目的:癌症仍然是一个全球性的健康挑战,需要鉴定新的生物标志物和治疗靶标。角化,一种最近公认的与铜代谢有关的细胞死亡形式,为抗癌策略提供了一条有希望的途径。我们调查了SLC31A1的临床意义,SLC31A1是角化的关键调节因子,在多种癌症类型中,旨在阐明其作为诊断生物标志物的潜力,预后,指标和治疗目标。
方法:我们通过TIMER2.0进行了泛癌症分析,评估了SLC31A1在多种癌症类型中的表达。使用KM绘图仪进行生存分析。使用UALCAN和人蛋白图谱(HPA)数据库进行表达验证。在ULACAN和OncoDB的帮助下进行甲基化分析。使用cBioPortal数据库进行突变分析。通过TIMER2.0进行免疫浸润分析和通过Metascape进行基因富集分析,以深入了解SLC31A1在癌症中的潜在作用机制。最后,逆转录-定量聚合酶链反应(RT-qPCR)用于确认临床样品中的SLC31A1表达。
结果:在分析的癌症中,SLC31A1在整个乳腺癌(BRCA)中表现出显着的上调和与较差的总生存期(OS)的相关性,宫颈鳞状细胞癌(CESC),头颈部鳞状细胞癌(HNSC),和食管癌(ESCA)。突变和启动子甲基化分析进一步表明,低甲基化是BRCA中SLC31A1过表达的主要原因,CESC,HNSC,和ESCA。免疫浸润分析显示SLC31A1表达与CD8+T细胞的存在之间存在显著关联,CD4+T细胞,和肿瘤微环境中的巨噬细胞。基因富集分析为BRCA的潜在分子途径提供了有价值的见解,CESC,HNSC,和ESCA。此外,当使用临床样本通过RT-qPCR分析SLC31A1时,这个基因显示出有希望的诊断潜力,由高曲线下面积(AUC)值反映。
结论:我们的泛癌症研究强调了SLC31A1的上调及其与BRCA不良OS的相关性,CESC,HNSC,和ESCA。总之,这项研究的结果表明,SLC31A1可能是BRCA的潜在生物标志物和新的治疗靶点,CESC,HNSC,和ESCA。
OBJECTIVE: Cancer remains a global health challenge, necessitating the identification of novel biomarkers and therapeutic targets. Cuproptosis, a recently recognized form of cell death linked to copper metabolism, presents a promising avenue for anticancer strategies. We investigated the clinical significance of
SLC31A1, a key regulator of cuproptosis, in multiple cancer types, aiming to elucidate its potential as a diagnostic biomarker, prognostic, indicator and therapeutic target.
METHODS: We conducted a pan-cancer analysis through TIMER2.0, evaluating
SLC31A1 expression across multiple cancer types. Survival analysis was performed using KM plotter. Expression validation was carried out using UALCAN and Human Protein Atlas (HPA) databases. Methylation analysis was conducted with the help of ULACAN and OncoDB. Mutational analysis was performed using cBioPortal database. Immune infiltration analysis via the TIMER2.0 and gene enrichment analysis via the Metascape were performed to gain insights into the potential mechanisms underlying SLC31A1\'s role in cancer. Finally, Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to confirm SLC31A1 expression in clinical samples.
RESULTS: Out of analyzed cancer,
SLC31A1 exhibited significant up-regulation and correlation with worse overall survival (OS) across Breast Cancer (BRCA), Cervical Squamous Cell Carcinoma (CESC), Head and Neck Squamous Cell Carcinoma (HNSC), and Esophageal Carcinoma (ESCA). Mutational and promoter methylation analyses further revealed that hypomethylation is the major cause of SLC31A1 overexpression among BRCA, CESC, HNSC, and ESCA. Immune infiltration analysis showed significant associations between
SLC31A1 expression and the presence of CD8+ T cells, CD4+ T cells, and macrophages in the tumor microenvironment. Gene enrichment analysis provided valuable insights into potential molecular pathways in context to BRCA, CESC, HNSC, and ESCA. Furthermore, when SLC31A1 was analyzed using clinical samples through RT-qPCR, this gene showed promising diagnostic potential, reflected by high Area Under the Curve (AUC) values.
CONCLUSIONS: Our pan-cancer study highlights the up-regulation of SLC31A1 and its correlation with worse OS in BRCA, CESC, HNSC, and ESCA. In sum, outcomes of this study showed that
SLC31A1 could be a potential biomarker and novel therapeutic target of BRCA, CESC, HNSC, and ESCA.