A Novel Ferroptosis-Related Gene Model for Overall Survival Predictions of Bladder Urothelial Carcinoma Patients

一种用于预测膀胱尿路上皮癌患者总体生存率的新型铁死亡相关基因模型

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作者:Min Zhang, Xin Zhang, Minghang Yu, Wei Zhang, Di Zhang, Song Zeng, Xi Wang, Xiaopeng Hu

Conclusions

This study defined a novel prognostic model of seven ferroptosis-related genes, which proved to be independently associated with the OS of BLCA. A nomogram method was developed for the purpose of providing further insight into the accurate predictions of BLCA prognoses.

Discussion

A 7-gene FRPM was constructed in this research investigation in order to stratify the patients into two groups according to their risk scores. The results of this study's survival analysis and time-dependent receiver operating characteristic (ROC) analysis demonstrated that the model had achieved a stable performance level. This multivariate Cox regression results revealed that the FRPM was an independent prognostic predictor for the OS of BLCA patients and the results were displayed using a nomogram. In addition, the ROC analysis, concordance index (C-index), calibration plots, and decision curve analysis (DCA) curves further indicated that this study's nomogram method enabled valuable prediction results. The functional enrichment analysis results suggested that the DEGs between the high- and low-risk groups played vital roles in the progression of the ferroptosis. Also, the ssGSEA indicated that the immune status was different between the two groups. This study found that the RT-qPCR results had confirmed the differential expressions of DEGs in the tissue samples, and the CCK-8 assay and scratch assay results confirmed the promoting effects of SCD on the proliferation and migration of tumor cells. Conclusions: This study defined a novel prognostic model of seven ferroptosis-related genes, which proved to be independently associated with the OS of BLCA. A nomogram method was developed for the purpose of providing further insight into the accurate predictions of BLCA prognoses.

Methods

In the current study, expression profiles of bladder cancer (BLCA) specimens were obtained from The Cancer Genome Atlas (TCGA) RNA-Seq database. Ferroptosis-related genes were downloaded from the FerrDb website. The ferroptosis-related differentially expressed genes (DEGs) which were related to overall survival (OS) were first identified. The least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression methods were utilized to develop a ferroptosis-related prognostic model (FRPM). In addition, a nomogram model based on FRPM and clinicopathological features was successfully constructed and validated. In addition, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and single-sample gene set enrichment analysis (ssGSEA) methods were utilized in this study in order to compare the DEGs between the high-risk and low-risk groups. This study also adopted RT-qPCR, CCK-8 assay, and scratch assay methods to perform experimental verification processes.

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