Abstract C058: Differential DNA methylation in HPV+ and HPV- penile tumors from Puerto Rican men
Authors: Reyes Yarelis M. Roque , Sánchez-Vázquez María , Perez Josué , Llanos Luis R. , Montes Ingrid , Figueroa-Díaz Jasmine , Rivera-Lopez Carlos , Marcos María , Puras Antonio , Martínez-Ferrer Magaly 
Published: December 2023

The incidence of penile squamous cell carcinoma (PSCC) in Puerto Rico is nearly three times higher when compared with other racial and ethnic groups in the United States.  Mortality rate for PSCC is also significantly higher among Puerto Rican men when compared to the US population. Human papillomavirus (HPV) is a common virus, and its infection may increase the risk of developing PeCa. Despite the high incidence, the molecular mechanism of PSCC remains poorly understood.  Our laboratory found that the prevalence of HPV in PSCC in Puerto Rican men is 49%. Due to the high rates of HPV infection and increased incidence of penile cancer in Puerto Rican men, there is a need to understand the pathogenesis of penile cancer. DNA Methylation is an epigenetic alteration that can be found in cancer cells, which can lead to changes in gene expression and cellular function. This study aims to analyze the DNA methylation patterns in HPV-positive and HPV-negative PSCC tissues from Puerto Rican men. DNA was extracted from twenty-four fresh PSCC tissue samples from Puerto Rican patients. HPV status and genotyping were determined using the DNA ELISA kit HPV SPF10 protocol. DNA was amplified and hybridized using PCR. We perform a DNA methylation assay using the Infinium Methylation EPIC v2.0 BeadChip Kit to identify and compare average DNA methylation levels (%) in the 9 HPV-positive and 15 HPV-negative penile cancer samples. Our results demonstrated 43 loci significantly different between HPV-positive and HPV-negative samples, with an adjusted p-value &lt;0.1 (Benjamini-Hochberg method). Most of the hypermethylated loci were present in HPV-negative tumor samples. Additionally, we identified four methylated-differentially expressed genes: ANXA4, CACNA1C-AS1, UBXN2A, and DUOX1, which are found as uncharacterized proteins (open reading frames, ORFs) of the human genome with adjusted p-value &lt;0.05. Studies have revealed that specific DNA methylation patterns could be linked with cancer development and progression. Identification of differentially methylated regions in HPV positive (HPV+) PSCC compared with HPV negative (HPV-) cases will provide much needed data to aid studies on early detection, prognosis, and development of therapeutic agents to reduce the morbidity and mortality from PeCa. Identification of differentially expressed genes and pathways in HPV positive (HPV+) PeCa compared with HPV negative (HPV-) cases will provide much needed data to aid studies on prevention, early detection, prognosis, and development of therapeutic agents to reduce the morbidity and mortality from PeCa.    

Citation Format: Yarelis M. Roque Reyes, María Sánchez-Vázquez, Josué Perez, Luis R. Llanos, Ingrid Montes, Jasmine Figueroa-Díaz, Carlos Rivera-Lopez, María Marcos, Antonio Puras, Magaly Martínez-Ferrer. Differential DNA methylation in HPV+ and HPV- penile tumors from Puerto Rican men [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C058.