Identification of a minimal biomarker profile in head-and-neck squamous cell carcinoma tumors

Sanchez-Diaz, L.; Navas, L. E.; Suarez-Martinez, E.; Felipe-Abrio, B.; Fernandez-Rozadilla, C.; Verdugo-Sivianes, E. M.; Celis-Romero, M. A.; Chaves-Conde, M.; Chiara, M.-D.; Garcia-Mayea, Y.; LLeonart, M. E.; Garcia-Heredia, J. M.; Munoz-Galvan, S.; Carracedo, A.; Rodrigo, J. P.; Carnero, A.

doi:10.1101/2021.11.12.468359

bioRxiv · 10.1101/2021.11.12.468359

Identification of a minimal biomarker profile in head-and-neck squamous cell carcinoma tumors

Sanchez-Diaz, L.·Navas, L. E.·Suarez-Martinez, E.·Felipe-Abrio, B.·Fernandez-Rozadilla, C.·Verdugo-Sivianes, E. M.·Celis-Romero, M. A.·Chaves-Conde, M.·Chiara, M.-D.·Garcia-Mayea, Y.·LLeonart, M. E.·Garcia-Heredia, J. M.·Munoz-Galvan, S.·Carracedo, A.·Rodrigo, J. P.·Carnero, A.

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Abstract

Although important advances have been made in the knowledge of the molecular mechanisms leading to the development, of head and neck squamous cell carcinoma (HNSCC), only PDL1 is used for the immunotherapy (pemborlizumab) treatment in the first line of metastatic or recurrent disease. There are no other molecular biomarkers currently used in clinical practice. The objective of the study was to identify transcriptional alterations in patients with oral cavity cancer that identify gene networks responsible for resistance to treatment and prognosis. To identify possible targets for the treatment or prevention of these tumors, we screened for changes in transcription of genes that were recurrently altered in patients and that successfully stratify tumoral and non-tumoral samples, as well as patient survival, based on expression levels. The gene panels are primarily related to the cell cycle, DNA damage response, cytokine signaling and the immune system but also to the embryonic stem cell core. Validation of these panels in an independent cohort led to the identification of three non-interconnected genes, WDR66, SERPINH1 and ZNF622, that can predict patient survival and are differentially expressed in 3D cultures from HNSCC primary cell lines. These genes are related to stemness phenotype are transcriptional targets of the pluripotency transcription factors Sox2 and c-Myc. Our results suggest that WDR66, SERPINH1 and ZNF622 con-stitute a minimal signature of stemness transcriptional targets able to predict the prognosis of HNSCC tumors. Simple SummaryThe objective of the study was to identify transcriptional alterations in patients with oral cavity cancer to possibly identify gene networks responsible for resistance to treatment and prognosis. We identify bioinformatically gene panels are primarily related to the cell cycle, DNA damage response, cytokine signaling and the immune system but also to the embryonic stem cell core. Validation of these panels in patients independent cohorts led to the identification of three non-interconnected genes, WDR66, SERPINHl and ZNF622, that can predict patient survival and are differentially expressed in cancer stem cells cultures from HNSCC. These genes are related to stemness phenotype and epithelial-to-mesenchymal transition and are transcriptional targets of the pluripotency transcription factors Sox2 and c-Myc.

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Sanchez-Diaz, L., Navas, L. E., Suarez-Martinez, E., Felipe-Abrio, B., Fernandez-Rozadilla, C., Verdugo-Sivianes, E. M., Celis-Romero, M. A., Chaves-Conde, M., Chiara, M.-D., Garcia-Mayea, Y., LLeonart, M. E., Garcia-Heredia, J. M., Munoz-Galvan, S., Carracedo, A., Rodrigo, J. P., Carnero, A.. 2021-11-17. Identification of a minimal biomarker profile in head-and-neck squamous cell carcinoma tumors. https://doi.org/10.1101/2021.11.12.468359

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