Referencia: GIUV2021-507 (Universitat de València).
IP: José Vte. Bagán Sebastián.
Curriculum IP
PubMed:
https://pubmed.ncbi.nlm.nih.gov/?term=bagan+j&sort=date&size=200
https://pubmed.ncbi.nlm.nih.gov/?term=bagan-sebastian&sort=date&size=200

Oral cancer and oropharyngeal cancers are growing problems and the considerable mortality of patients suffering from oral cancer has not decreased substantially in the last 40 years, with a 5-year mortality rate close to 50%. Approximately 50% of OSCCs are currently being diagnosed at an advanced tumour stage, with an increased tumour size (T3/T4). It has been described that 30% of oral cancer patients delay seeking help for more than 3 months after they first notice signs and symptoms of the disease. Although biopsy is the gold standard in the diagnosis of oral cancer it is clear that early diagnosis is essential for better survival. This has motivated the development of research to develop diagnostic methods that help us to orientate the presence of the malignant neoplasia before performing the biopsy.

This is our motivating aim for the research in different fields such as artificial intelligence, as well as at the genetic level and in the oral microbiota in saliva.

Our group was able to carry out research at the level of artificial intelligence (deep Learning) on precancerous lesions, orienting those patients with the highest risk of developing cancer through a project funded by the Fondo de Investigación Sanitaria, ISCIII (2019-2022)(PI19/00790) where we proved the great usefulness of AI in the diagnosis of cancer. This was published in Oral Oncology (first Decil of JCR. Ferrer-Sánchez A, Bagan J, Vila-Francés J, Magdalena-Benedito R, Bagan-Debon L. Prediction of the risk of cancer and the grade of dysplasia in leukoplakia lesions using deep learning. Oral Oncol. 2022 Sep;132:105967. https://doi.org/10.1016/j.oraloncology.2022.105967 Epub 2022 Jun 25. PMID: 35763911). Therefore, our first working hypothesis is that the same IA model that we applied in pre-cancer would allow us to distinguish neoplastic lesions and essentially with the aim of identifying early oral cancer lesions.

At the same time, and at the omic level, and within this same project that we carried out through the ISCIII, we analized the changes in DNA methylation in patients with precancer (This was published in Oral Oncology, first Decil of JCR. Herreros-Pomares A, Llorens C, Soriano B, Bagan L, Moreno A, Calabuig-Fariñas S, Jantus-Lewintre E, Bagan J. Differentially methylated genes in proliferative verrucous leukoplakia reveal potential malignant biomarkers for oral squamous cell carcinoma. Oral Oncol. 2021 May;116:105191. https://doi.org/10.1016/j.oraloncology.2021.105191 Epub 2021 Feb 28. PMID: 33657465). Our results showed that there were clear epigenetic alterations in the biopsies of these patients.

We also investigated alterations in RNAseq (This was published in a journal, first quartil of JCR. Llorens C, Soriano B, Trilla-Fuertes L, Bagan L, Ramos-Ruiz R, Gamez-Pozo A, Peña C, Bagan JV. Immune expression profile identification in a group of proliferative verrucous leukoplakia patients: a pre-cancer niche for oral squamous cell carcinoma development. Clin Oral Investig. 2021 May;25(5):2645-2657. doi: 10.1007/s00784-020-03575-z. Epub 2020 Sep 11. PMID: 32918120) and in the microbiota (This was published in Oral Oncology, first Decil of JCR. Herreros-Pomares A, Llorens C, Soriano B, Zhang F, Gallach S, Bagan L, Murillo J, Jantus-Lewintre E, Bagan J. Oral microbiome in Proliferative Verrucous Leukoplakia exhibits loss of diversity and enrichment of pathogens. Oral Oncol. 2021 Sep;120:105404. doi: 10.1016/j.oraloncology.2021.105404. Epub 2021 Jul 2. PMID: 34225130.).

If we link our previous research described above with our recent European Horizon 2020 project where we analysed molecular markers in pre-cancer and oral cancer in “saliva”, our second working hypothesis is that, just as we found changes in methylation, RNAseq and microbiota in biopsies, they would also exist in saliva, thus giving continuity to our line of research carried out in Horizon 2020 (2016-2020). H2020-MSCA-ITN-2016.

EQUIPO/PERSONAL DE INVESTIGACIÓN

INVESTIGADORES/AS BÁSICOS:
– José Vicente Bagán Sebastián. Director. Catedrático de Medicina Oral de la Universitat de València y jefe del servicio de Estomatología y Cirugía Maxilofacial. bagan@uv.es
– Leticia Bagán Debón. Profesora titular de Medicina Bucal de la Universitat de València. leticia.bagan@uv.es
– Enrique Zapater Latorre. Profesor titular del Departamento de Cirugía de la Universitat de Valencia. Jefe Servicio de ORL. zapater_enr@gva.es
– Juan Sandoval del Amor. Instituto de Investigación Sanitaria La Fe (Valencia). Jefe de la Unidad de Epigenómica del Instituto de Investigación Sanitaria La FE de Valencia. epigenomica@iislafe.es
– Joan Vila Francés. Profesor titular de ingeniería electrónica de la Universitat de Valencia. Escuela superior de ingeniería de la Universitat de Valencia. joan.vila@uv.es
– Leo Arribas. Fundación Instituto Valenciano de Oncología. Jefe del servicio de Radioterapia Oncológica del IVO Valencia. larribas@fivo.org
– David Hervás Marín. Profesor permanente laboral en la Universitat Politècnica de València (UPV). Dpto. de Estadística e Investigación Operativa Aplicadas y Calidad. daherma@upv.edu.es
– Concepción Gimeno Cardona. Jefa del servicio de Microbiología. Profesora Titular de la Universitat de València, desde 1992, adscrita al Departamento de Microbiología i Ecología. cgimenocar@gmail.com
– Judith Murillo Cortés. Jefa de sección del servicio de Estomatología y Cirugía Maxifacial. jumucor@alumni.uv.es

PUBLICACIONES

– Herreros-Pomares A, Hervás D, Bagan-Debon L, Proaño A, Garcia D, Sandoval J, Bagan J. Oral cancers preceded by proliferative verrucous leukoplakia exhibit distinctive molecular features. Oral Dis. 2023 Mar 9. doi: 10.1111/odi.14550. Epub ahead of print. PMID: 36892444.

– Herreros-Pomares A, Hervás D, Bagan-Debón L, Jantus-Lewintre E, Gimeno- Cardona C, Bagan J. On the Oral Microbiome of Oral Potentially Malignant and Malignant Disorders: Dysbiosis, Loss of Diversity, and Pathogens Enrichment. Int J Mol Sci. 2023 Feb 9;24(4):3466. doi: 10.3390/ijms24043466. PMID: 36834903; PMCID: PMC9961214.

– Pentenero M, Sutera S, Lodi G, Bagan JV, Farah CS. Oral leukoplakia diagnosis and treatment in Europe and Australia: Oral Medicine Practitioners’ attitudes and practice. Oral Dis. 2022 Jul 6. doi: 10.1111/odi.14301. Epub ahead of print. PMID: 35792047.

– Bagan J, Martorell M, Cebrián JL, Rubert A, Bagán L, Mezquida C, Hervás D.Effect of clinical and histologic features on time to malignancy in 224 cases of oral leukoplakia treated by surgery. Clin Oral Investig. 2022 Aug;26(8):5181-5188. doi: 10.1007/s00784-022-04486-x. Epub 2022 Apr 26. PMID: 35474554; PMCID: PMC9381619.

– Ferrer-Sánchez A, Bagan J, Vila-Francés J, Magdalena-Benedito R, Bagan-Debon L. Prediction of the risk of cancer and the grade of dysplasia in leukoplakia lesions using deep learning. Oral Oncol. 2022 Sep;132:105967. doi: 10.1016/j.oraloncology.2022.105967. Epub 2022 Jun 25. PMID: 35763911.

– Principe S, Zapater-Latorre E, Arribas L, Garcia-Miragall E, Bagan J. Salivary IL-8 as a putative predictive biomarker of radiotherapy response in head and neck cancer patients. Clin Oral Investig. 2022 Jan;26(1):437-448. doi: 10.1007/s00784-021-04017-0. Epub 2021 Jul 12. PMID: 34251535; PMCID: PMC8791883.

– Herreros-Pomares A, Llorens C, Soriano B, Zhang F, Gallach S, Bagan L, Murillo J, Jantus-Lewintre E, Bagan J. Oral microbiome in Proliferative Verrucous Leukoplakia exhibits loss of diversity and enrichment of pathogens. Oral Oncol. 2021 Sep;120:105404. doi: 10.1016/j.oraloncology.2021.105404. Epub 2021 Jul 2. PMID: 34225130.

– Ramos-García P, González-Moles MÁ, Mello FW, Bagan JV, Warnakulasuriya S. Malignant transformation of oral proliferative verrucous leukoplakia: A systematic review and meta-analysis. Oral Dis. 2021 Nov;27(8):1896-1907. doi: 10.1111/odi.13831. Epub 2021 May 19. PMID: 34009718.

– Dikova V, Jantus-Lewintre E, Bagan J. Potential Non-Invasive Biomarkers for Early Diagnosis of Oral Squamous Cell Carcinoma. J Clin Med. 2021 Apr 13;10(8):1658. doi: 10.3390/jcm10081658. PMID: 33924500; PMCID: PMC8070511.

– Herreros-Pomares A, Llorens C, Soriano B, Bagan L, Moreno A, Calabuig-Fariñas S, Jantus-Lewintre E, Bagan J. Differentially methylated genes in proliferative verrucous leukoplakia reveal potential malignant biomarkers fororal squamous cell carcinoma. Oral Oncol. 2021 May;116:105191. doi: 10.1016/j.oraloncology.2021.105191. Epub 2021 Feb 28. PMID: 33657465.

– Warnakulasuriya S, Kujan O, Aguirre-Urizar JM, Bagan JV, González-Moles MÁ, Kerr AR, Lodi G, Mello FW, Monteiro L, Ogden GR, Sloan P, Johnson NW. Oral potentially malignant disorders: A consensus report from an international seminar on nomenclature and classification, convened by the WHO Collaborating Centre for Oral Cancer. Oral Dis. 2021 Nov;27(8):1862-1880. doi: 10.1111/odi.13704. Epub 2020 Nov 26. PMID: 33128420.

ORGANISMOS FINANCIADORES (FONDOS)

– Proyecto europeo competitivo (The European Commission Framework Programme for Research and Innovation – Horizon 2020, titulado: Training in Cancer Mechanisms and Therapeutics) del que fue investigador principal José V. Bagán Sebastián (con una dotación de 287.707,4 euros para realizar la investigación que incluía también dos becarias Marie Curie que hicieron la tesis bajo su dirección -ambas con mención internacional- y realizado entre 2016-2020. Puesto: Investigador Principal.

– Proyecto competitivo a nivel nacional de la Convocatoria proyectos de investigación en salud, Instituto de Salud Carlos III, Subdirección General de Evaluación y Fomento de la Investigación del Ministerio de Ciencia, Innovación y Universidades (FIS), realizado entre 2019-2022. Dotación de 92.202 euros. Puesto: Investigador Principal.

– Proyecto competitivo a nivel nacional convocatoria del Ministerio de Ciencia e Innovación del apartado de Proyectos 10 – de Generación de conocimiento 2022. Concedido en julio de 2023 para iniciarse el 1 septiembre de 2023. Duración 3 años (2023-26). Dotación de 112.500 euros. Puesto: Investigador Principal.