An Oxidative Stress-Related Genes Signature for Predicting Survival in Bladder Cancer: Based on TCGA Database and Bioinformatics

Abstract

Background Oxidative stress (OS) responses have been linked to oncogenesis and tumor progression and have recently been regarded as a potential strategy for tumor therapy. However, OS-related therapeutic targets have not been identified to date in the bladder cancer (BC). Methods The mRNA expression and clinical data of BC were downloaded from the public database. Prognostic risk score signature was constructed using LASSO Cox regression analysis. External validation was performed in GSE15307 cohort. ESTIMATE, CIBERSORT, and ssGSEA algorithm were used to analyze immune cell infiltration and immune microenvironment. Next, functional enrichment analysis was performed to elucidate the mechanism underlying the signature. Additionally, we performed a nomogram to forecast the survival rate of individual BC patients. Results An OS-related genes (OSRGs) signature was constructed. Overall survival was lower in the high-risk group than in the low-risk group, according to survival analyses. The area under the curve (AUC) of ROC curves further validated the prognostic signature’s strong prediction performance in these two cohorts. The risk score was verified as an independent risk factor for BC by independent prognostic analysis. Moreover, as compared to TNM stage alone, a nomogram that integrated the risk score with TNM stage showed a much superior predictive value. Immune infiltration and tumor microenvironment studies indicated that immune cells and functions may play a significant role in carcinogenesis and development. The levels of expression of prognostic genes were shown to be substantially linked with drug sensitivity. Conclusion We developed a novel OSRGs signature for predicting overall survival and impacting the immune status in patients with BC. New nomogram can help clinicians predict the survival rate of BC patients. These findings shed new light on the potential usage of OSRGs signature in BC patients.

Integrated analysis identifies oxidative stress-related lncRNAs associated with progression and prognosis in colorectal cancer

“…An increasing number of studies have confirmed that oxidative stress plays a crucial role in carcinogenesis and tumor treatment [ 25 – 27 ]. The construction of prognostic models based on public databases provides a more comprehensive clinical genetic prognostic value, and oxidative stress-based prognostic models are becoming a research hotspot for predicting the survival prognosis of different cancers [ 28 – 30 ]. However, the predictive value of oxidative stress-based prognostic models for the prognosis of CRC patients is still unknown and deserves further investigation.…”

Establishment and external verification of an oxidative stress-related gene signature to predict clinical outcomes and therapeutic responses of colorectal cancer

“…Oxidative stress-related signatures have been established in acute myeloid leukemia ( Dong et al, 2021 ), melanoma ( Yang et al, 2021 ), clear-cell renal cell carcinoma ( Wu Y. et al, 2021a ), gastric cancer ( Wu Z. et al, 2021b ), head and neck squamous cell carcinoma ( Wang and Zhou, 2021 ), glioma ( Lu et al, 2021 ), and bladder cancer ( Zhang et al, 2022 ). Alterations in redox status accompanied by increased production of ROS have been implicated in CRC ( Lee et al, 2021 ).…”

Oxidative Stress Markers in Urine and Serum of Patients with Bladder Cancer

“…ROS experimentally induce a long interspersed expression of nuclear element-1 encoded protein expression and promote migration in bladder cancer cells [35]. The use of oxidative stress biomarkers and the oxidative stress-related gene signature to guide treatment decisions along with the development of immunotherapy may benefit the patient [36]. Furthermore, the increase in ROS may be associated with impairment in the microenvironment of cancer cells [37].…”