Single-Cell Transcriptomic Profiling Reveals T-Cell Functional Shifts in Primary Versus Metastatic Colorectal Cancer

Colorectal cancer (CRC) develops in the colon or rectum and is the second leading cause of cancer-related mortalities, with high rates of liver metastasis (LM). The tumor immune microenvironment (TIME) of primary CRC and LM-CRC is immunosuppressive, leading to T-cell dysfunction. Hence, this study employed computational techniques to unravel the novel T-cell-specific biomarkers being dysregulated due to niche-specific cancer cell signaling. A single-cell RNA sequencing (scRNA-seq) analysis of primary and LM CRC was performed, followed by identifying differentially expressed genes (DEGs) of T-cells. Subsequently, excluding common genes among both niches (primary CRC and LM-CRC), unique genes of T-cells were selected, and enriched Reactome pathways were identified. Moreover, the top-5 hub-genes of T-cells were identified by mapping the interactions of pathway genes in both niches. Lastly, novel hub-genes were selected after their expression validation in independent scRNA-seq datasets. The novel hub-genes, being dysregulated due to distinct cancer cell signals in respective niches, indicated to be implicated in the dysfunction of niche-specific T-cells, providing potential targets for immunotherapies. However, further larger cohorts are required, and clinical validation is essential to validate the therapeutic relevance of identified novel biomarkers.