AUTHOR=Yu Tao , Li Dan , Zeng Zhi , Xu Xu , Zhang Haiming , Wu Jie , Song Wei , Zhu Hua 

TITLE=INSC Is Down-Regulated in Colon Cancer and Correlated to Immune Infiltration

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.821826

DOI=10.3389/fgene.2022.821826

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> 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<sup>+</sup> T cells, macrophages, DCs, and their marker sets in COAD.</p><p><bold>Conclusion:</bold> INSC was provided with prognostic value in COAD and related to immune invasion.</p>