Abstract 4656: Fatty acid β-oxidation enzyme ECI1: a biomarker of poor survival outcome in prostate cancer patients after transurethral resection of the prostate (TURP)

Deregulated mitochondrial fatty acid β-oxidation is known to drive prostate cancer (PCa) pathogenesis. ECI1 (Δ3, Δ2-Enoyl-CoA Delta Isomerase 1) is a key mitochondrial fatty acid β-oxidation enzyme whose role in PCa remains to be explored. We recently showed the impacts of ECI1 on PCa phenotype by modulating its expression in cell lines and assessed the clinical implications of its expression in human prostate tissue samples. ECI1 overexpression increased PCa cell growth and enhanced colony formation, cell motility, and maximal mitochondrial respiratory capacity. PCa cells stably overexpressing ECI1 injected orthotopically in nude mice formed larger prostate tumors with higher number of metastases. Immunohistochemistry analysis of a tissue microarray representing radical prostatectomy cases revealed a stronger ECI1 staining in prostate tumors compared to corresponding benign tissues. ECI1 expression was higher in cases with high tumor grade and advanced tumor stage. ECI1 overexpression was a strong independent predictor of biochemical recurrence after adjusting for known clinicopathologic parameters. ECI1 overexpression was also associated with increased risk of distant metastasis and reduced overall survival, suggesting a key role in disease progression. The purpose of this study was to assess the prognostic value ECI1 expression in PCa tissue on overall survival of patients who underwent palliative transurethral resection of the prostate (TURP). ECI1 immunohistochemistry was performed on a tissue microarray representing 257 TURP cases. ECI1 staining of malignant epithelial cells was assessed using the H-score method and patients were dichotomized into two groups based on ECI1 expression (high vs low). ECI1 overexpression was associated with an increased risk of death, which remained significant after adjusting for age and tumor grade group (hazard ratio=1.57, P=0.01). Moreover, a subgroup of this cohort considered of favorable survival outcome according to their PTEN positive and ERG negative tumor expression statuses (n=121) were further risk stratified by ECI1 even after adjusting for age and tumor grade group (hazard ratio =2.26, P=0.004). Overall, this study supports the contribution of ECI1 to PCa progression and highlights its potential as biomarker to identify patients at high risk of death among those who underwent a palliative TURP procedure. Future studies should explore whether the ECI1 metabolic pathway may serve as therapeutic target to improve patient survival and quality of life. Citation Format: Karl-Philippe Guérard, Elie Fadel, Ryan Antel, Fadi Brimo, Tarek Bismar, Jacques Lapointe. Fatty acid β-oxidation enzyme ECI1: a biomarker of poor survival outcome in prostate cancer patients after transurethral resection of the prostate (TURP) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4656.