Insulin receptor substrate 1(IRS1) is related with lymph node metastases and prognosis in esophageal squamous cell carcinoma

• Published in: Gene 2022-08, Vol.835, p.146651-146651, Article 146651
• Main Authors: Lei, Yufei, Jamal, Muhammad, Zeng, Xingruo, He, Hengjing, Xiao, Di, Zhang, Chengjie, Zhang, Xiaoyu, Tan, Haiyan, Xie, Songping, Zhang, Qiuping
• Format: Article
• Language: English
• Subjects: Actin gamma 2 (ACTG2); Calponin 1(CNN1); Overall survival; Relapse-free survival; Weighted gene co-expression network analysis
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2022.146651

•This study demonstrated that the lower expression of IRS1 was associated with lymph node metastasis (LNM) and poor prognosis of esophageal squamous cell carcinoma (ESCC).•Functional experiments of ESCC cell lines also showed that the overexpression of IRS1 significantly reduced the migration of ECA109 and EC9706 cells, but did not affect cell proliferation. IRS1 may be involved in LNM of ESCC as a tumor suppressor gene.•It was reported for the first time that ACTG2, SORBS1, MYH11 and CNN1 were down-regulated in tumor tissues compared with normal adjacent tissues in ESCC patients. The higher expression of ACTG2 and CNN1 was associated with poor RFS, suggesting that ACTG2 and CNN1 could be used as potential biomarkers to predict the prognosis of ESCC patients. Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer-related mortality globally with a high risk of lymph node metastasis (LNM). In this study, weighted gene co-expression network analysis (WGCNA) showed the identification of 10 modules among which the significant module (turquoise), including 1352 genes, was correlated with LNM. A group 52 overlapping differentially expressed genes (DEGs) was identified based on the comparison of turquoise module with GSE23400 and GSE20347 datasets. Using Ctyohubba plugin, we identified 7 hub genes (ACTG2, SORBS1, MYH11, CXCL12, CNN1, IRS1 and CXCL8). IRS1 displayed significant correlation with metastasis. The decreased expression of IRS1 was also a predictor of poor OS of ESCC patients whereas the hub genes namely ACTG2, MYH11, CXCL8, CXCL12, IRS1 and CNN1 were associated with RFS of ESCC patients. These findings suggest that the altered expression of these hub genes are associated with prognosis and thus can be used as potential biomarkers for ESCC. Moreover, immunohistochemical staining and cell functional experiments displayed that the overexpression of IRS1 was negatively associated with metastasis in ESCC. In general, our research revealed several novel genes in ESCC especially the association of IRS1 with LNM in ESCC, which could provide novel insights into the initiation and progression of ESCC.