Abstract
Purpose This study aimed to establish a nomogram to predict the overall survival (OS) of patients with bladder cancer (BC) by ferroptosis-related long noncoding RNAs (FRlncRNAs) signature. Methods We obtained FRlncRNAs expression profiles and clinical data of patients with BC from the Cancer Genome Atlas database. The patients were divided into the training set, testing set, and overall set. Lasso regression and multivariate Cox regression were used to establish the FRlncRNAs signature, the prognosis of each group was compared by Kaplan–Meier (K-M) analysis, and the receiver operating characteristic (ROC) curve evaluated the accuracy of the model. The Gene Set Enrichment Analysis (GSEA) was used for the visualization of the functional enrichment for FRlncRNAs. The databases of GEPIA and K-M Plotter were used for subsequent functional analysis of major FRlncRNAs. Results Thirteen prognostic FRlncRNAs (LINC00942, MAFG-DT, AL049840.3, AL136084.3, OCIAD1-AS1, AC062017.1, AC008074.2, AC018653.3, AL031775.1, USP30-AS1, LINC01767, AC132807.2, and AL354919.2) were identified to be significantly different, constituting an FRlncRNAs signature. Patients with BC were divided into low-risk group and high-risk group by this signature in the training, testing, and overall sets. K-M analysis showed that the prognosis of patients in the high-risk group was poor and the difference in the subgroup analyses was statistically significant. ROC analysis revealed that the predictive ability of the model was more accurate than traditional assessment methods. A risk score based on FRlncRNAs signature was an independent prognostic factor for the patients with BC (HR = 1.388, 95%CI = 1.228–1.568, P < 0.001). Combining the FRlncRNAs signature and clinicopathological factors, a predictive nomogram was constructed. The nomogram can accurately predict the overall survival of patients and had high clinical practicability. The GSEA analysis showed that the primary pathways were WNT, MAPK, and cell-matrix adhesion signaling pathways. The major FRlncRNAs (MAFG-DT) were associated with poor prognosis in the GEPIA and K-M Plotter database. Conclusion Thirteen prognostic FRlncRNAs and their nomogram were accurate tools for predicting the OS of BC, which might be molecular biomarkers and therapeutic targets.
Highlights
Bladder cancer (BC) is one of the most common cancers worldwide, with nearly 430,000 newly diagnosed patients each year [1]
By univariate Cox regression, we screened a total of 177 FRlncRNAs with prognostic value for patients with BC (P < 0.05). en, we identified 29 FRlncRNAs by lasso regression (Figures 2(a) and 2(b) and Table S1)
To access the sensitivity and stability of this signature, the patients in the training set were divided into low-risk group (99 cases) and high-risk group (98 cases) based on the median of risk scores. e K-M curve showed a shorter overall survival (OS) in the high-risk group compared with the low-risk group (P < 0.001) (Figure 2(c)). en, the study used receiver operating characteristic (ROC) curve to assess the accuracy of the signature and found an area under the curve (AUC) value of 0.776 in the training set (Figure 2(d)). e heatmap showed a significant difference in the expression of 13 FRlncRNAs between the high-risk group and the low-risk group (Figure 2(e))
Summary
Bladder cancer (BC) is one of the most common cancers worldwide, with nearly 430,000 newly diagnosed patients each year [1]. Unlike other tumors with a single direction of progression, BC is divided into two types, including nonmuscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) [3]. NMIBC can be treated by transurethral resection, about 20% of patients with NMIBC progress to MIBC within 5 years, followed by lymphatic metastasis and distant organ metastasis [6, 7]. With the development of molecular mechanism research, ferroptosis has been proved to be involved in a variety of important pathophysiological processes, mainly including the occurrence of cancer and the formation of ischemia-reperfusion injury and neurodegenerative diseases [10]. An increasing number of studies support the involvement of ferroptosis in the pathophysiology of BC development and progression [12, 13]
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