Overexpression of CISD1 Predicts Worse Survival in Hepatocarcinoma Patients

Abstract

Background. Ferroptosis plays a vital role in hepatocellular carcinoma (HCC). CISD1 is known to regulate ferroptosis negatively. However, the correlations of CISD1 to prognosis in HCC and its potential mechanism remain unclear. Aim. To investigate the expression level and prognostic value of CISD1 in HCC. Methods. Gene expression and clinical data for 33 cancer types in TCGA were downloaded from the UCSC Xena platform. Pan-cancer analysis was performed to determine the expression profile and prognostic value of CISD1 in human cancers. GEO datasets and Human Protein Atlas (HPA) were used to verify the mRNA and protein expression levels. The influence of CISD1 on clinical prognosis in HCC was evaluated using a Kaplan-Meier plotter. The PPI network was constructed using the STRING database and Cytoscape. GO and KEGG pathways were constructed using the “clusterProfiler” R package with the FDR cutoff of 0.05. The methylation at the CISD1 promoter was detected using UALCAN and GEO datasets. The correlations between CISD1 and HCC immune infiltrates were investigated via TIMER. Results. Pan-cancer analysis of TCGA data showed that CISD1 is differentially expressed in multiple tumors. Data of gene expression microarrays reveal that the mRNA expression of CISD1 is higher in HCC than that in normal tissue. The protein level of CISD1, validated by the Human Protein Atlas (HPA) database, was upregulated consistently with mRNA levels in HCC samples. High CISD1 expression was associated with better overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and progression-free survival (PFS) in LGG, but with poorer OS, DFS, DSS, and PFS in LIHC. Protein-protein interaction (PPI) analysis and GO/KEGG analysis showed that the PPI network and GO term of CISD1 were mainly associated with energy and iron metabolism. Promoter hypomethylation correlated with overexpression of CISD1. CISD1 expression was positively correlated with infiltrating levels of CD8+ T cells, macrophages, neutrophils, and dendritic cells (DCs) in HCC. Conclusions. These findings suggest that hypomethylation of the CISD1 promoter increases its expression in HCC. CISD1 is associated with prognosis and immune infiltrating levels of CD8+ T cells, macrophages, neutrophils, and DCs in HCC patients. These findings suggest that CISD1 can be used as a prognostic biomarker for determining prognosis in HCC.

GMRC: Gene Median Ratio Clustering Algorithm to Rank Clusters and Identify Driver Genes in Intrahepatic Cholangiocarcinoma

“…TUBA1B gene is overexpressed by 132% in the proliferation disease patients and is a potential biomarker in Wills Tumor (Xu et al 2020), also known as nephroblastoma in pediatric patients. While being a potential biomarker in children’s kidney cancer, it is a potential biomarker in Hepatocellular Carcinoma, the same as CISD1 (Lu et al 2022). CISD1 is overexpressed by 115% in our dataset in proliferation and is known to regulate ferroptosis negatively.…”

Development and validation of a combined hypoxia and ferroptosis prognostic signature for breast cancer

“…TPD52 is an oncogene and closely associated with prostate, breast cancer, and other cancers (102)(103)(104), which was consistent with our results. CISD1 reduces ferroptosis via iron-sulfur cluster biogenesis and was identified as prognostic ferroptosis-related genes in bladder cancer, lung cancer, and hepatocellular carcinoma (53,105,106). Although these researches provided some evidence to demonstrate its relation with tumor disease, its function in breast cancer has not been investigated yet.…”

Identification and Validation of Ferroptosis-Related DNA Methylation Signature for Predicting the Prognosis and Guiding the Treatment in Cutaneous Melanoma

“…CISD1 , a negative regulator of autophagy, was differentially expressed in a variety of tumors and correlated with OS [ 36 , 37 ]. Meanwhile, CISD1 can be served as a prognostic biomarker in patients with hepatocellular carcinoma [ 38 ]. DUOX1 is a new target for macrophage reprogramming, and is involved in the redox regulation of EGFR signaling; ATP-mediated DUOX1 activation led to the activation of the NF-kappaB pathway and production of IL-8 [ 39 , 40 , 41 ].…”