Expression Patterns And Prognostic Values Of Adhesive G-protein-coupled Receptors In Pancreatic Cancer

Objective: To systematically explore the expression patterns and prognostic values of 33 adhesive G-protein coupled receptors（a GPCRs）in pancreatic cancer.Methods: Oncomine,and GEPIA2 databases were explored to identify the commonly disregulated a GPCRs at the m RNA level in pancreatic cancer.K-M plotter database was used to assess the relationships between transcription levels and survival information to get prognostic biomakers.58 clinical samples were used to detect a GPCRs at protein level by immunohistochemstry and test its correlation with clinical characteristics.A series of cell experiments were performed in human pancreatic cancer cells to elucidate the biological functions of ADGRF4 and ADGRE5.GSEA analysis was used to explain the potential mechanisms of ADGRF4 and ADGRE5 in PC pathogenesis.Results: ADGRE5,ADGRA2,ADGRC3,ADGRF1,ADGRF4,ADGRG1,ADGRG6,ADGRL4,ADGRF5,ADGRL2,and ADGRE2 were commonly disregulated at m RNA level in pancreatic cancer in Oncomine and GEPIA2 databases.The survival curves from Kaplan-Meier plotter database showed that ADGRA2,ADGRC3,ADGRF1,ADGRG6,ADGRE5,and ADGRF4 were associated with overall survival.ADGRF4,ADGRE5,and ADGRC3 were highly expressed at the protein level in pancreatic cancer tissues,among which ADGRF4 and ADGRE5 were related to clinical characteristics.Downregulation of ADGRF4 and ADGRE5 suppressed the abilities of migration and proliferation of pancreatic cells in vitro.Gene Set Enrichment Analysis（GSEA）showed that ADGRE5 and ADGRF4 were associated with cell-cell or cell-matrix communications or ribosome biogenesis.Conclusion : ADGRE5,ADGRA2,ADGRC3,ADGRF1,ADGRF4,and ADGRG6 could be employed as innovative prognostic biomarkers.ADGRF4 and ADGRE5 could be employed as potential therapeutic targets which were associated with cell-matrix communications or ribosome biogenesis.