A Necroptosis-Related lncRNA to Develop a Signature to Predict the Outcome, Immune Landscape, and Chemotherapeutic Responses in Bladder Urothelial Carcinoma

Jian Hou; Zhenquan Lu; Runan Dong; Guoqing Wu; Haibo Nie; Guang Yang; Cheng Tang; Genyi Qu; Yong Xu

doi:10.3389/fonc.2022.928204

A Necroptosis-Related lncRNA to Develop a Signature to Predict the Outcome, Immune Landscape, and Chemotherapeutic Responses in Bladder Urothelial Carcinoma

Front Oncol. 2022 Jun 24:12:928204. doi: 10.3389/fonc.2022.928204. eCollection 2022.

Authors

Jian Hou^{1

2}, Zhenquan Lu², Runan Dong², Guoqing Wu², Haibo Nie¹, Guang Yang¹, Cheng Tang¹, Genyi Qu¹, Yong Xu¹

Affiliations

¹ Department of Urology, Zhuzhou Central Hospital, Zhuzhou, China.
² Division of Urology, Department of Surgery, The University of Hongkong-ShenZhen Hospital, ShenZhen, China.

Abstract

Objective: Many studies have drawn their attention to the immunotherapy of bladder urothelial carcinoma in terms of immunologic mechanisms of human body. These include immunogenicity of the tumor cells and involvement of long non-coding RNA (lncRNA). We constructed a necroptosis-related long noncoding RNA (nrlncRNA) risk factor model to predict BLCA outcomes and calculate correlations with chemosensitivity and immune infiltration.

Methods: Transcriptomic data from BLCA specimens were accessed from The Cancer Genome Atlas, and nrlncRNAs were identified by performing co-expression analysis. Univariate analysis was performed to identify differentially expressed nrlncRNA pairs. We constructed least absolute contraction and selector operation regression models and drew receiver operating characteristic curves for 1-, 3-, and 5-year survival rates. Akaike information criterion (AIC) values for survival over 1 year were determined as cutoff values in high- and low-risk subgroups. We reassessed the differences between subgroups in terms of survival, clinicopathological characteristics, chemotherapy efficacy, tumor-infiltrating immune cells, and markers of immunosuppression.

Results: We identified a total of 260 necroptosis-related lncRNA pairs, of which we incorporated 13 into the prognostic model. Areas under the curve of 1-, 3-, and 5- year survival time were 0.763, 0.836, and 0.842, respectively. We confirmed the excellent predictive performance of the risk model. Based on AIC values, we confirmed that the high-risk group was susceptible to unfavorable outcomes. The risk scores correlated with survival were age, clinical stage, grade, and tumor node metastases. The risk model was an independent predictor and demonstrated higher predictive power. The risk model can also be utilized to determine immune cell infiltration status, expression levels of immune checkpoint genes, and the sensitivity to cisplatin, doxorubicin, and methotrexate.

Conclusion: We constructed a novel necroptosis-related signature that predicts BLCA outcomes and performs satisfactorily in the immune landscape and chemotherapeutic responses.

Keywords: bladder urothelial carcinoma; chemotherapeutic response; immune checkpoint; lncRNA signature; necroptosis-related; outcomes.