Gene-expression profiles in lung adenocarcinomas related to chronic wood smoke or tobacco exposure.
BACKGROUND
Tobacco-smoke is the major etiological factor related to lung cancer. However, other important factor is chronic wood smoke exposure (WSE). Approximately 30 % of lung cancer patients in Mexico have a history of WSE, and present different clinical, pathological and molecular characteristics compared to tobacco related lung cancer, including differences in mutational profiles. There are several molecular alterations identified in WSE associated lung cancer, however most studies have focused on the analysis of changes in several pathogenesis related proteins.


METHODS
Our group evaluated gene expression profiles of primary lung adenocarcinoma, from patients with history of WSE or tobacco exposure. Differential expression between these two groups were studied through gene expression microarrays.


RESULTS
Results of the gene expression profiling revealed 57 statistically significant genes (p < 0.01). The associated biological functional pathways included: lipid metabolism, biochemistry of small molecules, molecular transport, cell morphology, function and maintenance. A highlight of our analysis is that three of the main functional networks represent 37 differentially expressed genes out of the 57 found. These hubs are related with ubiquitin C, GABA(A) receptor-associated like protein; and the PI3K/AKT and MEK/ERK signaling pathways.


CONCLUSIONS
Our results reflect the intrinsic biology that sustains the development of adenocarcinoma related to WSE and show that there is a different gene expression profile of WSE associated lung adenocarcinoma compared to tobacco exposure, suggesting that they arise through different carcinogenic mechanisms, which may explain the clinical and mutation profile divergences between both lung adenocarcinomas.
Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.|Translational Medicine Laboratory, INCan, Mexico City, Mexico.
Alette
A
Ortega-Gómez
Computational Genomics Department, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico. crangel@inmegen.gob.mx.
Claudia
C
Rangel-Escareño
Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.
Camilo
C
Molina-Romero
Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.
Eleazar Omar
EO
Macedo-Pérez
Department of Pathology, INCan, Mexico City, Mexico.
Alejandro
A
Avilés-Salas
Department of Radiotherapy, INCan, Mexico City, Mexico.
Alejandra
A
Lara-García
Computational Genomics Department, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico.
Gerardo
G
Alanis-Funes
Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.
Rubén
R
Rodríguez-Bautista
Cancer Genomics Laboratory, INMEGEN, Mexico City, Mexico.
Alfredo
A
Hidalgo-Miranda
Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico. ogar@unam.mx.|Postgraduate Unit, Faculty of Medicine, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico. ogar@unam.mx.
Oscar
O
Arrieta
D000230:Adenocarcinoma / Q000209:etiology / Q000378:metabolism*; D004781:Environmental Exposure; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology / Q000378:metabolism*; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D015995:Prevalence; D012307:Risk Factors; D053260:Soot / Q000506:poisoning*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D059467:Transcriptome; D014934:Wood / Q000009:adverse effects*
D009363:Neoplasm Proteins; D053260:Soot; D014028:Tobacco Smoke Pollution
Gene expression profiles; Microarray analysis; Non-small cell lung carcinoma ; Tobacco smoke; Wood smoke exposure