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Objectives. Limited research on the role of membrane-bound O-acyltransferase domain–containing 2 (MBOAT2) in cancer biology exists. In particular, the underlying role of MBOAT2 and its potential mechanisms in pancreatic cancer have not yet been explored. Further study of MBOAT2 could provide new ideas about the carcinogenesis and treatment of pancreatic cancer (PC). Methods. In the current study, the potential biological and clinical significances of MBOAT2 were explored by bioinformatics analysis. Real-time quantitative polymerase chain reaction and western blot analysis were performed to determine the level of MBOAT2 in pancreatic ductal adenocarcinoma (PDAC) cell lines. MTT, colony formation, and Transwell assays and flow cytometry of cell cycle were performed to analyze PDAC cell proliferation, migration, and cycle progression. The potential relationship between MBOAT2 level and tumor immunity was analyzed using the ESTIMATE algorithm, CIBERSORT algorithm, and single-sample gene set enrichment analysis. Results. The level of MBOAT2 was remarkably upregulated in most tumors, especially pancreatic tumors, and was positively correlated with a greater rate of tumor recurrence, higher histologic grade, and worse overall survival. MBOAT2 overexpression was also closely correlated with the mutation status and expression level of driver genes, especially KRAS. Meanwhile, functional enrichment analysis demonstrated that MBOAT2 might be involved in cell–cell communication; cell cycling; the Ras signaling pathway; and immune-related biological functions such as the leukocyte activation involved in T-cell–receptor signaling pathway, the inflammatory response, and antigen processing and presentation. Furthermore, in vitro experiments demonstrated that MBOAT2 overexpression accelerated PC cell proliferation and migration. MBOAT2 overexpression also enhanced CDK2 and CCNA2 expression, leading to cell cycle progression from the G1 phase to the G2 phase. Lastly, MBOAT2 overexpression reduced the infiltration level of CD8+ T-cells, plasmacytoid dendritic cells, and activated dendritic cells but triggered a high type-2 T helper/type-1 T helper cell ration (Th2/Th1 ration) in PC. Conclusion. Our findings suggest that MBOAT2 is a potential protooncogene in PDAC that predicts a poor prognosis and is related to KRAS activation and inferior infiltration of CD8+ T-cells in PC. [ABSTRACT FROM AUTHOR]

Background. KRAS was reported to affect some metabolic genes and promote metabolic reprogramming in solid tumors. However, there was no comprehensive analysis to explore KRAS-associated metabolic signature or risk model for pancreatic cancer (PC). Methods. In the current study, multiple bioinformatics analyses were used to identify differentially expressed metabolic genes based on KRAS mutation status in PC. Then, we developed and validated a prognostic risk model based on the selected KRAS-associated metabolic genes. Besides, we explored the association between the risk model and the metabolic characteristics as well as gemcitabine-associated chemoresistance in PC. Results. 6 KRAS-associated metabolic genes (i.e., CYP2S1, GPX3, FTCD, ENPP2, UGT1A10, and XDH) were selected and enrolled to establish a prognostic risk model. The prognostic model had a high C-index of 0.733 for overall survival (OS) in TCGA pancreatic cancer database. The area under the curve (AUC) values of 1- and 3-year survival were both greater than 0.70. Then, the risk model was validated in two GEO datasets and also presented a satisfactory discrimination and calibration performance. Further, we found that the expression of some KRAS-driven glycolysis-associated genes (PKM, GLUT1, HK2, and LDHA) and gemcitabine-associated chemoresistance genes (i.e., CDA and RMM2) was significantly upregulated in high-risk PC patients evaluated by the risk model. Conclusions. We constructed a risk model based on 6 KRAS-associated metabolic genes, which predicted patients' survival with high accuracy and reflected tumor metabolic characteristics and gemcitabine-associated chemoresistance in PC. [ABSTRACT FROM AUTHOR]

Family with sequence similarity 83 (FAM83) members were shown recently to have oncogenic effect in a variety of cancer types, but the biological roles and prognostic value of FAM83 family in pancreatic ductal adenocarcinoma remain unknown. In the current study, the clinical significance and molecular function of the FAM83 family were assessed by multiple bioinformatics analysis. Besides, potential associations between differentially expressed genes (DEGs) of FAM83 family and antitumor immunity were evaluated using TIMER and TISIDB analyses. As the results show, FAM83A, FAM83D, FAM83E, and FAM83H were significantly upregulated in PDAC and were identified as DEGs. Higher expression of FAM83A, FAM83B, FAM83D, FAM83E, and FAM83H were associated with advanced tumor stage or worse patient prognosis. Importantly, the overexpression of DEGs was found to be significantly correlated with activated KRAS and loss of SMAD4, which are important drivers for PDAC. Further, FAM83A, FAM83D, and FAM83H were associated with CD8+ T cell, Gamma Delta T cell, and CD4+ T cell infiltration in PDAC and FAM83H was found closely correlated with some immunomodulators including immunoinhibitors, immunostimulators, and MHC molecules. In conclusion, FAM83A, FAM83D, FAM83E, and FAM83H have significant prognostic value in PDAC and they may play important roles in regulating tumor progression and the immune cell infiltration. [ABSTRACT FROM AUTHOR]

Background. Gallbladder cancer (GBC), which accounts for more than 80% of biliary tract malignancies, has a poor prognosis with an overall 5-year survival less than 10%. The study aimed to identify risk factors and develop a predictive model for GBC following surgical resection. Methods. 98 GBC patients who underwent surgical resection from Guangdong Provincial People's Hospital were enrolled in the study. Cox-regression analysis was performed to identify significant prognostic factors. A nomogram was constructed and Harrell's concordance index, calibration plot, and decision cure analysis were used to evaluate the discrimination and calibration of the nomogram. Results. Liver resection, tumor size, perineural invasion, surgical margin, and liver invasion were identified as independent risk factors for overall survival (OS) in GBC patients who underwent surgical resection. Based on the selected risk factors, a novel nomogram was constructed. The C-index of the nomogram was 0.777, which was higher than the American Joint Committee on Cancer (AJCC) staging system (0.724) and Nevin staging system (0.659). Decision cure analysis revealed that the nomogram had a better net benefit and the calibration curves for the 1-, 3-, and 5-year survival probabilities were also well matched with the actual survival rates. Lastly, high-risk GBC were stratified based on the scores of the nomogram and we found high-risk GBC were associated with both worse OS and disease-free survival (DFS). Conclusion. We developed a nomogram showing a better predictive capacity for patients' survival of resected GBC than the AJCC staging systems. The established model may help to stratify high-risk GBC and facilitate decision-making in the clinic. [ABSTRACT FROM AUTHOR]