In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 6_suppl ( 2023-02-20), p. 259-259
Abstract:
259 Background: Histological subtypes of Pca are generally associated with worse clinical outcomes. Here in, we hypothesize that histological subtypes of PCa, e.g., cribriform, and signet ring-like, may have distinct genomic characteristics that may unravel new therapeutic targets. Methods: In this IRB-approved study, patient-level data were collected retrospectively. Eligibility: Pathology slides of advanced PCa (with cribriform and signet ring-like histology, and non-cribriform/signet ring-like histology as control) with transcriptomic data available. Only Gleason grade 4 or 5 were included to ensure homogeneity in population. Histology was independently reviewed by two genitourinary pathologists. RNA-sequencing of treatment naive primary prostate tissue was performed by a CLIA certified lab. DeSeq2 analysis was implemented in Bioconductor Software to analyze differentially expressed genes in patients with cribriform versus non-cribriform and signet ring-like versus non-signet ring-like histology. DeSeq2 results included the Log2 Fold change, Wald-Test p-values, and Benjamini-Hochberg adjusted p-values for each differentially expressed gene. These results were then subjected to Gene Set Enrichment Analysis (GSEA) in order to identify pathways upregulated or downregulated in each cohort. All bioinformatic analysis was conducted in R-Studio, version 4.1.1. Statistical significance level was predetermined at 0.05. Results: 34 patients were included: cribriform histology n=17, signet ring-like n=4, control non-cribriform/signet ring-like PCa n=13 (control were matched for age, PSA and disease volume). Compared to control, upregulated pathways in cribriform histology included adipogenesis, fatty acid and xenobiotic metabolism, while the down regulated pathways included mitotic spindle, G2M checkpoint and E2F targets. In signet ring-like histology, inflammatory response pathways were upregulated; DNA repair, MYC targets and androgen response pathways were downregulated. Conclusions: Cribriform, and signet ring-like histologic subtypes were noted to have distinct genomic expression profile. These data may need further validation and will guide further drug development.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2023.41.6_suppl.259
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2023
detail.hit.zdb_id:
2005181-5
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