Abstract
Background In recent years, immune-associated genes (IAGs) have been documented as having critical roles in the occurrence and progression of muscle-invasive bladder cancer (MIBC). Novel immune-related biomarkers and a robust prognostic signature for MIBC patients are still limited. The study is aimed at developing an IAG-based signature to predict the prognosis of MIBC patients. Methods In the present study, we identified differentially expressed IAGs in MIBC by using transcriptomics data from The Cancer Genome Atlas (TCGA) database and proteomics data from our samples. We further constructed an IAG-based signature and evaluated its prognostic and predictive value by survival analysis and nomogram. Tumor Immune Estimation Resource (TIMER) was applied to explore the correlation between the IAG-based signature and immune cell infiltration in the microenvironment of MIBC. Results A total of 22 differentially expressed IAGs were identified, and 2 IAGs (NR2F6 and AHNAK) were used to establish a prognostic signature. Subsequently, survival analysis showed that high-risk scores were significantly correlated with poor overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) of MIBC patients. A prognostic nomogram was constructed by integrating clinical factors with the IAG-based signature risk score. In addition, the IAG-based signature risk score was positively associated with the infiltration of macrophages and dendritic cells in MIBC. Conclusions We constructed and verified a novel IAG-based signature, which could predict the prognosis of MIBC and might reflect the status of the immune microenvironment of MIBC. Further studies in more independent clinical cohorts and further experimental exploration of the prognostic IAG-based signature are still needed.
Highlights
Bladder cancer (BC), a complex tumor associated with high morbidity and mortality rates in the urinary system, is the ninth most common malignant disease worldwide [1]
Characteristic (ROC) curve was conducted to evaluate the predictive accuracy of clinicopathologic characteristics and the immune-associated genes (IAGs) signature with the R package “survivalROC.” univariate and multivariate Cox regression analyses were performed to assess whether the risk score was independent of other clinical variables such as age, gender, grade, stage, pathologic T, pathologic N, pathologic M, and histological subtype in determining the prognosis of the muscle-invasive bladder cancer (MIBC) patients
A nomogram was constructed by integrating clinical variables and the risk score derived from the prognostic signature to assess the probable 1, 2, and 3year overall survival (OS) of MIBC patients via the R package rms [13]
Summary
Immune-associated genes (IAGs) have been documented as having critical roles in the occurrence and progression of muscle-invasive bladder cancer (MIBC). The study is aimed at developing an IAG-based signature to predict the prognosis of MIBC patients. We further constructed an IAG-based signature and evaluated its prognostic and predictive value by survival analysis and nomogram. Tumor Immune Estimation Resource (TIMER) was applied to explore the correlation between the IAG-based signature and immune cell infiltration in the microenvironment of MIBC. A prognostic nomogram was constructed by integrating clinical factors with the IAG-based signature risk score. The IAG-based signature risk score was positively associated with the infiltration of macrophages and dendritic cells in MIBC. We constructed and verified a novel IAG-based signature, which could predict the prognosis of MIBC and might reflect the status of the immune microenvironment of MIBC. Further studies in more independent clinical cohorts and further experimental exploration of the prognostic IAG-based signature are still needed
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