13/02-2023 - Jean-Philippe FOY : Impact of unraveling transcriptomic heterogeneity during oral carcinogenesis for precision medicine in patients with oral cancer

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LUNDI 13 FEVRIER 2023

Impact of unraveling transcriptomic heterogeneity during oral carcinogenesis for precision medicine in patients with oral cancer

Jean-Philippe FOY

MCU-PH Sorbonne Université, CRSA Team M. Sabbah

invité par Equipe de Michèle Sabbah (Equipe SABBAH (michele.sabbah@inserm.fr))

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Oral squamous cell carcinoma (OSCC) is the most common site of head and neck cancer and is associated with a substantial morbidity and mortality. OSCC may develop from oral potentially malignant disorders (OPMD), during a multistep process of oral carcinogenesis. Investigating molecular heterogeneity at early and late stage of oral carcinogenesis could help for refining personalized strategies in patients with OPMD/OSCC.
Notably, we identified different biomarkers associated with malignant transformation of oral potentially malignant disorder (OPMD), including DNA methylation markers, gene signatures associated with the dynamic of transcriptome changes, identification of two distinct molecular subtypes of OPMD, and a score of genome instability. We also deciphered transcriptomic heterogeneity of OSCC through three main observations: i- the identification of immune microenvironment as the main actionable difference between oral squamous cell carcinoma (OSCC) from never-smoker never-drinker patients compared to smoker drinker patients; ii- the association of molecular subtypes of HNSCC with the level of radioresistance, as defined by a 13-gene expression score; iii- the identification of immunologically active “hot” tumors who may benefit from immunotherapy. Finally, multimodal characterization of heterogeneity of OSCC, especially by integrating imaging and transcriptomic profiles, could improve the development of precision medicine in patients with OSCC.

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