PCID2 is highly expressed in gastric cancer and affects the prognosis by regulating cancer cell cycle and proliferation

Abstract

To investigate the expression of PCI Domain Containing 2 (PCID2) in gastric cancer, its effect on gastric cancer cell cycle and proliferation and the possible molecular mechanisms. We examined PCID2 expression levels in gastric cancer and adjacent tissues from 100 patients undergoing radical gastrectomy in our hospital between January, 2012 and December, 2016, and analyzed the correlation of PCID2 expression level with cancer progression and postoperative 5-year survival rate of the patients. GO enrichment analysis was performed to identify the possible pathways that mediated the effect of PCID2 in gastric cancer progression. The effects of lentivirus-mediated PCID2 knockdown and overexpression on cell proliferation and cell cycle were analyzed in gastric cancer MGC-803 cells and in nude mice. PCID2 was highly expressed in gastric cancer tissues and positively correlated with peripheral blood levels of CA19-9 and CEA (P < 0.01). In gastric cancer patients, a high PCID2 expression was associated with a significantly lowered postoperative 5-year survival rate (P < 0.001) as an independent risk factor for postoperative survival (HR: 2.987, 95% CI: 1.616-5.519). The sensitivity, specificity, and area under the curve of PCID2 for predicting postoperative 5-year survival were 76.74%, 75.44%, and 0.755 (P < 0.001), respectively. GO enrichment analysis suggested that PCID2 was associated with gastric cancer cell cycle progression. PCID2 overexpression in MGC-803 cells significantly promoted cell proliferation, G1/S phase transition, expressions of cyclin D1 and CDK6, and the growth of transplanted xenograft in nude mice (P < 0.05). The expressions of p27 and p16 were significantly lowered in gastric cancer tissues, and their expression levels were negatively regulated by PCID2 expression in MGC-803 cells (P < 0.05). PCID2 is highly expressed in gastric cancer tissues in close correlation with poor prognosis of the patients. High PCID2 expression promotes gastric cancer proliferation and cell cycle progression by inhibiting the expression of p27 and p16.