Two Lung Cancer Development-Related Genes, Forkhead Box M1 (FOXM1) and Apolipoprotein E (APOE), are overexpressed in Bronchial of Patients after Long-Term Exposure to Sulfur Mustard

Document Type: Research article


Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.


Sulfur mustard (SM) is a strong alkylating and mutagenic compound that targets human
airway system. We considered the expression of Forkhead box M1 (FOXM1) and apolipoprotein
E (APOE) genes, which are responsible for cell proliferation, differentiation, tumorigenesis,
and increased risk of lung cancer, in the lung bronchial tissue of patients exposed to SM.
After performing pulmonary functional tests (PFTs), 11 human subjects (five controls and six
SM-exposed patients) were entered in this study. Total RNA were extracted from all biopsy
samples and then cDNA was synthesised for each specimen using RT-PCR. Changes in gene
expression were measured using a RT2 Profiler ™PCR Array. PFTs have demonstrated more
obstructive and restrictive spirometric patterns among patients compared to the controls. A
higher expression was recorded for both examined genes in bronchial of SM-exposed patients.
Expression of FOXM1 and APOE genes in bronchial of the patients was significantly (p <
0.001) overexpressed by 14.8316 and 3.9504-folds, respectively. Mustard lungs were associated
with increased expression of FOXM1 and APOE genes, which suggests an increased risk of
lung cancer among these patients. Since FOXM1 and APOE are considered as oxidative stress
responsive genes, we speculate that increased expression of these genes is more likely linked to
overproduction of reactive oxygen species (ROS) and oxidative stress (OS) in mustard lungs.
Further studies are required at protein level among SM-exposed patients with lung cancer to
use these genes as lung cancer biomarkers among these patients.


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