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CD44, gamma-H2AX, and p-ATM Expressions in Short-Term Ex Vivo Culture of Tumour Slices Predict the Treatment Response in Patients with Oral Squamous Cell Carcinoma

Abstract : Squamous cell carcinoma is the most common type of head and neck cancer (HNSCC) with a disease-free survival at 3 years that does not exceed 30%. Biomarkers able to predict clinical outcomes are clearly needed. The purpose of this study was to investigate whether a short-term culture of tumour fragments irradiated ex vivo could anticipate patient responses to chemo- and/or radiotherapies. Biopsies were collected prior to treatment from a cohort of 28 patients with non-operable tumours of the oral cavity or oropharynx, and then cultured ex vivo. Short-term biopsy slice culture is a robust method that keeps cells viable for 7 days. Different biomarkers involved in the stemness status (CD44) or the DNA damage response (pATM and gamma-H2AX) were investigated for their potential to predict the treatment response. A higher expression of all these markers was predictive of a poor response to treatment. This allowed the stratification of responder or non-responder patients to treatment. Moreover, the ratio for the expression of the three markers 24 h after 4 Gy irradiation versus 0 Gy was higher in responder than in non-responder patients. Finally, combining these biomarkers greatly improved their predictive potential, especially when the gamma-H2AX ratio was associated with the CD44 ratio or the pATM ratio. These results encourage further evaluation of these biomarkers in a larger cohort of patients.
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https://hal-u-picardie.archives-ouvertes.fr/hal-03599302
Contributeur : Louise Dessaivre Connectez-vous pour contacter le contributeur
Soumis le : lundi 7 mars 2022 - 09:51:18
Dernière modification le : vendredi 6 mai 2022 - 09:30:09

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Pierre Philouze, Arnaud Gauthier, Alexandra Lauret, Céline Malésys, Giovanna Muggiolu, et al.. CD44, gamma-H2AX, and p-ATM Expressions in Short-Term Ex Vivo Culture of Tumour Slices Predict the Treatment Response in Patients with Oral Squamous Cell Carcinoma. International Journal of Molecular Sciences, MDPI, 2022, 23 (2), ⟨10.3390/ijms23020877⟩. ⟨hal-03599302⟩

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