Identification of a minimal biomarker profile in head-and-neck squamous cell carcinoma tumors
Identification of a minimal biomarker profile in head-and-neck squamous cell carcinoma tumors
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.
Mu?oz-Galvan Sandra、Verdugo-Sivianes Eva M、Rodrigo Juan P.、Sanchez-Diaz Laura、Navas Lola E.、Felipe-Abrio Blanca、Garcia-Mayea Yoelsis、Celis-Romero Manuel A.、LLeonart Matilde E.、Chiara Maria-Dolores、Carnero Amancio、Garcia-Heredia Jose Manuel、Carracedo Angel、Fern¨￠ndez-Rozadilla Ceres、Suarez-Martinez Elisa、Chaves-Conde Manuel
Instituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocio, Universidad de Sevilla, Consejo Superior de Investigaciones Cientificas||Spanish Biomedical Research Network Centre in Oncology, CIBERONC, Instituto de Salud Carlos IIIInstituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocio, Universidad de Sevilla, Consejo Superior de Investigaciones Cientificas||Spanish Biomedical Research Network Centre in Oncology, CIBERONC, Instituto de Salud Carlos IIISpanish Biomedical Research Network Centre in Oncology, CIBERONC, Instituto de Salud Carlos III||Department of Otolaryngology, Hospital Universitario Central de Asturias, ISPA, University of Oviedo, IUOPAInstituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocio, Universidad de Sevilla, Consejo Superior de Investigaciones Cientificas||Spanish Biomedical Research Network Centre in Oncology, CIBERONC, Instituto de Salud Carlos IIIInstituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocio, Universidad de Sevilla, Consejo Superior de Investigaciones Cientificas||Spanish Biomedical Research Network Centre in Oncology, CIBERONC, Instituto de Salud Carlos IIILaboratory of Cell Death Research and Therapy, Department for Cellular and Molecular Medicine, Campus Gasthuisberg, University of Leuven (KU Leuven)Biomedical Research in Cancer Stem Cells, Vall d?ˉHebron Research Institute (VHIR)Instituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocio, Universidad de Sevilla, Consejo Superior de Investigaciones CientificasBiomedical Research in Cancer Stem Cells, Vall d?ˉHebron Research Institute (VHIR)Spanish Biomedical Research Network Centre in Oncology, CIBERONC, Instituto de Salud Carlos III||Instituto de Investigaci¨?n Sanitaria del Principado de AsturiasInstituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocio, Universidad de Sevilla, Consejo Superior de Investigaciones Cientificas||Spanish Biomedical Research Network Centre in Oncology, CIBERONC, Instituto de Salud Carlos IIIInstituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocio, Universidad de Sevilla, Consejo Superior de Investigaciones Cientificas||Spanish Biomedical Research Network Centre in Oncology, CIBERONC, Instituto de Salud Carlos IIIInstituto de Investigaci¨?n Sanitaria de Santiago (IDIS)||Grupo de Medicina Xen¨?mica, CIBERER, Universidad de Santiago de Compostela||Fundaci¨?n P¨2blica Galega de Medicina Xen¨?mica, SERGASInstituto de Investigaci¨?n Sanitaria de Santiago (IDIS)||Grupo de Medicina Xen¨?mica, CIBERER, Universidad de Santiago de CompostelaInstituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocio, Universidad de Sevilla, Consejo Superior de Investigaciones Cientificas||Spanish Biomedical Research Network Centre in Oncology, CIBERONC, Instituto de Salud Carlos IIIInstituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocio, Universidad de Sevilla, Consejo Superior de Investigaciones Cientificas||Spanish Biomedical Research Network Centre in Oncology, CIBERONC, Instituto de Salud Carlos III||Medical Oncology Department, Hospital de Valme
肿瘤学基础医学分子生物学
HNSCC tumorsstemnesstranscriptional alterationsbiomarkerscancertumorigenesis
Mu?oz-Galvan Sandra,Verdugo-Sivianes Eva M,Rodrigo Juan P.,Sanchez-Diaz Laura,Navas Lola E.,Felipe-Abrio Blanca,Garcia-Mayea Yoelsis,Celis-Romero Manuel A.,LLeonart Matilde E.,Chiara Maria-Dolores,Carnero Amancio,Garcia-Heredia Jose Manuel,Carracedo Angel,Fern¨￠ndez-Rozadilla Ceres,Suarez-Martinez Elisa,Chaves-Conde Manuel.Identification of a minimal biomarker profile in head-and-neck squamous cell carcinoma tumors[EB/OL].(2025-03-28)[2025-05-12].https://www.biorxiv.org/content/10.1101/2021.11.12.468359.点此复制
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