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.

Immune-related gene-based model predicts the survival of colorectal carcinoma and reflected various biological statuses

“…These reports suggest that the model based on these genes may reflect various statuses of colorectal cancer. It is notable that the genes were immunerelated genes, according to MSigDB, and SLC11A1 was reported to be associated with the microenvironment (Ma et al, 2022) in CRC and a similar result was found for CASP6 in gliomas (Guo et al, 2022). The other genes were also reported to reflect or influence the immune status of various types of cancers (Boggio et al, 2022).…”

“…ICOS, SPFQ, and FSTL1 were also reported to be correlated with proliferation, cell adhesion, and prognosis ( Zhang et al, 2016 ; Gu et al, 2018 ; Meng et al, 2022 ), while the studies were focused on gene polymorphism of LEP and CASP6 ( Choi et al, 2012 ; Liu et al, 2014 ). Notably, SLC11A1 was reported as a potential biomarker for prognosis and immune therapy efficiency ( Ma et al, 2022 ). These reports suggest that the model based on these genes may reflect various statuses of colorectal cancer.…”

Constructing and validating a risk model based on neutrophil‐related genes for evaluating prognosis and guiding immunotherapy in colon cancer

“…Both SLC11A1 and SLC2A3 are members of the solute carrier family and are responsible for encoding membrane transport proteins 50,51 . Reportedly, SLC11A1 not only predicts the prognosis of colorectal cancer and hepatocellular carcinoma 52,53 but also serves as a stratification indicator for immunotherapy or chemotherapy in glioma patients 54 . SLC2A3 exerts multiple biological functions in different cancers, including tumor EMT, ferroptosis, glycolytic reprogramming, drug resistance and immunity 55–59 .…”

Using machine learning methods to study the tumour microenvironment and its biomarkers in osteosarcoma metastasis

“…SLC11A1, also known as natural resistance-associated macrophage protein-1, is a member of the lysosomal carrier family. It has been reported to be associated with a poor prognosis in various gastrointestinal tumours [ 49 ]. These potential biomarkers can enhance our understanding of molecular mechanisms and show promise as targets for future therapeutic interventions.…”