综合分析铜中毒相关基因SLC31A1对人类癌症患者预后和肿瘤微环境的影响。
Comprehensive analysis of the effects of the cuprotosis-associated gene SLC31A1 on patient prognosis and tumor microenvironment in human cancer.
发表日期:2024 Feb 29
作者:
Guiqian Zhang, Ning Wang, Shixun Ma, Pengxian Tao, Hui Cai
来源:
Immunity & Ageing
摘要:
溶质载体家族31(铜转运蛋白),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,探索SLC31A1潜在的生物学功能和价值可以为肿瘤的靶向治疗提供新的方向。本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),以及使用肿瘤免疫估计资源 2.0 (TIMER2.0)、基因表达谱交互分析 (GEPIA)、阿拉巴马大学伯明翰分校癌症 (UALCAN) 数据分析门户进行 SLC31A1 在泛癌中的免疫细胞浸润,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,还对SLC31A1进行了单细胞水平测序和基因本体/京都基因和基因组百科全书(GO/KEGG)富集分析。最后,使用实时定量聚合酶链反应(RT-qPCR)和蛋白质印迹(WB)来验证SLC31A1在癌症(例如胃癌)中的表达。SLC31A1在大多数癌症组织中表达。在肾透明细胞癌(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)、乳腺浸润性癌(BRCA)、低级别胶质瘤(LGG)、间皮瘤(MESO)中) 和皮肤黑色素瘤 (SKCM) 中,SLC31A1 的低表达与良好的 OS 相关。在 ACC 中观察到 SLC31A1 扩增频率最高。此外,错义突变占突变类型的主要部分。截短突变 S105Y 可能是假定的癌症驱动因素。 SLC31A1影响癌症中的甲基化水平,并与TMB、MSI和各种免疫细胞的浸润水平相关。此外,单细胞测序结果表明SLC31A1与癌症中的多种生物学功能相关。最后,SLC31A1富集分析显示,SLC31A1相关基因主要富集于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点,可能具有预后价值。2024转化癌症研究。版权所有。
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.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.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.SLC31A1 may be a potential target related to cancer energy metabolism and may have prognostic value.2024 Translational Cancer Research. All rights reserved.