Abstract
SLC41A3, as a member of the 41st family of solute carriers, participates in the transport of magnesium. The role of SLC41A3 in cancer prognosis and immune regulation has rarely been reported. This study was designed to analyze the expression status and prognostic significance of SLC41A3 in pan-cancers. The mRNA expression profiles of SLC41A3 were obtained from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx), the Broad Institute Cancer Cell Line Encyclopedia (CCLE), and the International Cancer Genome Consortium (ICGC). The Cox regression and Kaplan-Meier analyses were used to evaluate the prognostic value of SLC41A3 in pan-cancer. Furthermore, the correlation between SLC41A3 expression and immune cells infiltration, immune checkpoint, mismatch repair (MMR), DNA methyltransferase (DNMT), tumor mutation burden (TMB), and microsatellite instability (MSI) were calculated using data form TCGA database. The results showed that the expression of SLC41A3 was down-regulated in kidney renal clear cell carcinoma (KIRC), and was associated with poor overall survival and tumor-specific mortality. Whereas, the expression of SLC41A3 was up-regulated in liver hepatocellular carcinoma (LIHC), and the results of Cox regression analysis revealed that SLC41A3 was an independent factor for LIHC prognosis. Meanwhile, a nomogram including SLC41A3 and stage was built and exhibited good predictive power for the overall survival of LIHC patients. Additionally, correlation analysis suggested a significant correlation between SLC41A3 and TMB, MSI, MMR, DNMT, and immune cells infiltration in various cancers. The overall survival and disease-specific survival analysis revealed that the combined SLC41A3 expression and immune cell score, TMB, and MSI were significantly associated with clinical outcomes in ACC, LIHC, and UVM patients. Therefore, we proposed that SLC41A3 may serve as a potential prognostic biomarker for cancer.
Highlights
Worldwide, cancer has seriously jeopardized public health, and the incidence and mortality of cancer are rapidly increasing every year [1]
The results showed that SLC41A3 expressions were the lowest in the blood and liver tissue compared with other tissues, while the highest expressions of SLC41A3 were found in the testis, uterus and ovary tissues compared to other tissues (Kruskal-Wallis test P
We evaluated the mRNA expression of SLC41A3 in twenty-two cancer cell lines from the Cell Line Encyclopedia (CCLE) database, and the results revealed that the expression levels of SLC41A3 varied significantly among cancer cell lines [KruskalWallis test P
Summary
Cancer has seriously jeopardized public health, and the incidence and mortality of cancer are rapidly increasing every year [1]. Among the most common cancers, lung, pancreatic, and liver cancers are responsible for high mortality rate worldwide [1]. Despite considerable effort has been made to enhance the diagnosis and treatment of cancer, the 5-year survival rate is still disheartening [2]. SLC41A3 is a member of the 41st family of solute carriers, which can play a significant role in the magnesium (Mg2+) transport [7,8,9]. It has been demonstrated that aberrant expression of SLC41A3 is associated with various diseases, including hypertension, Parkinson’s disease, and nephronophthisis [11, 12]. The role of SLC41A3 in pan-cancer remains unclear
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