The Fibrosis-Targeted Collagen/Integrins Gene Profile Predicts Risk of Metastasis in Pulmonary Neuroendocrine Neoplasms

Autor(es)

Prieto, Tabatha Gutierrez ^[1] ; Machado-Rugolo, Juliana ^{[1, 2]} ; Baldavira, Camila Machado ^[1] ; Velosa, Ana Paula Pereira ^[3] ; Teodoro, Walcy Rosolia ^[3] ; Ab Sabe, Alexandre Muxfeldt ^[1] ; Capelozzi, Vera Luiza ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med USP, Dept Pathol, Lab Genom & Histomorphometry, Sao Paulo - Brazil

^[2] Sao Paulo State Univ UNESP, Sch Med, Clin Hosp HCFMB, Hlth Technol Assessment Ctr NATS, Botucatu, SP - Brazil

^[3] Univ Sao Paulo, Sch Med USP, Clin Hosp, Div Rheumatol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN ONCOLOGY; v. 11, AUG 11 2021.
• Citações Web of Science: 0

Resumo

Recently, collagen/integrin genes have shown promise as predictors of metastasis mainly in non-small cell lung cancer and breast cancer. However, it is unknown if these gene expression profiling differ in metastatic potential of pulmonary neuroendocrine neoplasms (PNENs). In this study, we sought to identify differentially expressed collagen/integrin genes in PNENs in order to understand the molecular mechanisms underlying the development of stroma-associated fibrosis for invasion and metastasis. We compared collagen/integrin gene expression profiling between PNE tumors (PNETs) and PNE carcinomas (PNECs) using a two-stage design. First, we used PCR Array System for 84 ECM-related genes, and among them, we found COL1A2, COL3A1, COL5A2, ITGA5, ITGAV, and ITGB1 functionally involved in the formation of the stroma-associated fibrosis among PNENs histological subtypes. Second, we examined the clinical association between the six collagen/integrin genes in tumor tissues from 24 patients with surgically excised PNENs. However, the pathological exam of their resected tissues demonstrated that 10 developed lymph node metastasis and 7 distant metastasis. We demonstrated and validated up regulation of the six fibrogenic genes in PNECs and down regulation in PNETs that were significantly associated with metastasis-free and overall survival (P<0.05). Our study implicates up regulation of fibrogenic genes as a critical molecular event leading to lymph node and distant metastasis in PNENs. (AU)

• Processo FAPESP: 18/20403-6 - Marcadores biomoleculares de proliferação e remodelamento em doenças respiratórias agudas e crônicas: promissores alvos terapêuticos
• Beneficiário: Vera Luiza Capelozzi
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/12151-0 - Avaliação da expressão proteica de DLL-3 e ASCL-1 como nova perspectiva em biomarcadores para o diagnóstico precoce dos carcinomas pulmonares de pequenas células
• Beneficiário: Tabatha Gutierrez Prieto Martins Rocha
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado