Identification of PEG10 and TSG101 as Carcinogenesis, Progression, and Poor-Prognosis Related Biomarkers for Gallbladder Adenocarcinoma

PEG10 is a transcriptional factor while TSG101 is involved in numerous cellular processes, including apoptotic resistance. Overexpression of PEG10 and TSG101 were observed in a variety of human cancers. However, their expression and clinical significance in gallbladder cancer (GBC) have not yet been identified. To understand the tumor biology of GBC at the molecular level, we examined PEG10 and TSG101 expression in 108 adenocarcinomas, 15 gallbladder polyps, 35 chronic cholecystitis tissues, and 46 peritumoral tissues by using immunohistochemistry. Overexpression of PEG10 and TSG101 was detected in gallbladder adenocarcinoma (48.1% and 47.2%, respectively). Conversely, there was less expression detected in the peritumoral tissues (19.6%), adenomatous polyps (13.3%), and gallbladder epithelium with chronic cholecystitis (5.1%) (p < 0.01, p < 0.05, and p < 0.01, respectively). Notably, the benign lesions with positive PEG10 and/or TSG101 expression showed moderately or severely atypical hyperplasia in gallbladder epithelium. The overexpression of PEG10 and TSG101 was significantly associated with differentiation, tumor mass, lymph node metastasis and invasion of adenocarcinoma. Univariate Kaplan-Meier analysis showed that overexpression of PEG10 (p = 0.041) and TSG101 (p = 0.025) was closely associated with decreased overall survival. Multivariate Cox regression analysis revealed that positive expression of PEG10 (p = 0.036) or TSG101 (p = 0.022) is a predictor of poor prognosis in gallbladder adenocarcinoma. Our study suggested that overexpression of PEG10 and TSG101 might be closely related to the carcinogenesis, progression, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma.