Predicting oral squamous cell carcinoma transformation through invasion associated biomarkers in oral epithelial dysplasia

Active Project Grant Awarded Last action

Award ID
F31DE036085
Recipient
Awarding agency
Obligated
$50,914

Award facts

Assistance listing
93.121 Oral Diseases and Disorders Research
Completion date 0% complete
Place of performance
Ann Arbor, MI 48109, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
In the mucosa lining the oral cavity, oral epithelial dysplasia (OED) is a precancer that has a high risk of transforming to oral squamous cell carcinoma (oscc). In pathology practice, OED is graded as mild, moderate, or severe based on histomorphology of the transformed epithelial cells that comprise this lesion. Grading criteria are insufficient due to inter-pathologist variability and inaccurate prediction of oscc progression leading to over treatment of higher-grade oeds that will not progress and under-treatment of lower-grade oeds that do. A molecular biomarker that predicts progression of an OED to oscc would resolve this issue by increasing predictive accuracy of malignant transformation. To discover this biomarker, i will focus on invasion, due to IT being the critical phenotypic difference between oeds and osccs. In this project, invasion is defined as spreading of transformed OED cells from surface epithelium to underlying connective tissue and involves crossing the basement membrane that separates the two. Numerous invasion mechanisms are well studied highlighting that invasion is multifaceted and complex. For this reason, to discover invasion-associated biomarkers that predict progression of OED to oscc, we will use data derived from orthogonal approaches including CPG site DNA methylation (dnam) and whole transcriptome (WTX) single cell-resolution spatial transcriptomics (ST) that was generated from a unique longitudinal cohort (170+ biopsies from 109 patients). This cohort comprises clinical and demographic variables in a redcap database, including OED fates (stable OED or progressor to severe OED or oscc) that have been tracked for over a decade. With this data, i hypothesize that oeds at risk for transformation to oscc will have a molecular profile of invasion-associated biomarkers. To test this hypothesis, aim 1 will focus on identifying invasion associated dnam biomarkers by uncovering invasion processes through an unsupervised approach and focused comparisons between clinical classifications through a supervised approach. Aim 2 focuses on prioritizing, integrating, and validating spatially informed invasion-associated gene biomarkers by comparing expression profiles of regions within and between samples, using machine learning to project dnam derived meta-paths onto the ST samples, then validate the protein expression of the top biomarkers with immunohistochemistry. My results will provide a biomarker signature that predicts invasion in oeds that is derived from transcriptomic, epigenetic, spatial informatics, and validation on the protein level through IHC.

Quick answers

Who received award F31DE036085?

F31DE036085 was awarded to Regents Of The University Of Michigan by National Institute of Dental and Craniofacial Research (National Institutes of Health) on February 15, 2027.

How much is award F31DE036085 worth?

$50,914 has been obligated on F31DE036085.

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