Identification of MBOAT2 as an Unfavorable Biomarker Correlated with KRAS Activation and Reduced CD8(+) T-Cell Infiltration in Pancreatic Cancer

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.