Wu Lingyun, Zhu Xinli, Yan Danfang, Tang Mengmeng, Ma Chiyuan, Yan Senxiang
Department of Radiation Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Front Oncol. 2021 Mar 22;11:626883. doi: 10.3389/fonc.2021.626883. eCollection 2021.
Despite improvements reported in diagnosis and treatments in recent decades, pancreatic cancer is still characterized by poor prognosis and low survival rate among solid tumors. Intensive interests have grown in exploring novel predictive biomarkers, aiming to enhance the efficiency in early detection and treatment prognosis. In this study, we identified the differentially expressed genes (DEGs) in pancreatic cancer by analyzing five gene expression profiles and established the functional modules according to the functional interaction (FI) network between the DEGs. A significant upregulation of the selected DEG, interferon (IFN)-induced transmembrane protein 1 (IFITM1), was evaluated in several bioinformatics online tools and verified with immunohistochemistry staining from samples of 90 patients with pancreatic cancer. Prognostic data showed that high expression of IFITM1 associated with poor survival, and multivariate Cox regression analysis showed IFITM1 was one of the independent prognostic factors for overall survival. Meanwhile, significant correlations of the expression of IFITM1 and the infiltration of immune cells were found by TIMER. Furthermore, a higher level of IFITM1 was assessed in pancreatic cancer cell lines compared to normal human pancreatic duct epithelial cells, and silencing IFITM1 in tumor cells remarkedly inhibited cancer tumorigenicity. Collectively, our findings suggested that IFITM1 might have promising utility for pancreatic cancer.
尽管近几十年来在胰腺癌的诊断和治疗方面有了一些进展,但胰腺癌在实体瘤中仍具有预后差和生存率低的特点。人们对探索新的预测生物标志物越来越感兴趣,旨在提高早期检测和治疗预后的效率。在本研究中,我们通过分析五个基因表达谱确定了胰腺癌中差异表达基因(DEGs),并根据DEGs之间的功能相互作用(FI)网络建立了功能模块。通过几个生物信息学在线工具评估了所选DEG——干扰素(IFN)诱导跨膜蛋白1(IFITM1)的显著上调,并通过对90例胰腺癌患者样本进行免疫组织化学染色进行了验证。预后数据显示,IFITM1高表达与生存率低相关,多因素Cox回归分析显示IFITM1是总生存的独立预后因素之一。同时,通过TIMER发现IFITM1表达与免疫细胞浸润存在显著相关性。此外,与正常人胰腺导管上皮细胞相比,胰腺癌细胞系中IFITM1水平更高,在肿瘤细胞中沉默IFITM1可显著抑制肿瘤发生。总的来说,我们的研究结果表明IFITM1在胰腺癌中可能具有潜在的应用价值。