Senescence-associated lncRNAs indicate distinct molecular subtypes associated with prognosis and androgen response in patients with prostate cancer

Abstract

Cellular senescence has been considered as a hallmark of aging. In this study, we aimed to establish two novel prognostic subtypes for prostate cancer patients using senescence-related lncRNAs. Nonnegative matrix factorization algorithm was used to identify molecular subtypes. We completed analyses using software R 3.6.3 and its suitable packages. Using SNHG1, MIAT and SNHG3, 430 patients in TCGA database were classified into two subtypes associated with biochemical recurrence (BCR)-free survival and subtype 2 was prone to BCR (HR: 19.62, p < 0.001). The similar results were observed in the GSE46602 and GSE116918. For hallmark gene set enrichment, we found that protein secretion and androgen response were highly enriched in subtype 1 and G2M checkpoint was highly enriched in subtype 2. For tumor heterogeneity and stemness, homologous recombination deficiency and tumor mutation burden were significantly higher in subtype 2 than subtype 1. The top ten genes between subtype 2 and subtype 1 were CUBN, DNAH9, PTCHD4, NOD1, ARFGEF1, HRAS, PYHIN1, ARHGEF2, MYOM1 and ITGB6 with statistical significance. In terms of immune checkpoints, only CD47 was significantly higher in subtype 1 than that in subtype 2. For the overall assessment, no significant difference was detected between two subtypes, while B cells score was significantly higher in subtype 1 than subtype 2. Overall, we found two distinct subtypes closely associated with BCR-free survival and androgen response for prostate cancer. These subtypes might facilitate future research in the field of prostate cancer.

Keywords

• prostate cancer
• biochemical recurrence
• cellular senescence
• nonnegative matrix factorization
• molecular subtypes
• androgen response