Systematic Pan-Cancer Analysis Identifies SLC31A1 as a Biomarker in Multiple Tumor Types

Abstract

Background Solute Carrier Family 31 Member 1 (SLC31A1) has recently been identified as a cuproptosis-regulatory gene. Recent studies have indicated that SLC31A1 may play a role in colorectal and lung cancer tumorigenesis. However, the role of SLC31A1 and its cuproptosis-regulatory functions in multiple tumor types remains to be further elucidated. Methods In this study, we used some website tools such as HPA, GEPIA2 and cBioPortal to estimate the expression, genetic alteration and prognostic in multiple cancer types. TIMER2 was used to evaluate the cancer-associated fibroblast infiltration. DAVID and BioGRID were used to conduct functional analysis and constructe the PPI network, respectively. Results In general, the TCGA datasets showed increased SLC31A1 expression in tumor tissues compared with non-tumor tissues in most tumor types. In patients with tumor types including Adrenocortical Carcinoma (ACC), Low-Grade Glioma (LGG), or Mesothelioma (MESO), higher SLC31A1 expression was correlated with shorter overall survival (OS) and disease-free survival (DFS). Moreover, the expression of SLC31A1 was also implicated to be positively correlated with the infiltration of fibroblasts into tumor tissues. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that SLC31A1 co-expressed genes were involved in protein binding, integral components of the membrane, metabolic pathways, and protein processing in the endoplasmic reticulum. Protein-protein interaction network analysis showed that SLC31A1 interacted with Copper Chaperone for Superoxide Dismutase (CCS), and Erb-B2 Receptor Tyrosine Kinase 3 (ERBB3), which had been known to be associated with copper transportation and tumorigenesis. Conclusions These findings demonstrated that SLC31A1 is associated with multiple tumor types and prognosis. SLC31A1 may be a potential key biomarker and therapeutic target in cancers. As a result, it will be a novel new therapy for cancer patients to improve the prognosis of cancer patients.

Cuproptosis in cancer: biological implications and therapeutic opportunities

“…This increased expression was shown to correlate with shorter overall and diseasefree survival [154]. Furthermore, SLC31A1 expression levels are positively associated with immune cell infiltration [154]. This observation was also replicated in breast cancer samples, where SLC31A1 upregulation predicted a dismal prognosis and was associated with a suppressed immune response and metabolic pathways [151,152].…”

“…Through the analysis of websites and datasets, Kong and colleagues observed that SLC31A1 expression is elevated in most tumor types, including adrenocortical carcinoma, mesothelioma, and LGG, compared with nontumor tissues. This increased expression was shown to correlate with shorter overall and diseasefree survival [154]. Furthermore, SLC31A1 expression levels are positively associated with immune cell infiltration [154].…”

Cuproptosis-related Gene Slc31a1 Expression Correlates With the Prognosis and Tumor Immune Microenvironment in Glioma

“…Most genes, such as FDX1, have been studied in different cancers to different degrees [9][10][11][12]. Besides, we noticed that SLC31A1 had been studied in different cancers and strongly correlated with poor prognosis [13,14].…”

Copper metabolism and cuproptosis in human malignancies: Unraveling the complex interplay for therapeutic insights

“…In Bladder urothelial carcinoma (BLCA), Thyroid carcinoma (THCA), and Uveal melanoma (UVM), the analysis of survival plots between SLC31A1 expression patterns and the survival rate of patients suffering from cancer revealed that individuals having lower expression pattern of SLC31A1 shows better overall survival as compared to persons having higher SLC31A1 expression profile. According to the pan-cancer analysis by Ma et al to establish the correlation between SLC31A1 expression and tumor progression, atrocious overall survival was found in skin cutaneous melanoma, testicular germ cell tumors, adrenocortical carcinoma and tymoma with higher expression of SLC31A1 [ 80 ]. The negative correlation between the expression pattern of SLC31A1 and survival of patients indicates that enhanced copper intake is strongly linked to the development and spread of cancers, influencing the patient's expected lifespan.…”