Proposing Specific Neuronal Epithelial-to-Mesenchymal Transition Genes as an Ancillary Tool for Differential Diagnosis among Pulmonary Neuroendocrine Neoplasms

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dc.contributor.authorPrieto, Tabatha Gutierrez
dc.contributor.authorBaldavira, Camila Machado
dc.contributor.authorMachado-Rugolo, Juliana [UNESP]
dc.contributor.authorOlivieri, Eloisa Helena Ribeiro
dc.contributor.authorda Silva, Eduardo Caetano Abilio
dc.contributor.authorAb’ Saber, Alexandre Muxfeldt
dc.contributor.authorTakagaki, Teresa Yae
dc.contributor.authorCapelozzi, Vera Luiza
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionAC Camargo Cancer Center
dc.contributor.institutionBarretos Cancer Hospital
dc.contributor.institutionFundação Oncocentro do Estado de São Paulo (FOSP)
dc.date.accessioned2023-07-29T14:00:15Z
dc.date.available2023-07-29T14:00:15Z
dc.date.issued2022-12-01
dc.description.abstractPulmonary neuroendocrine neoplasms (PNENs) are currently classified into four major histotypes, including typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell lung carcinoma (SCLC). This classification was designed to be applied to surgical specimens mostly anchored in morphological parameters, resulting in considerable overlapping among PNENs, which may result in important challenges for clinicians’ decisions in the case of small biopsies. Since PNENs originate from the neuroectodermic cells, epithelial-to-mesenchymal transition (EMT) gene expression shows promise as biomarkers involved in the genotypic transformation of neuroectodermic cells, including mutation burden with the involvement of chromatin remodeling genes, apoptosis, and mitosis rate, leading to modification in final cellular phenotype. In this situation, additional markers also applicable to biopsy specimens, which correlate PNENs subtypes with systemic treatment response, are much needed, and current potential candidates are neurogenic EMT genes. This study investigated EMT genes expression and its association with PNENs histotypes in tumor tissues from 24 patients with PNENs. PCR Array System for 84 EMT-related genes selected 15 differentially expressed genes among the PNENs, allowing to discriminate TC from AC, LCNEC from AC, and SCLC from AC. Functional enrichment analysis of the EMT genes differentially expressed among PNENs subtypes showed that they are involved in cellular proliferation, extracellular matrix degradation, regulation of cell apoptosis, oncogenesis, and tumor cell invasion. Interestingly, four EMT genes (MAP1B, SNAI2, MMP2, WNT5A) are also involved in neurological diseases, in brain metastasis, and interact with platinum-based chemotherapy and tyrosine–kinase inhibitors. Collectively, these findings emerge as an important ancillary tool to improve the strategies of histologic diagnosis in PNENs and unveil the four EMT genes that can play an important role in driving chemical response in PNENs.en
dc.description.affiliationLaboratory of Genomics and Histomorphometry Department of Pathology University of São Paulo Medical School (USP), SP
dc.description.affiliationHealth Technology Assessment Center (NATS) Clinical Hospital (HCFMB) Medical School of São Paulo State University (UNESP), SP
dc.description.affiliationInternational Center of Research/CIPE AC Camargo Cancer Center, SP
dc.description.affiliationMolecular Oncology Research Center Barretos Cancer Hospital, SP
dc.description.affiliationFundação Oncocentro do Estado de São Paulo (FOSP), SP
dc.description.affiliationDivision of Pneumology Instituto do Coração (Incor) Medical School of University of São Paulo, SP
dc.description.affiliationUnespHealth Technology Assessment Center (NATS) Clinical Hospital (HCFMB) Medical School of São Paulo State University (UNESP), SP
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIdCNPq: 303735/2021-0
dc.identifierhttp://dx.doi.org/10.3390/genes13122309
dc.identifier.citationGenes, v. 13, n. 12, 2022.
dc.identifier.doi10.3390/genes13122309
dc.identifier.issn2073-4425
dc.identifier.scopus2-s2.0-85144527857
dc.identifier.urihttp://hdl.handle.net/11449/249019
dc.language.isoeng
dc.relation.ispartofGenes
dc.sourceScopus
dc.subjectdiagnosis
dc.subjectepithelial-to-mesenchymal transition
dc.subjectmetastasis
dc.subjectmorphology
dc.subjectpulmonary neuroendocrine neoplasms
dc.titleProposing Specific Neuronal Epithelial-to-Mesenchymal Transition Genes as an Ancillary Tool for Differential Diagnosis among Pulmonary Neuroendocrine Neoplasmsen
dc.typeArtigo
unesp.author.orcid0000-0002-5364-7305[2]
unesp.author.orcid0000-0003-3984-4959[3]
unesp.author.orcid0000-0003-2277-2100[7]
unesp.author.orcid0000-0001-9732-5853[8]

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