (PDACs) with negative carbohydrate antigen 19-9 (CA 19-9). This retrospective study included 26 and 39 patients with pathologically confirmed non-hypervascular PNENs and CA 19-9-negative PDACs, respectively, who underwent contrast-enhanced DECT before treatment between June 2019 and December 2021. The clinical, conventional CT qualitative, conventional CT quantitative, and DECT quantitative parameters of the two groups were compared using univariate analysis and selected by least absolute shrinkage and selection operator regression (LASSO) analysis. Multivariate logistic regression analyses were performed to build qualitative, conventional CT quantitative, DECT quantitative, and comprehensive models. The areas under the receiver operating characteristic curve (AUCs) of the models were compared using DeLong's test. The AUCs of the DECT quantitative (based on normalized iodine concentrations [nICs] in the arterial and portal venous phases: 0.918; 95% confidence interval [CI] 0.852-0.985) and comprehensive (based on tumour location and nICs in the arterial and portal venous phases: 0.966; 95% CI 0.889-0.995) models were higher than those of the qualitative (based on tumour location: 0.782; 95% CI 0.665-0.899) and conventional CT quantitative (based on normalized conventional CT attenuation in the arterial phase: 0.665; 95% CI 0.533-0.797; all P < 0.05) models. The DECT quantitative and comprehensive models had comparable performances (P = 0.076). Higher nICs in the arterial and portal venous phases were associated with higher blood supply improving the identification of non-hypervascular PNENs.

High expression of RAB7A is associated with poor prognosis of gastric cancer by promoting tumor invasion

To explore the expression level of Ras-related protein 7A (RAB7A) in gastric cancer and its prognostic implications. Based on data from public databases and a cohort of 104 patients undergoing radical gastrectomy for gastric cancer in our hospital, we analyzed RAB7A expression level in gastric cancer and adjacent tissues and its association with clinicopathological parameters and prognosis of the patients. Bioinformatic analysis was performed to predict the pathways of RAB7A to affect gastric cancer invasion. In gastric cancer MGC803 cells with lentivirus-mediated interference or overexpression of RAB7A, the changes in extracellular matrix (ECM) degradation and cell migration and invasion were analyzed using immunoblotting, wound healing assay and Transwell experiments. The data from public cancer databases and clinical samples showed a significantly higher expression of RAB7A in gastric cancer tissues than in normal or adjacent tissues (P<0.01) with a close correlation with a poorer patient survival (P<0.01) and a positive correlation with serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels (P<0.001). Univariate and multivariate Cox regression analyses suggested that a high RAB7A expression was an independent risk factor affecting the 5-year survival rate of gastric cancer patients (HR: 2.882; 95% CI: 1.459-5.693). ROC curve analysis showed that at the cut-off value of 2.625, RAB7A expression level had a sensitivity of 84.62% and a specificity of 71.15% for predicting postoperative 5-year mortality of the patients. Bioinformatic analysis suggested that RAB7A was involved in ECM degradation and activation of PI3K/AKT signaling in gastric cancer. MGC803 cells with RAB7A overexpression showed activation of the PI3K/AKT signaling pathway (P<0.01) with enhanced expressions of MMP-2 and MMP-9 (P<0.01) and cell migration and invasion capacities (P<0.01). RAB7A is highly expressed in gastric cancer tissues and affects the patients' prognosis possibly by activating the PI3K/AKT signaling pathway and enhancing ECM degradation to promote tumor invasion.

Postoperative Carbohydrate Antigen 19-9 Level as a Good Indicator of Ineffective Response to the Currently Recommended S-1 Adjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma: A Single-Center, Retrospective Study.

The intensity of adjuvant treatment for pancreatic ductal adenocarcinomas (PDACs) has not been stratified according to the risk after resection. This study was designed to identify patients with PDACs in whom the current S-1 adjuvant treatment is ineffective. This single-center, retrospective study included patients who underwent pancreatectomy for PDACs from 2009 to 2020 at Sendai Open Hospital and were receiving S-1 adjuvant treatment. The independent risk factors for recurrence and survival were determined by using a Cox proportional hazards regression model. The effects of S-1 adjuvant treatment and detailed patterns of recurrence were evaluated in patients with high-risk factors. Overall, 118 patients with PDAC received S-1 adjuvant treatment. Postoperative nonnormalized carbohydrate antigen (CA19-9) was a predictive risk factor for recurrence (p < 0.010; hazard ratio [HR], 3.87; 95% confidence interval [CI], 2.26-6.62) and survival (p = 0.008; HR, 2.25; 95% CI, 1.24-4.11) after S-1 adjuvant treatment. In 24 patients with nonnormalized postoperative CA19-9, S-1 monotherapy was ineffective in preventing recurrence, even during the treatment period, compared with that noted in patients who did not receive adjuvant treatment. The recurrence rate during adjuvant treatment was 41.7%; in all cases, recurrence was caused by distant metastasis. The total recurrence rate was up to 95.8%, and distant recurrence was especially frequent. The current S-1 adjuvant treatment regimen is ineffective for patients with postoperative nonnormalized CA19-9. The postoperative CA19-9 level may be a good indicator for further aggressive treatment. This study may lead to further discussions on intensity stratification of adjuvant treatments for PDAC.

MUC16 C terminal fragment activates YAP1 through Src signaling to promote gallbladder cancer growth

AbstractThe Hippo pathway is crucial to organ size control and its dysregulation contributes to tumorigenesis. The aberrant activation of YAP1 was identified in gallbladder cancer (GBC). However, the underlying mechanism and role in GBC remains unclear. The C terminal fragment of Mucin16, also known as carbohydrate antigen 125 (CA125) encoded product, MUC16c, plays extensive roles in tumor initiation and development. Our study showed that MUC16c binding with 14‐3‐3ε disrupted the interaction of 14‐3‐3ε and phosphorylated yes‐associated protein 1 (YAP1), which led to the activation of YAP1 in GBC. Furthermore, MUC16c decreased the phosphorylation of YAP1 at serine 397 (ser397) by inhibiting LATS1, which upregulated YAP1 protein stability. Interestingly, there was a potential Src kinase site in the MUC16c fragment. The MUC16c_del15Y polypeptides with the deletion of the Src kinase site promoted the interaction of YAP1 with 14‐3‐3ε and downregulated the YAP1 protein levels. Consistently, SU6656, a Src kinase inhibitor also blocked the activation of YAP1 by MUC16c. The MUC16c_del15Y polypeptides decreased GBC cell proliferation in vitro and the growth of xenograft tumors in vivo. Our study revealed the underlying mechanism of the activation of MUC16c on YAP1 mediated by Src signaling and the antitumor effect of MUC16c_del15Y, providing a potential target for GBC therapy.

Combination of carbohydrate antigen 19-9 level and tumor size after neoadjuvant chemoradiation therapy may predict early recurrence of resectable pancreatic ductal adenocarcinoma

BackgroundAlthough the overall survival rate of patients with resectable pancreatic cancer has gradually improved, some patients relapse early and have a poor prognosis. This study aimed to identify the preoperative risk factors for early recurrence after neoadjuvant chemoradiotherapy in patients with resectable pancreatic cancer. MethodsThis study analyzed patients who underwent pancreatectomy after receiving neoadjuvant chemoradiotherapy for resectable pancreatic cancer between January 2009 and June 2021 and excluded those with borderline resectable and unresectable pancreatic cancers. Early recurrence was defined as recurrence within 6 months after surgery. ResultsThis study included 203 patients, of whom 22 experienced early recurrence. The median survival time of patients with early recurrence was 18.3 months, which was significantly worse than that of patients with late recurrence (44.0 months, p < 0.001) or no recurrence (not reached, p < 0.001). Logistic regression analysis revealed that a carbohydrate antigen 19-9 level of >100 units/mL and a T status of ≥T2 after neoadjuvant chemoradiotherapy were independent predictive risk factors for early recurrence. The median recurrence-free survival time of patients with two risk factors was 9.7 months and significantly worse than that of those with either risk factors (20.5 months, p = 0.024) and those with no risk factor (26.2 months, p < 0.001). ConclusionsA combination of a high-level carbohydrate antigen 19–9 and a T status of ≥T2 after neoadjuvant chemoradiotherapy are predictors of early recurrence and may be helpful for selecting patients who require a stronger preoperative treatment.