Saé Muñiz-Hernández1, Sara Huerta-Yepez2, Norma Hernández-Pedro1, Laura-Alejandra Ramírez-Tirado3, Alejandro Aviles-Salas4, Altagracia Maldonado2, Daniel Hernández-Cueto2, Guillermina Baay-Guzmán2, Oscar Arrieta5,6. 1. Laboratory of Personalized Medicine, Instituto Nacional de Cancerología, Mexico City, Mexico. 2. Molecular Markers Laboratory, Hospital Infantil de México "Federico Gómez", Secretaría de Salud, Mexico City, Mexico. 3. Thoracic Oncology Unit, Instituto Nacional de Cancerología, San Fernando # 22, Tlalpan, 14080, Mexico City, Mexico. 4. Department of Pathology, Instituto Nacional de Cancerología, Mexico City, Mexico. 5. Laboratory of Personalized Medicine, Instituto Nacional de Cancerología, Mexico City, Mexico. ogar@unam.mx. 6. Thoracic Oncology Unit, Instituto Nacional de Cancerología, San Fernando # 22, Tlalpan, 14080, Mexico City, Mexico. ogar@unam.mx.
Abstract
BACKGROUND: Transcription factors such as retinoic acid receptor alpha (RARα) and beta (RARβ) and Yin Yang 1 (YY1) are associated with the progression of non-small cell lung cancer (NSCLC). In particular, a lack of RARβ expression is associated with NSCLC development. The aim of this study was to analyze the expression of RARα, RARβ and YY1 and their relationship with prognosis in patients with advanced NSCLC. METHODS: The expression of RARα, RARβ and YY1 was assessed by immunohistochemistry and quantitative computerized image software. RESULTS: Eighty-five patients treated with platinum-based chemotherapy were included in the analysis. The mean and standard deviation of the nuclear expression of RARα, RARβ and YY1 were 184.5 ± 124.4, 18 ± 27 and 16.6 ± 20.5, respectively. The nuclear expression of RARβ was associated with the nuclear expression of YY1 (R 2 = 0.28; p value < 0.0001). Patients with high nuclear expression of YY1 were likely to be non-smokers (61.9 vs 40.5 %). Median progression-free survival (PFS) was 5.9 months (3.48-8.28). Low expression of RARα was independently associated with worse PFS following chemotherapy (10.3 vs 5.46 months p = 0.040). Median overall survival (OS) was 15.6 months (4.5-26.7), and lower nuclear expression of RARβ was independently associated with shorter OS (27.5 vs 8.7 months; p = 0.037). CONCLUSION: Our study suggests that the loss of RARs is associated with a worse prognosis and these receptors could be a potential molecular target for NSCLC.
BACKGROUND: Transcription factors such as retinoic acid receptor alpha (RARα) and beta (RARβ) and Yin Yang 1 (YY1) are associated with the progression of non-small cell lung cancer (NSCLC). In particular, a lack of RARβ expression is associated with NSCLC development. The aim of this study was to analyze the expression of RARα, RARβ and YY1 and their relationship with prognosis in patients with advanced NSCLC. METHODS: The expression of RARα, RARβ and YY1 was assessed by immunohistochemistry and quantitative computerized image software. RESULTS: Eighty-five patients treated with platinum-based chemotherapy were included in the analysis. The mean and standard deviation of the nuclear expression of RARα, RARβ and YY1 were 184.5 ± 124.4, 18 ± 27 and 16.6 ± 20.5, respectively. The nuclear expression of RARβ was associated with the nuclear expression of YY1 (R 2 = 0.28; p value < 0.0001). Patients with high nuclear expression of YY1 were likely to be non-smokers (61.9 vs 40.5 %). Median progression-free survival (PFS) was 5.9 months (3.48-8.28). Low expression of RARα was independently associated with worse PFS following chemotherapy (10.3 vs 5.46 months p = 0.040). Median overall survival (OS) was 15.6 months (4.5-26.7), and lower nuclear expression of RARβ was independently associated with shorter OS (27.5 vs 8.7 months; p = 0.037). CONCLUSION: Our study suggests that the loss of RARs is associated with a worse prognosis and these receptors could be a potential molecular target for NSCLC.
Authors: Oscar Arrieta; Enrique Guzmán-de Alba; Luis Felipe Alba-López; Alicia Acosta-Espinoza; Jorge Alatorre-Alexander; José Francisco Alexander-Meza; Silvia Rosa Allende-Pérez; Salvador Alvarado-Aguilar; Margarita E Araujo-Navarrete; Luis Marcelo Argote-Greene; Cinthia Alejandra Aquino-Mendoza; Alma Magdalena Astorga-Ramos; Horacio Austudillo-de la Vega; Alejandro Avilés-Salas; Luis Javier Barajas-Figueroa; Nimbe Barroso-Quiroga; Mónica Blake-Cerda; Paula Anel Cabrera-Galeana; Germán Calderillo-Ruíz; Alma Delia Campos-Parra; Ana María Cano-Valdez; Daniel Capdeville-García; Graciano Castillo-Ortega; Catalina Casillas-Suárez; Patricia Castillo-González; José Francisco Corona-Cruz; María Elma Correa-Acevedo; Séfora Sonciry Cortez-Ramírez; Jhony Alberto de la Cruz-Vargas; Jaime G de la Garza-Salazar; María Dolores de la Mata-Moya; María Eugenia Domínguez-Flores; Hugo Ricardo Domínguez-Malagón; Luis Manuel Domínguez-Parra; Alfredo Domínguez-Peregrina; Jaime Durán-Alcocer; María Isabel Enríquez-Aceves; Abelardo Elizondo-Ríos; Moisés Dante Escobedo-Sánchez; Pablo Espinosa-Mireles de Villafranca; Alberto Flores-Cantisani; Juan Pablo Flores-Gutiérrez; Francisco Franco-Marina; Edwin Efraín Franco-González; Ramón Antonio Franco-Topete; Homero Fuentes-de la Peña; Susana Galicia-Amor; Dolores Gallardo-Rincón; Armando Gamboa-Domínguez; Jorge García-Andreu; Claudia María García-Cuéllar; María Cecilia García-Sancho-Figueroa; Rogelio García-Torrentera; Raquel Gerson-Cwilich; Arturo Gómez-González; León Green-Schneeweiss; María del Rocío Guillén-Núñez; Hilda Gutiérrez-Velázquez; Carlos Ibarra-Pérez; Edgardo Jiménez-Fuentes; Paula Juárez-Sánchez; Alejandro Juárez-Ramiro; Javier Kelly-García; Roberto Kuri-Exsome; Jesús Miguel Lázaro-León; Eucario León-Rodríguez; Sara Llanos-Osuna; Sara Llanos-Osuna; Ulises Loyola-García; José Sullivan López-González; Francisco Javier López y de Antuñano; Marco Antonio Loustaunau-Andrade; Eleazar Omar Macedo-Pérez; Limberth Machado-Villarroel; Manuel Magallanes-Maciel; Luis Martínez-Barrera; Jorge Martínez-Cedillo; Gloria Martínez-Martínez; Alfredo Medina-Esparza; Abelardo Meneses-García; Alejandro Mohar-Betancourt; Jaime Morales Blanhir; José Morales-Gómez; Daniel Motola-Kuba; Marcela Patricia Nájera-Cruz; Carolina del Carmen Núñez-Valencia; María Angélica Ocampo-Ocampo; María Dolores Ochoa-Vázquez; Carlos A Olivares-Torres; Andrés Palomar-Lever; Mario Patiño-Zarco; Rogelio Pérez-Padilla; Yolanda Rocío Peña-Alonso; Alfredo Rafael Pérez-Romo; Mario Aquilino Pérez; Paulo Martín Pinaya-Ruíz; María Adela Pointevin-Chacón; Juan José Poot-Braga; Rodolfo Posadas-Valay; Marcelino Ramirez-Márquez; Ivonne Reyes-Martínez; Julio Robledo-Pascual; Jerónimo Rodríguez-Cid; Carlos Enrique Rojas-Marín; Elizabeth Romero-Bielma; Jaime Ernesto Rubio-Gutiérrez; Julia Angelina Sáenz-Frías; Miguel Angel Salazar-Lezama; Karla Sánchez-Lara; Raúl Sansores Martínez; Patricio Santillán-Doherty; Juan Alejandro-Silva; José Luis Téllez-Becerra; Vinicio Toledo-Buenrostro; Luis Torre-Bouscoulet; Laura Torecillas-Torres; Marineé Torres; Víctor Tovar-Guzmán; Jenny Georgina Turcott-Chaparro; Jesús Javier Vázquez-Cortés; María Eugenia Vázquez-Manríquez; Natalia Vilches-Cisneros; José Felipe Villegas-Elizondo; Mauro M Zamboni; Jesús Zamora-Moreno; Juan W Zinser-Sierra Journal: Rev Invest Clin Date: 2013-03 Impact factor: 1.451
Authors: G V Scagliotti; F De Marinis; M Rinaldi; L Crinò; C Gridelli; S Ricci; E Matano; C Boni; M Marangolo; G Failla; G Altavilla; V Adamo; A Ceribelli; M Clerici; F Di Costanzo; L Frontini; M Tonato Journal: J Clin Oncol Date: 2002-11-01 Impact factor: 44.544
Authors: Hideto Ishii; Mark D Hulett; Jian-Mei Li; Fernando S Santiago; Christopher R Parish; Levon M Khachigian Journal: Int J Oncol Date: 2012-02-09 Impact factor: 5.650
Authors: Cherry Wongtrakool; Sarah Malpel; Julie Gorenstein; Jeff Sedita; Maria I Ramirez; T Michael Underhill; Wellington V Cardoso Journal: J Biol Chem Date: 2003-08-28 Impact factor: 5.157
Authors: Nitin Chakravarti; Reuben Lotan; Abdul H Diwan; Carla L Warneke; Marcella M Johnson; Victor G Prieto Journal: Clin Cancer Res Date: 2007-08-15 Impact factor: 12.531
Authors: Mayra Montecillo-Aguado; Belen Tirado-Rodriguez; Gabriela Antonio-Andres; Mario Morales-Martinez; Zhen Tong; Jun Yang; Bruce D Hammock; Rogelio Hernandez-Pando; Sara Huerta-Yepez Journal: Int J Mol Sci Date: 2022-05-31 Impact factor: 6.208
Authors: Hanna Drzewiecka; Donata Jarmołowska-Jurczyszyn; Andrzej Kluk; Bartłomiej Gałęcki; Wojciech Dyszkiewicz; Paweł P Jagodziński Journal: Int J Oncol Date: 2020-03-19 Impact factor: 5.650
Authors: Sara Huerta-Yepez; Ana Tirado-Rodriguez; Mayra R Montecillo-Aguado; Jun Yang; Bruce D Hammock; Oliver Hankinson Journal: Sci Rep Date: 2020-05-12 Impact factor: 4.379