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Distinct molecular subtypes associated with prognosis and androgen response in patients with prostate cancer

August 10th, 2023
Distinct molecular subtypes associated with prognosis and androgen response in patients with prostate cancer
Prognostic value of subtypes and pathway analysis. (a) Kaplan-Meier curve showing the BCR-free survival difference in TCGA database. (b) Heatmap plot showing two distinct subtypes in GSE116918. (c) Kaplan-Meier curve showing the BCR-free survival difference in GSE116918. (d) Heatmap plot showing two distinct subtypes in the GSE46602. (e) Kaplan-Meier curve showing the BCR-free survival difference in GSE46602. (f) Hallmark gene set analysis of TCGA subtypes. (g) KEGG pathway differences in TCGA subtypes. (h) Forest plot showing results of tumor heterogeneity and stemness between TCGA subtypes. (i) Waterfall plot showing the top ten differentially mutated genes between TCGA subtypes. BCR, biochemical recurrence. Credit: Acta Materia Medica (2023). DOI: 10.15212/AMM-2023-0025

Cellular senescence has been considered a hallmark of aging. The authors of a new publication in Acta Materia Medica aimed to establish two novel prognostic subtypes for prostate cancer patients using senescence-related lncRNAs.

A nonnegative matrix factorization algorithm was used to identify molecular subtypes. Analyses were completed 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).

Similar results were observed in GSE46602 and GSE116918. For hallmark gene set enrichment, it was 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 10 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, two distinct subtypes closely associated with BCR-free survival and androgen response for prostate cancer were found. These subtypes might facilitate future research in the field of prostate cancer.

More information:
Dechao Feng et al, Senescence-associated lncRNAs indicate distinct molecular subtypes associated with prognosis and androgen response in patients with patients with prostate cancer, Acta Materia Medica (2023). DOI: 10.15212/AMM-2023-0025

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