Liu Jun, Zhang Shanqiang, Dai Wenjie, Xie Chongwei, Li Ji-Cheng
Medical Research Center, Yue Bei People's Hospital, Shantou University Medical College, Shaoguan, China.
Institute of Cell Biology, Zhejiang University, Hangzhou, China.
Front Oncol. 2021 Jan 14;10:586414. doi: 10.3389/fonc.2020.586414. eCollection 2020.
SLC41A3, as a member of the 41 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.
溶质载体家族41成员之一的SLC41A3参与镁的转运。SLC41A3在癌症预后和免疫调节中的作用鲜有报道。本研究旨在分析SLC41A3在泛癌中的表达状况及预后意义。SLC41A3的mRNA表达谱来自癌症基因组图谱(TCGA)、基因型-组织表达(GTEx)、布罗德研究所癌症细胞系百科全书(CCLE)以及国际癌症基因组联盟(ICGC)。采用Cox回归和Kaplan-Meier分析评估SLC41A3在泛癌中的预后价值。此外,利用TCGA数据库的数据计算SLC41A3表达与免疫细胞浸润、免疫检查点、错配修复(MMR)、DNA甲基转移酶(DNMT)、肿瘤突变负担(TMB)以及微卫星不稳定性(MSI)之间的相关性。结果显示,SLC41A3在肾透明细胞癌(KIRC)中表达下调,且与总体生存率低和肿瘤特异性死亡率相关。然而,SLC41A3在肝细胞癌(LIHC)中表达上调,Cox回归分析结果显示SLC41A3是LIHC预后的独立因素。同时,构建了一个包含SLC41A3和分期的列线图,该列线图对LIHC患者的总体生存具有良好的预测能力。此外,相关性分析表明SLC41A3与多种癌症中的TMB、MSI、MMR、DNMT以及免疫细胞浸润显著相关。总体生存和疾病特异性生存分析显示,SLC41A3表达与免疫细胞评分、TMB和MSI的联合与腺样囊性癌(ACC)、LIHC和葡萄膜黑色素瘤(UVM)患者的临床结局显著相关。因此,我们提出SLC41A3可能作为一种潜在的癌症预后生物标志物。