Comprehensive Analysis of Expression, Clinicopathological Association and Potential Prognostic Significance of RABs in Pancreatic Cancer

RAB proteins (RABs) represent the largest subfamily of Ras-like small GTPases that regulate a wide variety of endosomal membrane transport pathways. Their aberrant expression has been demonstrated in various malignancies and implicated in pathogenesis. Using The Cancer Genome Atlas (TCGA) database, we analyzed the differential expression and clinicopathological association ofRABgenes in pancreatic ductal adenocarcinoma (PDAC). Of the 62RABgenes analyzed, five(RAB3A, RAB26, RAB25, RAB21,andRAB22A) exhibited statistically significant upregulation, while five (RAB6B, RAB8B, RABL2A, RABL2B,andRAB32) were downregulated in PDAC as compared to the normal pancreas. Racially disparate expression was also reported forRAB3A, RAB25,andRAB26. However, no clear trend of altered expression was observed with increasing stage and grade, age, and gender of the patients. PDAC from occasional drinkers had significantly higher expression ofRAB21compared to daily or weekly drinkers, whereasRAB25expression was significantly higher in social drinkers, compared to occasional ones. The expression ofRABL2Awas significantly reduced in PDAC from diabetic patients, whereasRAB26was significantly lower in pancreatitis patients. More importantly, a significant association of high expression ofRAB21, RAB22A,andRAB25, and low expression ofRAB6B, RABL2A,andRABL2Bwas observed with poorer survival of PC patients. Together, our study suggests potential diagnostic and prognostic significance of RABs in PDAC, warranting further investigations to define their functional and mechanistic significance.