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 Centre, 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 tumours, underscoring its potential role in driving tumour 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 tumour 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, tumours 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-sulphur 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 tumour-suppressive functions in these cancers.

The authors acknowledge the lack of experimental validation as a limitation of the study and also recognise that data set heterogeneity, including variations in data processing and normalisation 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”.

Source: Compuscript Ltd