Pancreatic cancer is one of the most serious digestive malignancies. At present, there is an extreme lack of effective strategies in clinical treatment. The purpose of this study is to identify key genes and pathways in the development of pancreatic cancer and provide targets for the treatment of pancreatic cancer. GSE15471 and GSE62165 were used to screen differentially expressed genes by GEO2R tool. Hub genes prognostic potential assessed using the GEPIA and Kaplan–Meier plotter databases. The drug susceptibility data of pan-cancer cell lines is provided by The Genomics of Drug Sensitivity in Cancer Project (GDSC). Finally, the effects of PI3K–Akt signaling pathway inhibitors on cell viability of pancreatic cancer cells were detected by cell proliferation and invasion assays. A total of 609 differentially expressed genes were screened and enriched in the focal adhesion, phagosome and PI3K–Akt signaling pathway. Of the 15 hub genes we found, four were primarily associated with the PI3K–Akt signaling pathway, including COL3A1, EGF, FN1 and ITGA2. GDSC analysis showed that mTOR inhibitors are very sensitive to pancreatic cancer cells with mutations in EWSR1.FLI1 and RNF43. Cell proliferation and invasion results showed that mTOR inhibitors (GSK2126458) can inhibit the proliferation of pancreatic cancer cells. This study suggested that the PI3K–Akt signaling pathway may be a key pathway for pancreatic cancer, our study uncovered the potential therapeutic potential of GSK2126458, a specific mTOR inhibitor, for pancreatic cancer.

中文翻译：

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生物信息学分析和药理实验发现GSK2126458具有抑制胰腺癌增殖的潜力

胰腺癌是最严重的消化系统恶性肿瘤之一。目前临床治疗极度缺乏有效策略。本研究的目的是鉴定胰腺癌发生发展的关键基因和通路，为胰腺癌的治疗提供靶点。GSE15471和GSE62165用于通过GEO2R工具筛选差异表达基因。使用 GEPIA 和 Kaplan-Meier 绘图仪数据库评估 Hub 基因的预后潜力。泛癌细胞系的药物敏感性数据由癌症药物敏感性基因组学项目（GDSC）提供。最后，通过细胞增殖和侵袭实验检测PI3K-Akt信号通路抑制剂对胰腺癌细胞活力的影响。共筛选并富集了粘着斑、吞噬体和PI3K-Akt信号通路中的609个差异表达基因。在我们发现的 15 个枢纽基因中，有 4 个主要与 PI3K-Akt 信号通路相关，包括 COL3A1、EGF、FN1 和 ITGA2。GDSC分析表明mTOR抑制剂对EWSR1.FLI1和RNF43突变的胰腺癌细胞非常敏感。细胞增殖和侵袭结果表明，mTOR抑制剂（GSK2126458）可以抑制胰腺癌细胞的增殖。本研究表明PI3K-Akt信号通路可能是胰腺癌的关键通路，我们的研究揭示了特异性mTOR抑制剂GSK2126458对胰腺癌的潜在治疗潜力。