The impact of SLC10A3 on prognosis and immune microenvironment in colorectal adenocarcinoma

Abstract

Background SLC10A3, a gene upregulated in pan-cancer, lacks full understanding regarding its prognostic implications and association with immune infiltration in colorectal cancer (CRC). This study comprehensively analyzed SLC10A3 in CRC, evaluating its prognostic significance and influence on the tumor's immune microenvironment. Methods Transcriptomic data from TCGA were obtained to compare SLC10A3 expression in both colorectal cancer (CRC) and normal tissues. Prognostic value was assessed for overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). DNA methylation patterns of SLC10A3 and correlation with DNA mismatch repair (MMR) were explored. Genetic alterations in SLC10A3 were scrutinized. The study also delved into the influence of SLC10A3 on the immune microenvironment of CRC, including immune cell infiltration and chemokines. Involvement of cancer-associated fibroblasts (CAFs) was explored. Methylation status of specific CpG islands in the SLC10A3 gene correlated with CRC patient prognosis. CRC tissue microarray was performed to verify the expression of SLC10A3 and its relationship with prognosis. Results The research revealed that SLC10A3 is significantly upregulated in CRC and holds promise as a potential diagnostic marker. Elevated SLC10A3 expression was linked to poorer OS, DSS, and PFI. Methylation patterns of SLC10A3 displayed prognostic relevance, and genetic alterations in the gene were identified. SLC10A3 was shown to impact the immune microenvironment, with significant correlations observed between its expression and various immune cell types, chemokines, and markers associated with CAFs. Furthermore, an inverse relationship between SLC10A3 and MMR molecules was established. Methylation status of specific CpG islands within the SLC10A3 gene was associated with CRC patient prognosis. Tissue microarray showed that SLC10A3 was highly expressed in CRC and significantly correlated with poor prognosis. Conclusion The study underscores the importance of elevated SLC10A3 in CRC, associating it with decreased survival and immune infiltration, proposing it as a diagnostic biomarker and appealing immunotherapy target, given its significant overexpression and influence on the immune microenvironment and prognosis through methylation patterns. Graphical Abstract

Integrated profiling identifies DXS253E as a potential prognostic marker in colorectal cancer

“…Moreover, they suggested that SLC10A3 is a possible therapeutic target for LGG [ 41 ]. Furthermore, Wang et al’s study that analyzed public databases indicates that a high DXS253E expression predicts poor prognosis in CRC patients, and they propose that it could be used as an immunotherapy target in CRC given its significant influence on the immune microenvironment [ 23 ]. Similarly, we found that CRC patients with higher DXS253E tumor expression exhibit worse outcomes in respect to both OS and DSS, suggesting that DXS253E can serve as a predictor of CRC prognosis.…”

“…Recent studies have indicated that DXS253E is associated with the infiltration of immune cells in liver cancer [ 22 ]. Similarly, Wang et al analyzed public databases and identified that DXS253E influences the immune microenvironment and is related to poor prognosis in patients with CRC [ 23 ]. However, the exact role of DXS253E in CRC remains to be further determined through the specific experiments.…”