Association of obesity with tumor differential gene expression and gene set enrichment pathways in advanced prostate adenocarcinoma (PCa).

231 Background: Increased Body Mass Index (BMI) has been linked to increased prostate cancer incidence, recurrence, and mortality (PMID: 35538398). Herein, we sought to investigate the underlying differences in gene expression profiles based on BMI in patients (pts) with PCa. Methods: In this IRB-approved retrospective study, eligibility criteria included histologically confirmed PCa and available RNA sequencing results from treatment naïve primary prostate tissue by a CLIA-certified lab. Pts were categorized into two cohorts: obese (Ob, BMI≥30) and non-obese (non-Ob, BMI<30). BMI at the time of diagnosis of PCa was used for analysis. The DEseq2 pipeline was used to analyze differentially expressed genes between the groups. The data included the Log2 fold change, Wald-Test p-values, and Benjamini-Hochberg adjusted p-values (q values) for each differentially expressed gene. These results were subjected to Gene Set Enrichment software analysis (GSEA) to identify pathways enriched in each cohort. All bioinformatic analysis was undertaken using R v4.2. Results: 60 pts were eligible, of which 22 were Ob and 38 were non-Ob. Tumor tissues from Ob pts had an increased expression of the heme metabolism, androgen-response, protein secretion, fatty acid, and bile metabolism pathways. Non-Ob pts had a significantly higher expression of genes involved in the inflammation pathways (interferon-alpha & TNF alpha pathways). Normalized enrichment scores are reported. Differential individual gene expression profiles will be presented at the meeting. Conclusions: Our study showed upregulation of distinct genomic pathways in Ob pts with prostate cancer which may help personalize medicine and guide further drug development. These hypothesis-generating data require external validation. [Table: see text]