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

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

  • Gene. 2022 Aug 15;835:146651. doi: 10.1016/j.gene.2022.146651.
Yufei Lei 1 Muhammad Jamal 1 Xingruo Zeng 1 Hengjing He 1 Di Xiao 1 Chengjie Zhang 1 Xiaoyu Zhang 1 Haiyan Tan 2 Songping Xie 3 Qiuping Zhang 4
Affiliations

Affiliations

  • 1 Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
  • 2 Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China. Electronic address: Thy71061@126.com.
  • 3 Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, China. Electronic address: songping0428@126.com.
  • 4 Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University, Wuhan 430071, China. Electronic address: qpzhang@whu.edu.cn.
Abstract

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.

Keywords

Actin gamma 2 (ACTG2); Calponin 1(CNN1); Overall survival; Relapse-free survival; Weighted gene co-expression network analysis.

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