Identification of CISD1 as a Prognostic Biomarker for Breast Cancer

Xiao Liu,1 Qianqian Cui1,2 1Department of Breast Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, 110042, People’s Republic of China; 2Department of Breast Surgery, Altaira Nursing Service, Campbelltown, NSW, SA 5074, AustraliaCorrespondence: Xiao Liu, Email liuxiao@cancerhosp-ln-cmu.comBackground: Although CISD1 (CDGSH iron sulfur domain 1) is upregulated in many cancer types, the potential role of CISD1 in breast cancer is still unclear. The purpose of this study was to investigate its clinical significance in breast cancer.Methods: We obtained 1109 breast cancer samples and 113 normal samples from The Cancer Genome Atlas (TCGA) and GTEx databases to demonstrate the relationship between CISD1 expression and pancancer characteristics. We analysed the relationship between CISD1 and breast cancer using the t-test and the chi-square test to evaluate the expression level of CISD1 and its clinical significance in breast cancer. The prognostic value of CISD1 in breast cancer was determined by Kaplan‒Meier and Cox regression analyses. The biological pathways were screened by gene set analysis and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and single-sample gene set enrichment analysis (ssGSEA), of which the correlation between the level of immune infiltration and the expression of CISD1 in breast cancer was then analysed. Finally, we verified the conclusion by qPCR, immunohistochemistry, and CCK8.Results: CISD1 is highly expressed in breast cancer patients. In addition, we verified a higher expression of CISD1 expressed in the BRCA (breast cancer) cell line, whereas CISD1 has a high diagnostic value, with an AUC of 0.718. Kaplan‒Meier survival and Cox regression analyses showed that high expression of CISD1 was independently associated with adverse clinical outcomes. In turn, GO and KEGG analyses showed that most genes were related to rRNA metabolic process, rRNA processing. Moreover, PCR and immunohistochemistry showed that CISD1 in breast cancer tissues was upregulated significantly, with CCK8 results showing that the proliferation of breast cancer cells decreased after CISD1 knockout.Conclusion: A high level of CISD1 is associated with poor prognosis and immune infiltration in breast cancer.Keywords: breast cancer, cancer prognosis, immunotherapy, bioinformatics, CISD