PDGFRB knockdown rescues the efficacy of chemotherapy in metastatic gastric cancer patients

Abstract

IntroductionThis study aimed to investigate the effect of PDGFRB on the efficacy of neoadjuvant chemotherapy (NAC) in metastatic gastric cancer (MGC).Material and methodsThe data from Gene Expression Omnibus (GEO) were analyzed to screen differentially expressed genes (DEGs). PDGFRB expression in cells were assessed by qRT-PCR and immunohistochemistry. Transwell, MTT and colony form assays were applied to determine the abilities of cell migration, cell invasion and cell proliferation. The association of core gene and PI3K/AKT pathway were identified through STRING database and western blot detection. Differences in overall survival (OS) among different patients were analyzed through Kaplan-Meier survival curve and prognostic factors were analyzed by Cox regression.ResultsHigh expression of PDGFRB and were found in gastric cancer through GEO data and MGC patients with combination chemotherapy resistance of docetaxel, cisplatin and S-1 (DCS therapy). Furthermore, the down-regulation of PDGFRB by PDGFRB shRNA or sunitinib malate could decrease cell migration, cell invasion and cell proliferation in resistant cells. Those findings were verified by in vivo experiments. Meanwhile, PDGFRB overexpression was accompany with the activation of PI3K/AKT pathway. In addition, the OS of patients in highly expressed PDGERB group were lower than that in lowly PDGFRB expressed group and PDGFRB, TNM staging and differentiation degree were the prognostic factors for MGC patients.ConclusionsPDGFRB knockdown could rescue the efficacy of chemotherapy in MGC and PDGFRB could serve as a novel marker for the prognosis of MGC.