Yu Tao, Li Dan, Zeng Zhi, Xu Xu, Zhang Haiming, Wu Jie, Song Wei, Zhu Hua
Department of Oncology, Integrated Chinese and Western Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, China.
Front Genet. 2022 May 19;13:821826. doi: 10.3389/fgene.2022.821826. eCollection 2022.
Previous studies have verified that Inscuteable Spindle Orientation Adaptor Protein (INSC) can regulate cell proliferation and differentiation in the developing nervous system. It also plays an important role in spindle orientation during mitosis and asymmetric division of fibroblasts and participates in the process of stratification of the squamous epithelium. The role and potential mechanism of INSC in the development of colonic adenocarcinoma (COAD) have not been fully understood. This study aimed at exploring the prognostic value of INSC in COAD and the correlation of its expression with immune infiltration. The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) project, Gene Expression Profiling Interactive Analysis (GEPIA), and Gene Expression Omnibus (GEO) database were used to analyze the expression of INSC in COAD. The INSC protein expression level was analyzed by immunohistochemistry staining and the Human Protein Atlas (HPA) database. The diagnostic and prognostic values of INSC in COAD patients were analyzed using receiver operating characteristic (ROC) and Kaplan-Meier (KM) survival curves. In order to understand whether INSC is an independent prognostic factor, we used univariable and multivariate Cox analyses to analyze INSC expression and several clinical characteristics with survival. We use STRING analysis to find INSC-related proteins and related biological events analyzed by Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. At last, GEPIA and the Tumor Immune Estimation Resource (TIMER) were employed to explore the relationship between INSC and immune infiltrates and its marker gene set. INSC was lower expressed in COAD tissues than in normal colon tissues, which was correlated with tumor stage. Patients with lower expression of INSC had shorter overall survival (OS). Moreover, univariable Cox analysis demonstrated that high expression of INSC was an independent prognostic factor for COAD. ROC analysis showed INSC was an accurate marker for identifying tumors from normal colon tissue, and the AUC of the curve was 0.923. Significant GO term analysis by GSEA showed that genes correlated with INSC were found to be enriched in several immune-related pathways. Specifically, INSC expression showed significant negative correlations with infiltration levels of B cells, CD4 T cells, macrophages, DCs, and their marker sets in COAD. INSC was provided with prognostic value in COAD and related to immune invasion.
以往的研究已经证实，无柄纺锤体定向衔接蛋白（INSC）可以调节发育中的神经系统中的细胞增殖和分化。它在有丝分裂期间的纺锤体定向以及成纤维细胞的不对称分裂中也发挥着重要作用，并参与鳞状上皮的分层过程。INSC在结肠腺癌（COAD）发生发展中的作用及潜在机制尚未完全明确。本研究旨在探讨INSC在COAD中的预后价值及其表达与免疫浸润的相关性。利用癌症基因组图谱（TCGA）、基因型-组织表达（GTEx）项目、基因表达谱交互分析（GEPIA）和基因表达综合数据库（GEO）分析INSC在COAD中的表达情况。通过免疫组织化学染色和人类蛋白质图谱（HPA）数据库分析INSC蛋白表达水平。采用受试者工作特征（ROC）曲线和Kaplan-Meier（KM）生存曲线分析INSC对COAD患者的诊断和预后价值。为了了解INSC是否为独立的预后因素，我们采用单因素和多因素Cox分析来分析INSC表达及几种临床特征与生存情况的关系。我们使用STRING分析来寻找与INSC相关的蛋白质，并通过基因本体论（GO）注释和京都基因与基因组百科全书（KEGG）分析来分析相关的生物学事件。最后，利用GEPIA和肿瘤免疫评估资源（TIMER）来探讨INSC与免疫浸润及其标志物基因集之间的关系。INSC在COAD组织中的表达低于正常结肠组织，且与肿瘤分期相关。INSC表达较低的患者总生存期（OS）较短。此外，单因素Cox分析表明，INSC高表达是COAD的独立预后因素。ROC分析显示，INSC是区分正常结肠组织与肿瘤组织的准确标志物，曲线下面积（AUC）为0.923。基因集富集分析（GSEA）的显著GO术语分析表明，与INSC相关的基因在几个免疫相关途径中富集。具体而言，在COAD中，INSC表达与B细胞、CD4 T细胞、巨噬细胞、树突状细胞（DC）及其标志物集的浸润水平呈显著负相关。INSC在COAD中具有预后价值，并与免疫侵袭相关。
