Gene-expression profiles in lung adenocarcinomas related to chronic wood smoke or tobacco exposure

Abstract

BackgroundTobacco-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.MethodsOur 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.ResultsResults 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.ConclusionOur 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.

Association between CD47 expression, clinical characteristics and prognosis in patients with advanced non‐small cell lung cancer

“…Chronic exposure to wood smoke is a common risk factor for lung cancer in Mexico and Latin American countries, 30 WSE affects the expression profiles of genes like EGFR, SMARCB1, ATM, and KDR, and also activates signaling pathways such as PIK3CA/AKT and MAPK. 30,31 It is known that WSE causes macrophage dysfunction and increases metalloproteinase activity, including MMP-2 and MMP-9, leading to cell invasion and migration. 32 Recently, Xu et al associated higher M1/M2-macrophage infiltration, adenocarcinoma histology and never smokers with CD47 expression in NSCLC tumor.…”

Targeted next generation sequencing identified a high frequency genetic mutated profile in wood smoke exposure-related lung adenocarcinoma patients

“…This is associated with the observed two-fold increase in lung cancer, particularly in nonsmoking Mexican women [ 15 ]. Previous reports have shown the association between WSE and lung cancer development mainly in women [ 7 , 8 , 13 ].…”

“…Exposure to carcinogenic compounds of wood smoke produce alterations in 53, phospho-TP53, and MDM2 expression increasing lung cancer risk [ 8 ]. Previously, our group reported a relation between WSE, female gender, EGFR mutations and different gene expression profiles [ 8 , 13 ]. Our population is a complex admixture of races and ethnic groups and difficult to characterize therefore we do not make distinctions according to races in our study.…”

“…Furthermore, it has been described that patients with WSE were associated with adenocarcinoma histology and higher incidence of EGFR mutations in up to 50% of the cases and low frequency of KRAS mutations with 6.7% [ 8 ]. Moreover, we reported gene expression profile of WSE-related NSCLC where 37 genes were significantly altered and closely related to UBC and GABARAPL1 affecting PI3K/AKT and MAPK pathways [ 13 ]. WSE is related to high levels of phosphorylated TP53, as well as promoter methylation in genes such as p16 and GATA4 [ 14 ].…”

Multi-omics Data Analyses Construct TME and Identify the Immune-Related Prognosis Signatures in Human LUAD

“…Many epidemiological investigations and experimental studies have attributed the occurrence and progression of LUAD largely to both environmental factors and genetic alterations. [2][3][4] Despite the increasing prevalence of health education and the decrease in smoking rates, the incidence trends have not changed considerably. A large number of never-smokers suffering from LUAD overturned the previous theory based only on environmental factors and refocused the researchers' attention on the in-depth alterations of genetic content.…”