Hispanics/Latinos, Black Americans, and poor Non-Latino Whites in the United States are at higher risk of developing head and neck squamous cell carcinoma (HNSCC). The incidence of HNSCC in Puerto Rico is 2.5 higher than for Hispanics/Latinos living in the United States. These health disparities are a serious public health concern due to HNSCC high mortality and morbidity rates, higher treatment costs, and significant quality of life burden. We hypothesized that the discovery of actionable targets for HNSCC early detection, diagnosis, prognostication. Differentially Methylated Regions (DMRs) can be used as HNSCC diagnostic, prognostic, and therapeutic targets in precision medicine workflows. DNA from 23 HNSCC samples and 10 healthy oral tissue samples from patients in Puerto Rico were hybridized to a genome-wide tiling array to identify DMRs in a discovery cohort. Downstream analyses identified differences in promoter DNA methylation patterns in oral, laryngeal, and oropharyngeal anatomical regions associated with tumor differentiation, nodal involvement, and survival. Genome-wide DMR analysis showed 2,565 DMRs common to the three subsites. We identified 738 DMRs unique to laryngeal cancer (n=7), 889 DMRs unique to oral cavity cancer (n=10), and 363 DMRs unique to pharyngeal cancer (n=6). Based on the genome-wide analysis, and a gene ontology analysis, we selected 10 candidate genes to test for prognostic value and association with clinicopathological features. TIMP3 was associated with tumor differentiation in oral cavity cancer (p =0.039), DAPK1 was associated with nodal involvement in pharyngeal cancer (p = 0.017), and PAX1 was associated with tumor differentiation in laryngeal cancer (p = 0.040). We selected 5 candidate genes, DAPK1, CDH1, PAX1, CALCA, and TIMP3, for a prevalence study in a larger validation cohort: 42 oral cavity; 25 pharyngeal; and 52 laryngeal cancer samples. PAX1 hypermethylation differed across HNSCC anatomic sub-sites (p= 0.029), and predominantly detected in laryngeal cancer. Kaplan-Meier survival analysis (p=0.043) and Cox regression analysis of overall survival (p=0.001) showed that DAPK1 methylation is associated with better prognosis in HNSCC. Our findings show that HNSCC sub-sites (oral cavity, pharynx, and larynx) display substantial differences in aberrant DNA methylation patterns among Hispanic/Latinos HNSCC patients in the US. These data suggest further research may lead to the development of diagnostic medical devices, prognostic biomarkers and novel therapeutic targets that may lead to a reduction in HNSCC disparities among Hispanic/Latinos in the US.
Citation Format: BIanca Rivera-Peña, Oluwasina Folawiyo, Nitesh Turaga, Rosa J. Rodríguez-Benítez, Marco E. Felici, Jaime A. Aponte-Ortiz, Francesca Pirini, Sebastián Rodríguez-Torres, Roger Vázquez, Ricardo López, David Sidransky, Rafael E. Guerrero-Preston, Adriana Báez. Promoter DNA methylation patterns in oral, laryngeal, and oropharyngeal anatomical regions are associated with tumor differentiation, nodal involvement, and survival in Latinos. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5765.
