Transcriptomic Analysis of Metastatic Colorectal Tumor with Low Mutational Burden

Abstract

Objective: To identify potential drug targets for metastasis colorectal cancer (CRC) patients with low mutational burden by examining differences in immune-related gene expression. Methods: For this study, 623 samples were collected from The Cancer Genome Atlas (TCGA) database, comprising tumor mutational burden (TMB), RNA sequencing (RNA-Seq), and clinical data. Differential gene expression analysis, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the identified genes were conducted using the R package. Additionally, a comparative analysis of immune infiltrating cell composition in metastatic and non-metastatic groups was performed. Hub genes, exhibiting high levels of interaction, were selected using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. The Drug Gene Interaction Database (DGIdb) was then utilized to estimate drugs targeting the identified hub genes. Results: The transcriptome data of 326 colorectal cancer patients with low TMB were analyzed, comprising 58 patients with metastasis and 268 patients without metastasis. Among the differential expression in 1,111 genes for patients with metastasis compared to those without metastasis, 733 genes were upregulated, and 378 genes were downregulated. KEGG and GO enrichment analysis indicated significant differences in gene expression in CRC metastatic patients with low TMB compared to non-metastasis patients with low TMB. Enriched pathways included humoral immuneresponse, immunoglobulin production, and regulation of AMPA receptor activity. Two genes related to interleukin-12 were identified through secondary enrichment for immune-related genes. Analysis of tumor-infiltrating immune cell data revealed significant differences in memory-activated T cell CD4 and T cell CD8. Conclusions: This analysis of RNA sequencing data and immune-filtrating cell data revealed significant differences between metastatic colorectal cancer patients with low TMB and their non-metastatic counterparts. These distinctions suggest the possibility of identifying more effective drugs or therapies for metastatic colorectal cancer patients with low TMB.