■溶质载体家族31(铜运输机),成员1(SLC31A1)是维持细胞内铜浓度的关键因素,也是影响癌症能量代谢的重要因素。因此,探讨SLC31A1潜在的生物学功能和价值,可为肿瘤的靶向治疗提供新的方向。
■这项研究评估了基因表达水平,生存,临床病理,基因突变,甲基化水平,肿瘤突变负荷(TMB),微卫星不稳定性(MSI),以及使用肿瘤免疫评估资源2.0(TIMER2.0)在泛癌症中SLC31A1的免疫细胞浸润,基因表达谱交互式分析(GEPIA),阿拉巴马大学伯明翰分校(UALCAN)数据分析门户,和cBioPortal数据库。为了进一步了解SLC31A1在不同癌症中的潜在生物学机制,还进行了SLC31A1的单细胞水平测序和基因本体论/京都基因和基因组百科全书(GO/KEGG)富集分析。最后,实时定量聚合酶链反应(RT-qPCR)和蛋白质印迹(WB)用于验证SLC31A1在癌症中的表达,比如胃癌。
■SLC31A1在大多数癌组织中表达。在肾肾透明细胞癌(KIRC)中,SLC31A1的高表达与良好的总生存期(OS)相关,而在肾上腺皮质癌(ACC)中,乳腺浸润性癌(BRCA),低级别的神经胶质瘤(LGG),间皮瘤(MESO),皮肤黑色素瘤(SKCM),SLC31A1的低表达与OS良好相关。在ACC中观察到SLC31A1扩增的最高频率。此外,错义突变占突变类型的主要部分。截短突变S105Y可以是推定的癌症驱动因素。SLC31A1影响癌症中的甲基化水平,并与TMB相关。MSI,以及各种免疫细胞的浸润水平。此外,单细胞测序结果显示,SLC31A1与多种肿瘤生物学功能相关.最后,SLC31A1富集分析显示SLC31A1相关基因主要富集在线粒体基质和包膜囊泡中。RT-qPCR和WB结果与预测结果一致。
■SLC31A1可能是与癌症能量代谢相关的潜在靶标,可能具有预后价值。
UNASSIGNED: Solute carrier family 31 (copper transporter), member 1 (SLC31A1) is a key factor in maintaining intracellular copper concentration and an important factor affecting cancer energy metabolism. Therefore, exploring the potential biological function and value of SLC31A1 could provide a new direction for the targeted therapy of tumors.
UNASSIGNED: This study assessed gene expression levels, survival, clinicopathology, gene mutations, methylation levels, the tumor mutational burden (TMB), microsatellite instability (MSI), and the immune cell infiltration of SLC31A1 in pan-cancer using the Tumor Immune Estimation Resource 2.0 (TIMER2.0), Gene Expression Profiling Interactive Analysis (GEPIA), University of Alabama at Birmingham CANcer (UALCAN) data analysis portal, and cBioPortal databases. To further understand the potential biological mechanisms of SLC31A1 in different cancers, single-cell level sequencing and a Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) enrichment analysis of SLC31A1 were also performed. Finally, real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB) were used to validate the expression of SLC31A1 in cancers, such as gastric cancer.
UNASSIGNED: SLC31A1 was expressed in most cancer tissues. In kidney renal clear cell carcinoma (KIRC), the high expression of SLC31A1 was associated with good overall survival (OS), while in adrenocortical carcinoma (ACC), breast invasive carcinoma (BRCA), lower grade glioma (LGG), mesothelioma (MESO), and skin cutaneous melanoma (SKCM), the low expression of SLC31A1 was associated with good OS. The highest frequency of SLC31A1 amplification was observed in ACC. In addition, missense mutations accounted for a major portion of the mutation types. The truncation mutation S105Y may be a putative cancer driver. SLC31A1 affected methylation levels in cancer and was associated with the TMB, MSI, and the level of infiltration of various immune cells. Additionally, the single-cell sequencing results showed that SLC31A1 was associated with multiple biological functions in cancer. Finally, the SLC31A1 enrichment analysis revealed that the SLC31A1-related genes were mainly enriched in the mitochondrial matrix and envelope vesicles. The RT-qPCR and WB results were consistent with the predicted results.
UNASSIGNED: SLC31A1 may be a potential target related to cancer energy metabolism and may have prognostic value.