Chen Jun, Wang Hongli, Peng Fang, Qiao Haiyan, Liu Linfeng, Wang Liang, Shang Bingbing
Laboratory Animal Center, Dalian Medical University, Dalian, 116044, Liaoning Province, People's Republic of China.
Cardiology Department, The Second Hospital of Dalian Medical University, Dalian, 116023, Liaoning Province, People's Republic of China.
Int J Gen Med. 2022 Feb 15;15:1547-1564. doi: 10.2147/IJGM.S348296. eCollection 2022.
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.
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.
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.
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.
已观察到anoctamin 1（ANO1）在胃肠道和肺上皮细胞以及多种癌症中过度表达。尽管Ano1参与结直肠癌（CRC）的预后，但它在转移性CRC中的作用机制尚未完全阐明。
在从癌症基因组图谱（TCGA）数据库获得的样本中评估Ano1的表达。然后，我们使用基因本体（GO）富集、京都基因与基因组百科全书（KEGG）通路分析、基因集富集分析（GSEA）、基因集变异分析（GSVA）和加权相关网络分析（WGCNA）来确定Ano1的功能。此外，使用随机生存森林、Cox多变量分析、Kaplan Meier分析和ROC来确定Ano1对CRC患者临床结局的预测价值。最后，使用苏木精-伊红（HE）染色、免疫组织化学（IHC）分析和qRT-PCR来探索Ano1基因在CRC组织中的表达。
CRC中Ano1的表达水平显著升高，预后较差。上调基因比例较高的模块往往与Ano1高表达呈正相关。KNG1、GNG4、F2、POSTN、THBS2、SPP1和FGA被确定为蛋白质-蛋白质相互作用（PPI）网络的枢纽蛋白。热图显示，Ano1高表达组的表达水平与免疫浸润显著负相关。HE染色、免疫组织化学（IHC）分析和qRT-PCR也证实了CRC组织样本中Ano1基因过表达。
Ano1高表达与结直肠癌患者的不良预后密切相关。Ano1可能参与CRC的转移和进展以及免疫调节。总之，Ano1可作为潜在的预后生物标志物和CRC治疗的新靶点。
