Despite significant advancements in medicine, cancer remains a major health challenge and the leading cause of mortality worldwide, highlighting the urgent need for continued research to identify robust biomarkers for the early detection, prognosis, and treatment across multiple cancer types.

In a recent study, published in the Genes & Diseases journal, researchers at Louisiana State University Health Sciences Center, Tulane University, University of Florida, University of Texas Medical Branch, and Louisiana State University, provide the first comprehensive pan-cancer bioinformatics analysis determining the functions of CISD1 in multiple cancers using public patient databases, and demonstrate its potential as a multi-faceted biomarker in various cancers.

Data obtained from TCGA, GTEx, THPA, GEPIA2.0, SangerBox, cBioPortal, TIMER2.0, CAMOIP, DAVID, SRPLOT, and TISIDB databases showed significant alterations in the expression of CISD1 at both the transcriptional and translational levels in various cancers. Mutations in the CISD1 gene within the zf-CDGSH domain, especially at the A69S/V (a hotspot mutation site), in multiple cancers highlight its role in cancer initiation and progression, and its potential as a diagnostic biomarker.

High CISD1 expression was associated with poor clinical outcomes, including low survival and high mortality risk. A positive correlation between CISD1 and stemness indices in multiple cancers suggests that CISD1 promotes or maintains stem cell-like properties in cancer cells, and may serve as an indicator of stem-cell-enriched tumors, underscoring its potential role in driving tumor aggressiveness and therapeutic resistance. High expression of CISD1 along with increased stemness levels was associated with poor prognosis. Additionally, CISD1 plays a critical role in cellular bioenergetics, significantly correlating with tumor mutation burden and microsatellite instability, and ultimately poor prognosis in multiple cancers. These findings reinforce its feasibility as a potential prognostic marker.

Moreover, CISD1 expression was altered in patients undergoing immunotherapy; specifically, tumors with high CISD1 expression showed increased levels of immune checkpoint proteins, which serve as targets for immune checkpoint blockade. Since elevated immune checkpoints are considered effective immunotherapeutic targets, overexpression of CISD1 may serve as a reliable biomarker for immunotherapy, further solidifying its role as not only a diagnostic and prognostic biomarker but also as a key predictor of immunotherapy outcomes.

This study not only establishes CISD1 as a multi-faceted biomarker but also highlights its potential as a therapeutic target in multiple cancers. Therapeutic strategies targeting CISD1's iron-sulfur cluster or modulating its protein expression may hold great potential for improving cancer outcomes. Furthermore, CISD1 exhibits a dual role in cancer. While its expression is upregulated in most cancers, the expression of CISD1 was down-regulated in six types of cancer, suggesting that CISD1 may play tumor-suppressive functions in these cancers.

The authors acknowledge the lack of experimental validation as a limitation of the study and also recognize that data set heterogeneity, including variations in data processing and normalization across platforms, could have introduced unfavored biases affecting the findings of this study. However, this “systematic pan-cancer analysis lays a strong foundation for further exploring the biological functions of CISD1 in cancers”.

In conclusion, this comprehensive pan-cancer bioinformatics analysis on the role of the CISD1 gene in different aspects of tumorigenesis reveals that CISD1 could serve as a “reliable and promising diagnostic, prognostic, and immunotherapeutic biomarker in multiple cancers”.

Reference

Title of the original paper: Exploring CISD1 as a multifaceted biomarker in cancer: Implications for diagnosis, prognosis, and immunotherapeutic response

Journal: Genes & Diseases

Genes & Diseases is a journal for molecular and translational medicine. The journal primarily focuses on publishing investigations on the molecular bases and experimental therapeutics of human diseases. Publication formats include full length research article, review article, short communication, correspondence, perspectives, commentary, views on news, and research watch.

DOI: https://doi.org/10.1016/j.gendis.2025.101677

Funding Information:

Louisiana State University Health Sciences Center (LSUHSC) Startup funds (New Orleans, Louisiana, USA)
Louisiana State University (LSU) Interinstitutional Cancer Research Funding Initiative (Louisiana, USA) (CCRI)
Louisiana Cancer Research Center (LCRC) Strategic Investment in Translational Research Awards (Louisiana, USA)
John D. Stobo, M.D. Distinguished Chair Endowment (USA)
Edith & Robert Zinn Chair Endowment in Drug Discovery (USA)

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Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.

Scopus CiteScore: 8.4 | Impact Factor: 9.4

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