Cigarette smoke alters the transcriptome of non-involved lung tissue in lung adenocarcinoma patients

Abstract

Alterations in the gene expression of organs in contact with the environment may signal exposure to toxins. To identify genes in lung tissue whose expression levels are altered by cigarette smoking, we compared the transcriptomes of lung tissue between 118 ever smokers and 58 never smokers. In all cases, the tissue studied was non-involved lung tissue obtained at lobectomy from patients with lung adenocarcinoma. Of the 17,097 genes analyzed, 357 were differentially expressed between ever smokers and never smokers (FDR < 0.05), including 290 genes that were up-regulated and 67 down-regulated in ever smokers. For 85 genes, the absolute value of the fold change was ≥2. The gene with the smallest FDR was MYO1A (FDR = 6.9 × 10−4) while the gene with the largest difference between groups was FGG (fold change = 31.60). Overall, 100 of the genes identified in this study (38.6%) had previously been found to associate with smoking in at least one of four previously reported datasets of non-involved lung tissue. Seven genes (KMO, CD1A, SPINK5, TREM2, CYBB, DNASE2B, FGG) were differentially expressed between ever and never smokers in all five datasets, with concordant higher expression in ever smokers. Smoking-induced up-regulation of six of these genes was also observed in a transcription dataset from lung tissue of non-cancer patients. Among the three most significant gene networks, two are involved in immunity and inflammation and one in cell death. Overall, this study shows that the lung parenchyma transcriptome of smokers has altered gene expression and that these alterations are reproducible in different series of smokers across countries. Moreover, this study identified a seven-gene panel that reflects lung tissue exposure to cigarette smoke.

Biomarker potential of repetitive-element transcriptome in lung cancer

“…may explain the differences. Since it has been demonstrated that cigarette smoking alters the transcription level of many genes in normal lung cells of LUAD, although only seven genes up-regulated in all studies (Pintarelli et al, 2019), our results can extend the same conclusion to the RE transcriptome. Irrespective of the rationale for these differences, the 30 differentially expressed REs in normal cells cannot be considered lung biomarkers.…”

Analysis of genomic and transcriptomic variations as prognostic signature for lung adenocarcinoma

“…MGLL knock-out mice exhibited a higher incidence of neoplasia in lung [ 31 ]. MYO1A (Myosin I a) expression was higher in ever smokers than in never smokers [ 33 ]. MYO1A had mutations and promoter hypermethylation in patients with colorectal cancer and gastric tumors; therefore, lower levels of MYO1A expression was associated with faster tumor progress and poor prognosis [ 34 , 35 ].…”

Serum levels of retinol-binding protein 4 and the risk of non-small cell lung cancer

“…Proven by previous studies, the probability of NSCLC in long-term heavy smokers is 10–20 times higher than that in non-smokers, and the younger the age at which smokers begin to smoke, the higher the risk of NSCLC. [ 11 , 12 ] Furthermore, smoking not only directly affects personal health, but also has a negative impact on the health of the surrounding population, leading to a significant increase in the incidence of NSCLC among passive smokers. [ 13 , 14 ] The incidence of NSCLC in urban residents is higher than that in rural areas, which may be related to urban air pollution and the carcinogens contained in smoke and dust.…”