Prognostic significance of B cell senescence-associated genes as risk markers in prostate adenocarcinoma.

Abstract

Background: Prostate adenocarcinoma (PRAD) is a common male urinary system cancer, and its targeted treatment is difficult. This study aimed to investigate the value of B cell senescence-related genes in PRAD prognosis.

Methods: PRAD sample expression and clinical information were downloaded from The Cancer Genome Atlas (TCGA) Program and Gene Expression Omnibus (GEO) databases, and B cell senescence-related gene sets were obtained from the Genecards library. The prognostic model was constructed by univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses of PRAD differentially expressed genes significantly related to B cell senescence. The Kaplan-Meier (K-M) survival curve and receiver operating characteristic (ROC) curve were drawn to verify the survival rate difference between the high and low risk score groups of the model. The differences of immune characteristics between high and low risk groups were evaluated by single sample gene set enrichment analysis (ssGSEA), ESTIMATE and CIBERSORT. The tumor mutation burden (TMB) score was used to assess the variation in genomic mutations across the groups. Small molecule drugs were screened through the GDSC library. Ultimately, in order to examine the risk assessment model's practicality, a nomogram was created.

Results: Three genes WNT16, INS and BMP2 related to PRAD progression and B cell senescence were selected to construct a prognostic risk assessment model. The K-M survival curve and ROC curve verified the good performance in evaluating the prognosis of patients. In terms of immune characteristics, the high-risk score group of the model showed a higher overall immune score and immune cell infiltration level, and the high-risk group showed a relatively higher TP53 and TTN mutation frequency. Drug sensitivity analysis showed that the high-risk group had higher resistance to Camptothecin, Cisplatin and WIKI4 drugs. At last, the nomogram that is created using pathological characteristics in conjunction with the risk score can reliably assess the prognosis of patients with PRAD.

Conclusions: This study constructed and verified a B cell senescence-related gene model that can predict prognosis of PRAD. More importantly, it provides a reference standard for guiding the prognosis of PRAD patients.