P2RX7 functions as a putative biomarker of gastric cancer and contributes to worse prognosis. Issue 9 (June 2019)

• Record Type: Journal Article
• Authors: Lili, Wang; Yun, Li; Tingran, Wei; Xia, Wu; Yanlei, Sun
• Is Part Of: Experimental biology and medicine. Volume 244:Issue 9(2019)
• Page Start: 734
• Page End: 742
• Publication Date: 2019-06
• Subjects: P2RX7 -- gastric cancer -- proliferation -- metastasis; Physiology -- Periodicals; Biology, Experimental -- Periodicals; Medicine, Experimental -- Periodicals; 610.72
• DOI: 10.1177/1535370219846492
• Languages: English
• ISSNs: 1535-3702

Abstract

P2RX7 has a vital role in promoting proliferation and metastasis and is relevant to worse prognosis in multiple tumors. Nevertheless, P2RX7's prognostic value and unambiguous effect in gastric cancer remain to be further explored. Our study showed that the expression of P2RX7 in human gastric tumor tissue ( n = 80) was significantly higher than that in normal human gastric tissue ( n = 20, different cohort). Abnormally high expression of P2RX7 was related to larger tumor size ( P = 0.0473), higher T stage ( P = 0.0367), and lymphatic metastasis ( P = 0.0056). Kaplan–Meier analysis showed that higher expression of P2RX7 was associated with worse overall survival and disease-free survival in gastric cancer patients. Additionally, downregulation of P2RX7 by a specific shRNA suppressed the proliferation and metastasis of gastric cancer cells, while ectopic overexpression P2RX7 had opposite effects. P2RX7 modulated ERK1/2 and Akt pathways and epithelial–mesenchymal transition markers such as E-cadherin, N-cadherin, vimentin, and snail. All in all, our results suggest that P2RX7 represents a prognostic biomarker of patients with gastric cancer and show the importance of P2RX7 as a putative biomarker in gastric cancer. Impact statement: The mechanism of gastric cancer is highly complex, accompanied by a variety of genetic abnormalities. It is of great significance to elucidate the pathogenesis of gastric cancer, find its markers and therapeutic targets in the fight against this fatal disease. In this study, we identified P2RX7 as a putative target of gastric cancer, which was overexpressed in gastric cancer tissues and had relationship with worse prognosis. We also elucidated the roles of P2RX7 on the growth and metastasis of gastric cancer cells, and explored the relationship between it and ERK1/2 pathway, Akt pathway, and epithelial–mesenchymal transition. Our findings begin to offer useful insights into the mechanism of gastric cancer progression and provide clues to novel therapy strategies.