Ano1 is a Prognostic Biomarker That is Correlated with Immune Infiltration in Colorectal Cancer

Abstract

Jun Chen,1,* Hongli Wang,2,* Fang Peng,3,* Haiyan Qiao,1 Linfeng Liu,1 Liang Wang,1 Bingbing Shang4 1Laboratory Animal Center, Dalian Medical University, Dalian, 116044, Liaoning Province, People’s Republic of China; 2Cardiology Department, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning Province, People’s Republic of China; 3Pathology Department, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning Province, People’s Republic of China; 4Emergency Department, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bingbing Shang; Liang Wang, Tel [phone], Email [email protected]; [email protected]: Anoctamin 1 (ANO1) has been observed to be overexpressed in gastrointestinal and pulmonary epithelial cells, as well as in a number of cancers. Although Ano1 is involved in the prognosis of colorectal cancer (CRC), its mechanism of action in metastatic CRC has not been fully elucidated.Methods: The expression of Ano1 was assessed in samples obtained from The Cancer Genome Atlas (TCGA) database. Then, we used Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene set enrichment analysis (GSEA), Gene set variation analysis (GSVA), and Weighted Correlation Network Analysis (WGCNA) to determine the functions of Ano1. Additionally, random survival forest, Cox multivariate analysis, Kaplan Meier analysis, and ROC were used to determine the predictive value of Ano1 on clinical outcomes in CRC patients. Finally, HE staining, immunohistochemical (IHC) analysis and qRT-PCR were used to explore the expression of the Ano1 gene in CRC tissue.Results: The expression level of Ano1 in CRC was significantly elevated, and the prognosis was poor. The modules with a higher proportion of upregulated genes tended to be positively correlated with Ano1-high. KNG1, GNG4, F2, POSTN, THBS2, SPP1 and FGA were identified as hub proteins of the PPI network. The heatmap showed that the expression level of the Ano1-high group was significantly negatively correlated with immune infiltrate. The overexpression of the Ano1 gene in CRC tissue samples was also confirmed by HE staining, immunohistochemical (IHC) analysis and qRT-PCR.Conclusion: High expression of Ano1 is closely related to a poor prognosis in patients with colorectal cancer. Ano1 may participate in the metastasis and progression, as well as the immune regulation of CRC. In summary, Ano1 can act as a potential prognostic biomarker and a novel target for CRC therapy.Keywords: ANO1, biomarker, colorectal cancer, prognosis, Immune infiltration

Keywords

• anoctamin-1 (ano1)
• biomarker
• colorectal cancer
• prognosis