SLC11A1 associated with tumor microenvironment is a potential biomarker of prognosis and immunotherapy efficacy for colorectal cancer

Abstract

Colorectal cancer (CRC) is one of the most lethal cancers of the digestive system. The tumor microenvironment (TME) plays a central role in the initiation and development of CRC. However, little is known about the modulation mechanism of the TME in CRC. In our study, we attempted to identify a biomarker related to the TME modulation that could serve as a potential prognostic biomarker for CRC. We identified differentially expressed genes between the ImmuneScore high/low and StromalScore high/low groups. Using univariate COX regression analysis and hub gene analysis (cytoHubba), SLC11A1 was identified as the only candidate gene for subsequent analysis. CIBERSORT, EPIC, MCPcounter, and immunogenic cell death were performed to evaluate the effect of SLC11A1 on the TME. We also collected samples and performed Real-time quantitative PCR to verify the expression levels of SLC11A1 in CRC and adjacent normal tissues. The IMvigor210 cohort, TIDE score, and immunophenoscore (IPS) were used to analyze the association between SLC11A1 and immunotherapy efficacy. SLC11A1 was highly expressed in CRC tissues compared with its expression in normal colorectal tissues and was associated with poor prognosis and advanced clinicopathological stages. Gene set enrichment analysis showed that TGF-β pathways, JAK-STAT pathways, and angiogenesis were significantly enriched in the high-SLC11A1 group. Single-cell analysis validated the correlation between SLC11A1 and the TME. Using CIBERSORT, EPIC, and MCPcounter algorithms, we found that there was more macrophage and fibroblast infiltration in the SLC11A1 high-expression group. Meanwhile, high-SLC11A1 patients had lower IPS scores, higher TIDE scores, and fewer immunotherapy benefits than those of low-SLC11A1 patients. In conclusion, SLC11A1 plays a crucial role in the TME and could serve as a potential biomarker for poor prognosis and immunotherapy efficacy in CRC.