Zhao Qiaoyun, Zhao Rulin, Song Conghua, Wang Huan, Rong Jianfang, Wang Fangfei, Yan Lili, Song Yanping, Xie Yong
Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, No.17, Yongwai Zheng Street, Donghu District, Nanchang, 330000, Jiangxi, China.
Laboratory of Biochemistry and Molecular Biology, Jiangxi Institute of Medical Sciences, Nanchang 330000, Jiangxi Province, China.
J Cancer. 2021 Jan 1;12(5):1343-1355. doi: 10.7150/jca.50370. eCollection 2021.
Insulin-like growth factor binding protein-7 (IGFBP7) contributes to multiple biological processes in various tumors. However, the role of IGFBP7 in gastric cancer (GC) is still undetermined. The study aims to explore the role of IGFBP7 in GC via an integrated bioinformatics analysis. IGFBP7 expression levels in GC and its normal gastric tissues were analyzed using multiple databases, including the Tumor Immune Estimation Resource (TIMER), Oncomine, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, as well as by our clinical gastric specimens. The methylation analysis was conducted with MEXPRESS, UALCAN and Xena online tools. The survival analysis was conducted using the Kaplan-Meier Plotter and Gene Expression Profiling Interactive Analysis (GEPIA) databases. Coexpressed genes of IGFBP7 were selected with the cBioPortal tool and enrichment analysis was conducted with the clusterProfiler package in R software. Gene set enrichment analysis (GSEA) was performed to explore the IGFBP7-related biological processes involved in GC. Correlations between IGFBP7 and immune cell infiltrates were analyzed using the TIMER database. IGFBP7 expression was significantly upregulated in GC and correlated with stage, grade, tumor status and infection. High IGFBP7 expression and low IGFBP7 methylation levels were significantly associated with short survival of patients with GC. Univariate and multivariate analyses revealed that IGFBP7 was an independent risk factor for GC. The coexpressed genes , , , and predicted unfavorable outcomes of GC. Enrichment analysis showed that the coexpressed genes were involved in extracellular matrix (ECM)-related processes. GSEA indicated that IGFBP7 was positively related to ECM and inflammation-related pathways. TIMER analysis indicated that the mRNA level of IGFBP7 was strongly correlated with genes related to various infiltrating immune cells in GC, especially with gene markers of tumor associated macrophages (TAMs). Increased IGFBP7 expression correlates with poor prognosis and immune cell infiltration in GC, which might be a potential biomarker for the diagnosis of GC.
胰岛素样生长因子结合蛋白7（IGFBP7）在多种肿瘤的多个生物学过程中发挥作用。然而，IGFBP7在胃癌（GC）中的作用仍不明确。本研究旨在通过综合生物信息学分析探讨IGFBP7在胃癌中的作用。使用多个数据库，包括肿瘤免疫评估资源（TIMER）、Oncomine、癌症基因组图谱（TCGA）和基因表达综合数据库（GEO），以及我们的临床胃标本，分析IGFBP7在胃癌及其正常胃组织中的表达水平。使用MEXPRESS、UALCAN和Xena在线工具进行甲基化分析。使用Kaplan-Meier Plotter和基因表达谱交互式分析（GEPIA）数据库进行生存分析。使用cBioPortal工具选择IGFBP7的共表达基因，并使用R软件中的clusterProfiler包进行富集分析。进行基因集富集分析（GSEA）以探索胃癌中涉及的IGFBP7相关生物学过程。使用TIMER数据库分析IGFBP7与免疫细胞浸润之间的相关性。IGFBP7表达在胃癌中显著上调，且与分期、分级、肿瘤状态和感染相关。高IGFBP7表达和低IGFBP7甲基化水平与胃癌患者的短生存期显著相关。单因素和多因素分析显示IGFBP7是胃癌的独立危险因素。共表达基因 、 、 、 和 预测胃癌的不良预后。富集分析表明共表达基因参与细胞外基质（ECM）相关过程。GSEA表明IGFBP7与ECM和炎症相关途径呈正相关。TIMER分析表明IGFBP7的mRNA水平与胃癌中各种浸润免疫细胞相关基因密切相关，尤其是与肿瘤相关巨噬细胞（TAM）的基因标志物密切相关。IGFBP7表达增加与胃癌的不良预后和免疫细胞浸润相关，这可能是胃癌诊断的潜在生物标志物。
