Comprehensive Transcriptome and miRNome Profiling in Metachronous Colorectal Liver Metastasis: Insight Into the...

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Colorectal cancer frequently metastasizes to the liver, but the molecular characteristics of these liver metastases remain largely unknown.
• Understanding the hepatic microenvironment's influence on metastatic colorectal cancer is crucial for developing targeted treatments.

Purpose of the Study:

• To investigate the transcriptome and miRNome of metachronous colorectal liver metastasis (mCLM) within the liver.
• To identify deregulated genes, microRNAs (miRNAs), pathways, and their clinical relevance in mCLM.
• To explore novel miRNA-mRNA interactions and their prognostic implications.

Main Methods:

• RNA sequencing was performed on 36 mCLM and adjacent non-malignant liver tissue pairs.
• Differential gene and miRNA expression analysis, gene set enrichment analysis, and consensus molecular subtype (CMS) classification were employed.
• miRNA-mRNA interactions were analyzed through co-expression, correlation, and survival analyses, with validation using multiMiR and real-time PCR.

Main Results:

• 1809 genes and 108 miRNAs were upregulated, while 1639 genes and 92 miRNAs were downregulated in mCLM.
• Upregulated genes were linked to epithelial-to-mesenchymal transition and cell cycle pathways.
• Novel miRNA-mRNA interactions were identified, with several showing prognostic relevance in patient cohorts.

Conclusions:

• The study uncovers a complex molecular landscape in mCLM within the hepatic microenvironment.
• Identified deregulated genes, miRNAs, and their interactions offer potential prognostic biomarkers.
• These findings suggest novel therapeutic targets for colorectal liver metastasis.