A novel ferroptosis-related gene signature associated with cell cycle for prognosis prediction in patients with clear cell renal cell carcinoma

• Published in: BMC cancer Vol. 22; no. 1; pp. 1 - 11
• Main Authors: Chen, Siteng, Zhang, Encheng, Guo, Tuanjie, Shao, Jialiang, Wang, Tao, Zhang, Ning, Wang, Xiang, Zheng, Junhua
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 03-01-2022; BioMed Central; BMC
• Subjects: Accuracy; Aged; Apoptosis; Biomarkers, Tumor - genetics; Carcinoma, Renal cell; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - mortality; Cell culture; Cell cycle; Cell Cycle - genetics; Cell death; Clear cell renal cell carcinoma; Clear cell-type renal cell carcinoma; Cohort Studies; Correlation analysis; Cytokinesis; Female; Ferroptosis; Ferroptosis - genetics; Gene expression; Gene Expression Regulation, Neoplastic; Genetic aspects; Genetic Testing - statistics & numerical data; Health aspects; Humans; Kidney cancer; Kidney Neoplasms - genetics; Kidney Neoplasms - mortality; Male; Medical prognosis; Metastasis; Middle Aged; Neoplasm Staging; Nomogram; Nomograms; Nuclear division; Patient outcomes; Patients; Performance evaluation; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Regression analysis; Risk factors; Statistical analysis; Survival Analysis; Tumors; Variance analysis; China; Ferroptosis; Clear cell renal cell carcinoma; Prognosis; Nomogram; Cell cycle
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-021-09033-7

It is of great urgency to explore useful prognostic markers for patients with clear cell renal cell carcinoma (ccRCC). Prognostic models based on ferroptosis-related gene (FRG) in ccRCC is poorly reported for now.
Comprehensive analysis of 22 FRGs were performed in 629 ccRCC samples from two independent patient cohorts. We carried out least absolute shrinkage and selection operator analysis to screen out prognosis-related FRGs and constructed prognosis model for patients with ccRCC. Weighted gene co-expression network analysis was also carried out for potential functional enrichment analysis.
Based on the TCGA cohort, a total of 11 prognosis-associated FRGs were selected for the construction of the prognosis model. Significantly differential overall survival (hazard ratio = 3.61, 95% CI: 2.68-4.87, p < 0.0001) was observed between patients with high and low FRG score in the TCGA cohort, which was further verified in the CPTAC cohort with hazard ratio value of 5.13 (95% CI: 1.65-15.90, p = 0.019). Subgroup survival analysis revealed that our FRG score could significantly distinguish patients with high survival risk among different tumor stages and different tumor grades. Functional enrichment analysis illustrated that the process of cell cycle, including cell cycle-mitotic pathway, cytokinesis pathway and nuclear division pathway, might be involved in the regulation of ccRCC through ferroptosis.
We developed and verified a FRG signature for the prognosis prediction of patients with ccRCC, which could act as a risk factor and help to update the tumor staging system when integrated with clinicopathological characteristics. Cell cycle-related pathways might be involved in the regulation of ccRCC through ferroptosis.