Li Caiyue, Liang Zhipin, Vontz Gabrielle, Kent Connor, Ma Wenbo, Liu Lei, Dahal Riya, Zabaleta Jovanny, Cai Guoshuai, Zhou Jia, Ding Huangen, Shen Qiang
Department of Interdisciplinary Oncology, School of Medicine, LSU LCMC Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Genetics Graduate Program, School of Medicine, LSU LCMC Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Genes Dis. 2025 May 8;12(6):101677. doi: 10.1016/j.gendis.2025.101677. eCollection 2025 Nov.
CISD1, an outer mitochondrial membrane iron-sulfur cluster protein, regulates intracellular iron levels, oxidative stress, and mitochondrial dynamics, playing critical roles in cellular bioenergetics and redox homeostasis. Although CISD1 has been identified as a prognostic biomarker in specific cancers, its broader implications in tumorigenesis, cancer progression, and immunotherapy remain unclear. Given the heterogeneity of cancer and the need for robust biomarkers across cancers, this study conducts the first comprehensive pan-cancer analysis of CISD1 by evaluating its roles in cancer and treatment. We obtained and analyzed data from databases including TCGA, GTEx, THPA, GEPIA2.0, SangerBox, cBioPortal, TIMER2.0, CAMOIP, DAVID, SRPLOT, and TISIDB. Our findings reveal significant alterations in CISD1 expression at both transcriptional and translational levels, as well as gene mutations across multiple cancers, indicating its potential as a diagnostic biomarker and its involvement in cancer development and progression. CISD1 dysregulation is linked to poor clinical outcomes, as shown through its impact on patient prognosis. GO and KEGG analyses show that CISD1 plays critical roles in cellular bioenergetics. Notably, CISD1 expression is significantly correlated with tumor stemness indices, tumor mutation burden, microsatellite instability, and immune checkpoint proteins in multiple cancers, and altered CISD1 levels are also observed in patients responding to immunotherapy, further supporting its role not only in prognosis but also as a key predictor in immunotherapy responses and outcomes. Our findings demonstrate CISD1 as a reliable and promising diagnostic, prognostic, and immunotherapeutic biomarker for multiple cancers, emphasizing its crucial role in cancer biology and potential to guide personalized cancer therapies.
CISD1是一种线粒体外膜铁硫簇蛋白，可调节细胞内铁水平、氧化应激和线粒体动力学，在细胞生物能量学和氧化还原稳态中发挥关键作用。尽管CISD1已被确定为特定癌症的预后生物标志物，但其在肿瘤发生、癌症进展和免疫治疗中的更广泛意义仍不清楚。鉴于癌症的异质性以及对跨癌症的强大生物标志物的需求，本研究通过评估CISD1在癌症和治疗中的作用，首次对其进行了全面的泛癌分析。我们从包括TCGA、GTEx、THPA、GEPIA2.0、SangerBox、cBioPortal、TIMER2.0、CAMOIP、DAVID、SRPLOT和TISIDB在内的数据库中获取并分析了数据。我们的研究结果显示，CISD1在转录和翻译水平上的表达均有显著改变，并且在多种癌症中存在基因突变，表明其作为诊断生物标志物的潜力以及其参与癌症发展和进展。CISD1失调与不良临床结果相关，这通过其对患者预后的影响得以体现。基因本体（GO）和京都基因与基因组百科全书（KEGG）分析表明，CISD1在细胞生物能量学中起关键作用。值得注意的是，CISD1表达与多种癌症中的肿瘤干性指数、肿瘤突变负担、微卫星不稳定性和免疫检查点蛋白显著相关，并且在接受免疫治疗的患者中也观察到CISD1水平的改变，这进一步支持了其不仅在预后方面，而且在免疫治疗反应和结果的关键预测方面的作用。我们的研究结果表明，CISD1是一种可靠且有前景的用于多种癌症的诊断、预后和免疫治疗生物标志物，强调了其在癌症生物学中的关键作用以及指导个性化癌症治疗的潜力。
