Abstract
Oral cavity and oropharynx cancers develop in sites with visual access; despite that, most patients are diagnosed with advanced disease. Finding an ideal biomarker for disease early diagnosis may be challenging, due to the molecular complexity of head and neck carcinomas, in which carcinogenesis may be influenced by diverse risk factors, such as tobacco, alcohol consumption and HPV infection, modulated by the microbiota and the host's immune response. Our proposal is to integrate data from multiple platforms to investigate effective approaches for the early detection of oral and oropharyngeal cancers. For this goal, we will analyze biological samples (tissue, blood and saliva) and images (lesions), including tobacco-exposed mucosa of individuals with no visible lesions, premalignant lesion with and without dysplasia, adjacent mucosa of individuals with cancer and corresponding malignant lesion, with reference to the mucosa of non-smokers. In a discovery phase, lesions will be analyzed by optical spectroscopy and biopsy fragments and biofluids will be analyzed through a comprehensive array of high throughput techniques, in search of biomarkers for the early cancer diagnosis, such as whole exome sequencing, methylomics, transcriptomics, proteomics, metabolomics, metagenomics, and immune Driles. Biopsy fragments will also be analyzed by infrared and RAMAN spectroscopy. Epidemiological data and a photograph of lesion will be obtained from the participants, in another two related projects and analyzed concomitantly with molecular data from the present project. An integrated analysis of all data will be performed in an attempt to unravel patterns and biomarkers to be validated in a second, independent cohort. In the validation phase, analysis will be focused on a subset of targets identified in the discovery phase. Afterwards, the top biomarkers for the early detection of cancer will be used to assemble biosensors or other low-cost devices to be further tested in a future project. This project is divided into six work packages and will be integrated to two complementary projects, that will characterize participants for epidemiological factors and malignant patterns in the lesions´ photographs.Work package 1: Histological analysis correlation with optical spectroscopy of the lesion - autofluorescence, infrared and RAMAN;Work package 2: Whole Exome Sequencing (WES), transcriptomics and methylomics to detect tumor molecular targets to be investigated by liquid biopsy;Work package 3: Liquid biopsy to assess circulating tumor cells (CTCs), tumor DNA, RNA and DNA methylation markers.Work package 4: Proteomics, metabolomics and lipidomics in tumor and tissue samples and in saliva;Work package 5: Metagenomics, HPV genotyping and immune system characteristics;Work package 6: Radiomics and multidimensional data integration.This study will comprise two phases:Discovery phase: Optical spectroscopy of the lesions and multiple omics will be used to analyze tissue samples and/or biofluids from participants affected with cancer vs premalignant lesions or normal mucosa (reference), with the goal of mining potential diagnosis biomarkers.Validation phase: Optical spectroscopy characteristics of the lesions allied with candidate biomarkers (identified in the discovery phase) will be investigated in a second cohort of participants, to verify the association with cancer. (AU)
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