Association between nuclear expression of retinoic acid receptor alpha and beta and clinicopathological features and prognosis of advanced non-small cell lung cancer.
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 (R2= 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).


CONCLUSIONS
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.
Laboratory of Personalized Medicine, Instituto Nacional de Cancerología, Mexico City, Mexico.
Saé
S
Muñiz-Hernández
Molecular Markers Laboratory, Hospital Infantil de México "Federico Gómez", Secretaría de Salud, Mexico City, Mexico.
Sara
S
Huerta-Yepez
Laboratory of Personalized Medicine, Instituto Nacional de Cancerología, Mexico City, Mexico.
Norma
N
Hernández-Pedro
Thoracic Oncology Unit, Instituto Nacional de Cancerología, San Fernando # 22, Tlalpan, 14080, Mexico City, Mexico.
Laura-Alejandra
LA
Ramírez-Tirado
Department of Pathology, Instituto Nacional de Cancerología, Mexico City, Mexico.
Alejandro
A
Aviles-Salas
Molecular Markers Laboratory, Hospital Infantil de México "Federico Gómez", Secretaría de Salud, Mexico City, Mexico.
Altagracia
A
Maldonado
Molecular Markers Laboratory, Hospital Infantil de México "Federico Gómez", Secretaría de Salud, Mexico City, Mexico.
Daniel
D
Hernández-Cueto
Molecular Markers Laboratory, Hospital Infantil de México "Federico Gómez", Secretaría de Salud, Mexico City, Mexico.
Guillermina
G
Baay-Guzmán
Laboratory of Personalized Medicine, Instituto Nacional de Cancerología, Mexico City, Mexico. ogar@unam.mx.|Thoracic Oncology Unit, Instituto Nacional de Cancerología, San Fernando # 22, Tlalpan, 14080, Mexico City, Mexico. ogar@unam.mx.
Oscar
O
Arrieta
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002945:Cisplatin / Q000627:therapeutic use*; D003936:Diagnosis, Computer-Assisted; D018572:Disease-Free Survival; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; C082925:retinoic acid receptor beta; D002945:Cisplatin
Biomarker; Non-small cell lung cancer; Platinum-based doublet chemotherapy; Retinoic acid receptor; YY1 transcription factor