Identification of G-protein signaling modulator 2 as a diagnostic and prognostic biomarker of pancreatic adenocarcinoma: an exploration of its regulatory mechanisms

• Published in: Journal of gastrointestinal oncology 2021-06, Vol.12 (3), p.1164-1179
• Main Authors: Zhou, Xintong, Dang, Shengchun, Jiang, Huaji, Gu, Min
• Format: Article
• Language: English
• Subjects: Original
• ISSN: 2078-6891; 2219-679X
• DOI: 10.21037/jgo-21-224

BACKGROUNDPancreatic adenocarcinoma (PAAD) has a high rate of mortality. Unfortunately, it is difficult to diagnosis. This study aimed to develop a more in-depth understanding of the disease. METHODSA total of 177 patients with PAAD were recruited from The Cancer Genome Atlas (TCGA) database. Microarray analysis was performed to identify differentially expressed genes (DEGs) in PAAD. The microarray data were adapted to the ingenuity pathway analysis (IPA) for annotation and visualization, followed by protein-protein interaction (PPI) network analysis. In vitro transwell migration assays were conducted to explore the molecular and functional characteristics of pancreatic adenocarcinoma cells (PANC-1) with stable low expression of G-protein signaling modulator 2 (GPSM2). Expression of GPSM2 and the associated hub genes were detected by reverse transcription-quantitative polymerase chain reaction (qPCR). RESULTSThe overexpression of GPSM2 was proved in PAAD, as compared with the healthy tissues, as well as its correlation with history of chronic pancreatitis, T stage, TNM stage and tumor grade. We described it as an independent prognostic factor and found that it could influence the infiltration of immune cells in the tumor microenvironment. Silencing of GPSM2 restrained the and migration of the cells. Microarray analysis identified 1,631 DEGs in PAAD cells. The PPI network analysis identified hub genes including CD44, ITGB1, ITGB5, ITGA2, ITGA5, AKT1, EGFR, NRAS and MAP2K1, and their relationship with GPSM2 was confirmed by qPCR. CONCLUSIONSGPSM2 is a novel prognostic factor and therapeutic target for PAAD. GPSM2 promoted the migration of pancreatic adenocarcinoma cells .Targeting GPSM2 and its downstream genes may prolong the survival time of patients with PAAD.