泛癌分析表明铜转运蛋白是很有前景的潜在靶点。

Pan-cancer analysis reveals copper transporters as promising potential targets.

作者信息

Li Yueqin, Yu Zhen

机构信息

Institute of Integrative Chinese Medicine, Department of Integrated Chinese Medicine, Xiangya Hospital, Central South University, Changsha, China.

NATCM Key Laboratory of TCM Gan, Xiangya Hospital, Central South University, Changsha, China.

出版信息

Heliyon. 2024 Aug 27;10(17):e37007. doi: 10.1016/j.heliyon.2024.e37007. eCollection 2024 Sep 15.

DOI:10.1016/j.heliyon.2024.e37007

PMID:39281483

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11402228/

Abstract

BACKGROUND

Copper transport proteins () regulate copper levels in the body and may be involved in tumor development. However, their comprehensive expression and function across various cancers remain unclear.

METHODS

The expressions of copper transporters in 33 tumors and normal tissues were analyzed using TCGA, GTEx, CCLE, ULCAN, and HPA databases. Cox regression assessed their impact on patient survival. Gene alterations were explored using cBioPortal. Spearman correlation tests were performed to investigate the associations between copper transporters and tumor mutation burden (TMB), microsatellite instability (MSI), and infiltration of immune cells. Gene functions were analyzed using STRING and GeneMANIA databases. Drug sensitivity was assessed using GSCALite database. expression in lung squamous cell carcinoma (LUSC) was validated by immunohistochemical staining.

RESULTS

Copper transporters exhibited variable expression patterns across various cancer types, indicating their potential dual role as either oncogenes or tumor suppressor genes, depending on the cancer type. Significant associations were found between these transporters and tumor stage, as well as prognosis in most tumors studied. Pathway analysis identified links between copper transporters and tumor-related pathways like apoptosis and RAS/MAPK. Copy number variation (CNV) analysis revealed varying degrees of gene amplification and deletion of copper transporters in most tumors. Copper transporters exhibited strong correlations with immune features, including TMB, MSI, and immune-infiltrating cells, suggesting their potential role in guiding immunotherapy. They were also associated with sensitivity to various chemotherapeutic and immunotherapeutic drugs. Immunohistochemical tests validated the correlation between elevated level and worse progression-free survival (PFS) in LUSC.

CONCLUSION

Copper transporters may serve as potential tumor markers and therapeutic targets.

摘要

背景

铜转运蛋白可调节体内铜水平，并可能参与肿瘤发展。然而，它们在各种癌症中的综合表达和功能仍不清楚。

方法

使用TCGA、GTEx、CCLE、ULCAN和HPA数据库分析33种肿瘤和正常组织中铜转运蛋白的表达。Cox回归评估它们对患者生存的影响。使用cBioPortal探索基因改变。进行Spearman相关性测试以研究铜转运蛋白与肿瘤突变负担（TMB）、微卫星不稳定性（MSI）和免疫细胞浸润之间的关联。使用STRING和GeneMANIA数据库分析基因功能。使用GSCALite数据库评估药物敏感性。通过免疫组织化学染色验证肺鳞状细胞癌（LUSC）中的表达。

结果

铜转运蛋白在各种癌症类型中表现出可变的表达模式，表明它们根据癌症类型可能作为癌基因或肿瘤抑制基因发挥潜在的双重作用。在这些转运蛋白与肿瘤分期以及大多数研究肿瘤的预后之间发现了显著关联。通路分析确定了铜转运蛋白与凋亡和RAS/MAPK等肿瘤相关通路之间的联系。拷贝数变异（CNV）分析显示大多数肿瘤中铜转运蛋白存在不同程度的基因扩增和缺失。铜转运蛋白与免疫特征（包括TMB、MSI和免疫浸润细胞）表现出强相关性，表明它们在指导免疫治疗中的潜在作用。它们还与对各种化疗和免疫治疗药物的敏感性相关。免疫组织化学测试验证了LUSC中水平升高与无进展生存期（PFS）较差之间的相关性。