Comprehensive Transcriptomic Analysis Reveals Prognostic Value of an EMT-Related Gene Signature in Colorectal Cancer

Area of Science:

• Oncology
• Molecular Biology
• Bioinformatics

Background:

• Lymph node metastasis (LNM) significantly impacts colorectal cancer (CRC) recurrence and patient survival.
• The epithelial-mesenchymal transition (EMT) pathway is implicated in cancer progression and metastasis.

Purpose of the Study:

• To identify and validate an EMT-related gene signature for predicting LNM and prognosis in CRC.
• To explore the functional role of EMT-associated genes in CRC proliferation and metastasis.
• To develop prognostic nomograms for clinical decision-making in CRC.

Main Methods:

• Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) were employed.
• An EMT-related gene signature was developed using LIMMA and LASSO Cox regression on a discovery cohort (489 CRC patients).
• Validation was performed on six independent datasets (1,045 CRC patients) with stratification analysis, alongside in vitro and in vivo functional studies.

Main Results:

• The EMT signaling pathway was identified as highly relevant to LNM in CRC.
• The developed EMT-related gene signature accurately stratified CRC patients into high- and low-risk groups.
• Functional analyses suggested that EMT-signature-associated genes play a role in CRC proliferation and metastasis.

Conclusions:

• An EMT-related gene signature holds significant prognostic value for predicting postoperative recurrence in CRC patients.
• This signature serves as a potential prognostic and therapeutic biomarker for CRC.
• Prognostic nomograms integrating the signature and clinical factors can aid in patient management and decision-making.