Abstract
Early detection of head and neck cancers (HNCa) correlate with improved outcomes. Salivary proteins may potentially be used for effective screening, which may result in increased survival time. This project aims to find potential biomarkers for laryngeal cancer, which ultimately could be detected by testing saliva or a swab of the back of the mouth. These simple screening methods would be of great benefit to high-risk individuals, and could potentially decrease disparities seen between minorities and white Americans. African American (AA) and white American (WA) men share similar incidences of laryngeal and tonsillar cancer, which affect men at a much higher rate than women. Among AA and WA men there is an alarming disparity, in which AA men are two to three times more likely to succumb to their disease. It is hypothesized that the salivary proteomes for tonsillar and laryngeal cancer, from AA and WA men, possess prognostic potential illustrating an association with the molecular characteristics of the tumor. MUDPIT proteomic analysis was done on four groups of pooled samples, four per group. Samples were collected with the approval of the Meharry Medical College Institutional Review Board. Inclusion criteria were males diagnosed with late stage (III or IV) laryngeal or tonsillar HNCa, active smokers, and HPV negative. Exclusion criteria were non-smokers and HPV positive. Groups were designated as AA/T, WA/T, AA/L and WA/L. A total number of 117 proteins were identified. AA/L had 111 proteins while WA/L had 116 proteins. Twenty proteins were detected from 1.6-fold to 1.62E+06 –fold greater in AA/L relative to WA/L. Eighty proteins were detected from 1.5-fold to 7.9E+07-fold greater in WA/L relative to AA/L. The resulting salivary proteomes were analyzed using WebGestalt. Pathway analysis for AA/L vs WA/L showed significant alignment with Reactome pathways. 8 proteins were found to be associated with innate immune function. There were no significant categories for enrichment category disease_Disgenet, however several proteins aligned with cancer categories at a non-significant level, such as annexin A1. Disease_GLAD4U recognized a statistically significant enrichment category of dental plaque. Represented proteins include CA6, PRH1 and MUC5B. Pathway analysis with KEGG, Panther and Reactome, were used for proteins greater in WA/L, and revealed overrepresentation of proteins associated with metabolic activity, hypoxia and the innate immune system. In addition, disease_disgenet showed proteins mapping to mouth neoplasms, SCC of esophagus, and cancer invasion. Finally, GLAD4U showed significance with periodontal diseases, ischemia and inflammation. A limitation of this research is the small sample size, nevertheless the potential differences between racial groups promotes further investigation. Exploration of these specific proteins or protein signatures can give insight into varying physiological responses to disease and can be used to create a more personalized therapeutic approach.
Citation Format: Derek Wagner, Hannah Trew, Billy Ballard, Victor Paramov, Sid Pratap, Dana Marshall. The salivary proteome of African American and white American males diagnosed with laryngeal cancer [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D129.