The crosstalk between anoikis and epithelial-mesenchymal transition and their synergistic roles in predicting prognosis in colon adenocarcinoma

Jiahui Zhou; Sheng Yang; Dawei Zhu; Hao Li; Xinsheng Miao; Menghui Gu; Wei Xu; Yan Zhang; Wei Tang; Renbin Shen; Jianhua Zha; Jianhua Zhu; Zheng Yuan; Xinhua Gu

doi:10.3389/fonc.2023.1184215

The crosstalk between anoikis and epithelial-mesenchymal transition and their synergistic roles in predicting prognosis in colon adenocarcinoma

Front Oncol. 2023 Jun 7:13:1184215. doi: 10.3389/fonc.2023.1184215. eCollection 2023.

Authors

Jiahui Zhou¹, Sheng Yang^{2

3}, Dawei Zhu¹, Hao Li¹, Xinsheng Miao¹, Menghui Gu¹, Wei Xu¹, Yan Zhang¹, Wei Tang¹, Renbin Shen¹, Jianhua Zha¹, Jianhua Zhu¹, Zheng Yuan¹, Xinhua Gu¹

Affiliations

¹ Department of Gastrointestinal Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China.
² Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
³ Colorectal Institute of Nanjing Medical University, Nanjing, China.

Abstract

Anoikis and epithelial-mesenchymal transition (EMT) are significant phenomena occurring in distant metastasis of colon adenocarcinoma (COAD). A comprehensive understanding of their crosstalk and the identification of key genes are vital for treating the distant metastasis of COAD. The objective of this study was to design and validate accurate prognostic predictors for COAD patients based on the anoikis and EMT processes. We obtained gene signatures from various databases and performed univariate and multivariate Cox regression analyses, principal component analysis (PCA). The COAD patients were categorized into the worst prognosis group, the Anoikis Potential Index (API) Low + EMT Potential Index (EPI) High group and the others group. Then we utilized gene set enrichment analysis (GSEA) to identify differentially expressed genes and to establish a prognostic risk model. The model classified patients into high- or low-risk groups, with patients in the high-risk group displaying worse survival status. A nomogram was established to predict overall survival rates, demonstrating high specificity and sensitivity. Additionally, we connected the risk model to the tumor microenvironment (TME) using single-sample GSEA and the MCP counter tool, as well as evaluated the sensitivity to common chemotherapeutic drugs, such as Gefitinib and Gemcitabine. Lastly, cell and tissue experiments suggested a positive correlation among anoikis resistance, EMT, and liver/lung metastasis of COAD. This is the first study to comprehensively analyze the crosstalk between anoikis and EMT and offers new therapeutic targets for COAD metastasis patients.

Keywords: EMT; anoikis; colon adenocarcinoma; crosstalk; risk model.

Grants and funding

This work was supported by the Clinical study of the accurate laparoscopic surgical treatment of rectal cancer (Grant No. LCZX202111); the Key Medical Discipline Gastrointestinal Surgery of Suzhou (Grant No. SZXK202109).