Background: Pancreatic adenocarcinoma (PAAD) is one of the common Malignant tumours of the digestive tract worldwide. Chromobox (CBX) family proteins are important components of epigenetic regulation complexes and play key roles in various biological processes. However, the expression level, biological function and immune infiltration of different E2Fs in PAAD and prognostic roles of various CBX family members in Pancreatic adenocarcinoma (PAAD) remain unclear.
Methods: In this study, we used multiple bioinformatics tools including Oncomine, GEPIA, Kaplan-Meier plotter, cBioPortal, GeneMANIA, TIMER and R Tools to analyze expression levels, prognostic value, genetic alteration, immune cell infiltration and risk factors of CBXs in Pancreatic adenocarcinoma patients. Furthermore, we confirmed the expression of CBX3 on clinic pathological specimens by immunohistochemistry.
Results: The expression levels of CBX1/3/5/8 were significantly elevated in PAAD tissues, and the high expression of CBX1/5/6/7 was associated with the tumor stage of patients. Higher mRNA expression of CBX2/6/7 and CBX8 were significantly associated with favorable OS of pancreatic cancer patients, while higher expression of CBX3 was significantly associated with short OS. We verified the high expression of CBX3 in pancreatic cancer tissues on clinicopathological specimens. Multivariate logistic analysis demonstrated that high mRNA expressions of CBX3 and low expression of CBX8 were independent risk factors for shorter survival of pancreatic carcinoma patients. The functions of CBXs and its neighboring proteins are mainly related to negative regulation of cell cycle process, PcG protein complex, histone binding and regulating pluripotency of stem cells signaling pathways. We also found that the expression of CBXs was significantly correlated with immune infiltrates.
Conclusions: Our study may provide new insights into the selection of immunotherapeutic targets and prognostic biomarkers and revealed that CBX3/8 may represent a clinically useful biomarker for predicting overall survival in patients with PAAD.