Comprehensive analysis of cuproptosis genes and cuproptosis-related genes as prognosis factors in esophageal squamous cell carcinoma

• Published in: Genomics (San Diego, Calif.) Calif.), 2023-11, Vol.115 (6), p.110732, Article 110732
• Main Authors: Wu, Zhisheng, Huang, Zexin, Zhou, Xiao, Gao, Chenmeng, Peng, Zhongte, Zheng, Xiaoqi, Zhang, Yifan, Du, Zepeng, Wu, Bingli
• Format: Article
• Language: English
• Subjects: Apoptosis; Carcinogenesis; Cell Transformation, Neoplastic; Cuproptosis; Esophageal Neoplasms - genetics; Esophageal squamous cell carcinoma; Esophageal Squamous Cell Carcinoma - genetics; Gene Expression; Homeodomain Proteins; Humans; Prognostic model; WGCNA
• ISSN: 0888-7543; 1089-8646; 1089-8646
• DOI: 10.1016/j.ygeno.2023.110732

Esophageal squamous cell carcinoma (ESCC) is a common invasive and pernicious cancer with a low five-year survival rate. To identify potential therapeutic targets, we first investigated the characteristics of cuproptosis genes (CUGs) in ESCC. The expression patterns of 10 CUGs (FDX1, LIPT1, LIAS, DLAT, DLD, PDHA1, PDHB, GLS, MTF1, and CDKN2A) were analyzed to identify ESCC-relevant targets. Weighted correlation network analysis (WGCNA) was performed to obtain CUG-related genes (CRGs). A total of seven differentially expressed genes were identified (FDX1, DLAT, LIAS, PDHB, MTF1, GLS, and CDKN2A). DLAT was upregulated in stage III, and LIPT1 was upregulated in N0 + N1 cancers. The high expression of CDKN2A, and PDHA1, was related to better overall survival, whereas the low expression of LIAS was related to better clinical outcomes. WGCNA was performed to get CUG-related genes (CRGs) and showed three key modules that related to FDX1, DLAT, and LIPT1. Moreover, CRGs (BTLA, CT47A1, and PRRX1) were selected to construct a risk score model in order to predict the survival and prognosis of patients with ESCC. Additionally, the cuproptosis score based on CUGs and a nomogram constructed based on it helped accurately predict the prognosis of patients with ESCC; thus, maybe it can be used for the clinical diagnosis of ESCC. The results also showed that milciclib might inhibit the proliferation and migration of KYSE150 and KYSE510 cells by targeting CDKN2A. In conclusion, the abovementioned CUGs and CRGs play a crucial role in tumorigenesis and cancer progression in ESCC, indicating their potential as therapeutic targets. •Most CUGs (FDX1, DLAT, LIAS, PDHB, MTF1, GLS, CDKN2A) are differentially expressed in tumor tissues and DLAT expression was upregulated in stage III.•Cuproptosis risk score was an independent prognostic factor for patients with ESCC.•Two clusters identified by the NMF clustering based the expression of the 10 CUGs have different immune infiltrations.•Milciclib might inhibit the proliferation and migration of ESCC cells by targeting CDKN2A and increase cell death.