Abstract 9: Association Between HMOX1 (GT)n Promoter Microsatellite and Prostate Cancer Prognosis
Authors: Pascual Gaston , Sabater Agustina , Seniuk Rocio , Achinelli Ines , Freiria Pamela , Scorticati Carlos , Mazza Osvaldo , Toro Ayelen , Vazquez Elba , Gueron Geraldine , Cotignola Javier 
Published: June 2023

Purpose: Heme Oxygenase 1 (HO-1), the rate-limiting enzyme in heme degradation encoded by HMOX1 gene, has a strong anti-tumoral effect in prostate cancer (PCa). HMOX1 expression levels are modulated by the length of a dinucleotide (GT)n microsatellite polymorphism mapping in its promoter region. PCa is the second most frequent cancer and the sixth leading cause of cancer-related deaths in men worldwide. One of the strongest predictors for newly diagnosed PCa is the International Society of Urological Pathology (ISUP) grade, a histopathology-based classification system, which presents diverse limitations due to tumoral heterogeneity. Consequently, the identification of novel biomarkers is important to optimize PCa prognosis. In this study we genotyped the HMOX1 (GT)n promoter polymorphism and analyze its association with PCa clinico-pathological parameters.

Methods: We collected 108 peripheral blood samples from PCa patients from Hospital de Clínicas “Jose de San Martín”, Buenos Aires, Argentina. Genomic DNA was isolated and the (GT)n was genotyped by fluorescent PCR and capillary electrophoresis. Randomly selected samples were cloned and sequenced by Sanger to determine the length of the microsatellite and validate the results. We considered a statistically significant difference between groups if p≤0.05.

Results: The length of the (GT)n ranged from 11 to 40 repeats. HMOX1 alleles were dichotomized as “Long (l)” (≥30 repeats) or “Short (s)” (&lt;30 repeats) based on the median length; and genotypes were categorized as homozygous “HMOX1ss, homozygous “HMOX1ll”, or heterozygous “HMOX1sl”. We found an association between the “HMOX1ss” genotype and higher serum prostate specific antigen (sPSA) levels among patients with &lt;10 ng/mL sPSA (p&lt;0.01). Furthermore, the proportion of “HMOX1ss” patients increased with the ISUP grade, whereas “HMOX1ll” or “HMOX1sl” genotypes were more frequent in lower ISUP grades (ptrend&lt;0.05). Finally, “HMOX1ss” patients had 4-fold higher risk of biochemical relapse (HR=4.03, p&lt;0.05).

Conclusion: “HMOX1ss” patients present more aggressive phenotypes compared with the other genotypes. HMOX1 polymorphism has the potential to classify patients in different groups to predict the severity of PCa tumors, thus evidencing potential to support clinicians on the decision making and improving clinical management of PCa at an early stage through a non-invasive sample.

Citation Format: Gaston Pascual, Agustina Sabater, Rocio Seniuk, Ines Achinelli, Pamela Freiria, Carlos Scorticati, Osvaldo Mazza, Ayelen Toro, Elba Vazquez, Geraldine Gueron, Javier Cotignola. Association Between HMOX1 (GT)n Promoter Microsatellite and Prostate Cancer Prognosis [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 9.