Establishment and validation of the prognostic risk model based on the anoikis-related genes in esophageal squamous cell carcinoma

Ann Med. 2024 Dec;56(1):2418338. doi: 10.1080/07853890.2024.2418338. Epub 2024 Oct 23.

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) is a malignant condition in humans. Anoikis-related genes (ARGs) are crucial to cancer progression. Therefore, more studies on the relationship between ARGs and ESCC are warranted.

Methods: The study acquired ESCC-related transcriptome data from TCGA. Differentially expressed ARGs (DE-ARGs) were obtained by differential analysis and candidates were filtered out by survival analysis. Prognostic genes were determined by Cox and LASSO regression. A risk model was constructed based on prognostic gene expressions. An immune infiltration study was done to explain how these genes contribute to ESCC development. The IC50 test was adopted to assess the clinical response of chemotherapy drugs. Single cell analysis was performed on the GSE145370 dataset. Moreover, the prognostic gene expressions were detected by qRT-PCR.

Results: 53 DE-ARGs were screened and four candidate genes including PBK, LAMC2, TNFSF10 and KL were obtained. Cox and LASSO regression identified the two prognostic genes, TNFSF10 and PBK. Immuno-infiltration analysis revealed positive associations of PBK with Macrophages M0 cells, and TNFSF10 with Macrophages M1 cells. The IC50 values of predicted drugs, in the case of Tozasertib 1096 and WIKI4 1940, were significantly variant between risk groups. Single cell analysis revealed that TNFSF10 and PBK levels were higher in epithelial cells than in other cells. The prognostic genes expression results by qRT-PCR were compatible with the dataset analysis.

Conclusion: The study established an ARG prognosis model of ESCC. It provided a reference for the research of ARGs in ESCC.

Keywords: Oesophageal squamous cell carcinoma; anoikis; biomarker.

Publication types

  • Validation Study

MeSH terms

  • Anoikis* / genetics
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Esophageal Neoplasms* / genetics
  • Esophageal Neoplasms* / mortality
  • Esophageal Squamous Cell Carcinoma* / genetics
  • Esophageal Squamous Cell Carcinoma* / mortality
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Risk Assessment / methods
  • Transcriptome

Substances

  • Biomarkers, Tumor

Grants and funding

This work was funded by postdoctoral research grant of Henan Province (202003105) and Major Projects of Science and Technology Department of Anyang City (2023C01SF086)