Abstract
BackgroundThere has been no report of prognostic signature based on immune-related genes (IRGs). This study aimed to develop an IRG-based prognostic signature that could stratify patients with bladder cancer (BLCA).MethodsRNA-seq data along with clinical information on BLCA were retrieved from the Cancer Genome Atlas (TCGA) and gene expression omnibus (GEO). Based on TCGA dataset, differentially expressed IRGs were identified via Wilcoxon test. Among these genes, prognostic IRGs were identified using univariate Cox regression analysis. Subsequently, we split TCGA dataset into the training (n = 284) and test datasets (n = 119). Based on the training dataset, we built a least absolute shrinkage and selection operator (LASSO) penalized Cox proportional hazards regression model with multiple prognostic IRGs. It was validated in the training dataset, test dataset, and external dataset GSE13507 (n = 165). Additionally, we accessed the six types of tumor-infiltrating immune cells from Tumor Immune Estimation Resource (TIMER) website and analyzed the difference between risk groups. Further, we constructed and validated a nomogram to tailor treatment for patients with BLCA.ResultsA set of 47 prognostic IRGs was identified. LASSO regression and identified seven BLCA-specific prognostic IRGs, i.e., RBP7, PDGFRA, AHNAK, OAS1, RAC3, EDNRA, and SH3BP2. We developed an IRG-based prognostic signature that stratify BLCA patients into two subgroups with statistically different survival outcomes [hazard ratio (HR) = 10, 95% confidence interval (CI) = 5.6–19, P < 0.001]. The ROC curve analysis showed acceptable discrimination with AUCs of 0.711, 0.754, and 0.772 at 1-, 3-, and 5-year follow-up respectively. The predictive performance was validated in the train set, test set, and external dataset GSE13507. Besides, the increased infiltration of CD4+ T cells, CD8+ T cells, macrophage, neutrophil, and dendritic cells in the high-risk group (as defined by the signature) indicated chronic inflammation may reduce the survival chances of BLCA patients. The nomogram demonstrated to be clinically-relevant and effective with accurate prediction and positive net benefit.ConclusionThe present immune-related signature can effectively classify BLCA patients into high-risk and low-risk groups in terms of survival rate, which may help select high-risk BLCA patients for more intensive treatment.
Highlights
Bladder cancer (BLCA) is the most common malignancy of the urinary system with high morbidity and mortality rates (Bray et al, 2018)
By accessing the Immunology Database and Analysis Portal (IMMPORT) (Bhattacharya et al, 2014) website, we retrieved a latest list of immune‐related genes, out of which we identified BLCA-specific immune‐related genes (IRGs) after matching the differentially expressed genes (DEGs)
The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis (Figure 1) indicated that the genes were mainly involved in PI3K−Akt and MAPK signaling pathway, which are pivotal in the regulation of immune responses (Liu et al, 2007; Weichhart and Säemann, 2008)
Summary
Bladder cancer (BLCA) is the most common malignancy of the urinary system with high morbidity and mortality rates (Bray et al, 2018). 25% of BLCA patients are diagnosed with muscle-invasive or metastatic disease during the early stages of prognosis (Akbani et al, 2017). Patients with nonmuscle-invasive BLCA continue to suffer from the high progression rates (Cambier et al, 2016; Chen et al, 2019). Once the tumor progresses to locally advanced or metastatic stage, standard treatment for BLCA with combination chemotherapy are insufficient with low response and survival rates (Von et al, 2000; Maase et al, 2006). Most BLCA patients do not adequately respond to PD-1 or PD-L1-targeted therapy; and it is imperative to develop prognostic biomarkers to closely monitor progression and shed light on treatment stratification. This study aimed to develop an IRG-based prognostic signature that could stratify patients with bladder cancer (BLCA)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
