Mi Jiaoping, Luo Juncong, Zeng Huanwen, Zhang Hongyu, Jamil Muhammad, Abdel-Maksoud Mostafa A, Zakri Adel M, Alfuraydi Akram A, Zhang Ning, Xiao Mei
Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital, Sun Yat-sen University Guangzhou 510080, Guangdong, PR China.
Department of Otolaryngology Head and Neck Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University Zhuhai 519000, Guangdong, PR China.
Am J Transl Res. 2023 Oct 15;15(10):6026-6041. eCollection 2023.
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.
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.
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.
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.
癌症仍然是一项全球性的健康挑战，因此需要鉴定新的生物标志物和治疗靶点。铜死亡是一种最近被认识到的与铜代谢相关的细胞死亡形式，为抗癌策略提供了一条有前景的途径。我们研究了铜死亡关键调节因子SLC31A1在多种癌症类型中的临床意义，旨在阐明其作为诊断生物标志物、预后指标和治疗靶点的潜力。
我们通过TIMER2.0进行了泛癌分析，评估了SLC31A1在多种癌症类型中的表达。使用KM plotter进行生存分析。使用UALCAN和人类蛋白质图谱（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，并通过Metascape进行基因富集分析，以深入了解SLC31A1在癌症中作用的潜在机制。最后，采用逆转录定量聚合酶链反应（RT-qPCR）来确认临床样本中SLC31A1的表达。
在分析的癌症中，SLC31A1在乳腺癌（BRCA）、宫颈鳞状细胞癌（CESC）、头颈部鳞状细胞癌（HNSC）和食管癌（ESCA）中表现出显著上调，并且与较差的总生存期（OS）相关。突变和启动子甲基化分析进一步表明，低甲基化是BRCA、CESC、HNSC和ESCA中SLC31A1过表达的主要原因。免疫浸润分析显示SLC31A1表达与肿瘤微环境中CD8 + T细胞、CD4 + T细胞和巨噬细胞的存在之间存在显著关联。基因富集分析为与BRCA、CESC、HNSC和ESCA相关的潜在分子途径提供了有价值的见解。此外，当通过RT-qPCR使用临床样本分析SLC31A1时，该基因显示出有前景的诊断潜力，这通过高曲线下面积（AUC）值反映出来。
我们的泛癌研究突出了SLC31A1在BRCA、CESC、HNSC和ESCA中的上调及其与较差OS的相关性。总之，本研究结果表明SLC31A1可能是BRCA、CESC、HNSC和ESCA的潜在生物标志物和新型治疗靶点。
