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

Abstract

ObjectiveMany 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.MethodsTranscriptomic 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.ResultsWe 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.ConclusionWe constructed a novel necroptosis-related signature that predicts BLCA outcomes and performs satisfactorily in the immune landscape and chemotherapeutic responses.

Construction and experimental validation of a B cell-related gene signature to predict the prognosis and immunotherapeutic sensitivity in bladder cancer

“…The rapid development of genomic technologies and big-data analyses provided novel insights into the molecular mechanisms of BLCA. The analyses of the biomarkers from a particular aspect, such as pyroptosis [ 30 ], necroptosis [ 31 , 32 ], autophagy [ 33 , 34 ], tumor-infiltrating T cells and neutrophils [ 35 ], glycolysis [ 36 ], and ferroptosis [ 37 ], deepened our understandings of the underlying mechanisms and offered the possible therapeutic targets in BLCA. Similar to those excellent researches, our work also helped to uncover the novel molecular mechanisms in BLCA.…”

Qualification of Necroptosis-Related lncRNA to Forecast the Treatment Outcome, Immune Response, and Therapeutic Effect of Kidney Renal Clear Cell Carcinoma

“…In breast cancer, Xu et al, Chen et al, Xie et al, and Zhang et al studied the link between tumor microenvironment and NLR signatures [43][44][45][46], as well as miRNA signatures [47]. An axis linking an lncRNA with a microRNA and the target gene was shown in bladder cancer progression and metastasis [48,49]. A similar approach has been used to study laryngeal squamous cell carcinoma [50].…”