New biomarkers and therapeutics can be discovered during COPD-lung cancer transition

Abstract

Chronic obstructive pulmonary disease (COPD) has been found to be associated with lung cancer regardless of a patient's smoking history. Of 11,888 incident cases of lung cancer, 23 % had a prior diagnosis of COPD compared with only 6 % of the 37,605 controls (Powell et al. 2013). The prevalence of COPD in lung cancer patients varies from 8 to 50 %, and the annual incidence of lung cancer arising from COPD is 0.8-1.2 %. This indicates that ∼1 % of COPD patients develop lung cancer each year, while only 0.2 % of patients with normal pulmonary function develop lung cancer. The Environment and Genetics in a Lung Cancer Etiology population-based case-control study showed that lung cancer risk was increased among individuals with chronic bronchitis, emphysema, and COPD (Sekine et al. 2012). COPD co-exists with 40-70 % of lung cancer patients, and 50 % of newly diagnosed lung cancer patients had COPD whereas only 8 % of smokers without lung cancer had COPD. Smokers with COPD are more susceptible to lung cancer.Epidemiological studies indicate that tobacco smoke exposure accounts for nearly 90 % of cases of COPD and lung cancer. However, genetic factors may explain why 10-30 % of smokers develop to COPD, even though genetic network and gene set enrichment in cigarette smoking were found to be correlated with the development of lung cancer (Fang et al. 2013). COPD is closely linked to susceptibility to lung cancer and acts as the most important risk factor for lung cancer among smokers, predating lung cancer in up to 80 % of cases. Genome-wide association studies on lung cancer, lung function, and COPD have identified a number of overlapping Bsusceptibility^loci. With stringent phenotyping, several overlapping loci are independently associated with both COPD and lung cancer, but with pulmonary inflammation and apoptotic processes mediated by the bronchial epithelium (Bondarczuk and PiotrowskaSeget 2013;Corbel et al. 2002;Bao et al. 2016a). Some lung cancer-specific genetic variants were identified as BCOPD-related^genetic variants associated with clinical variables (Young et al. 2011).Gene and protein expression profiles were initially investigated among patients with stable COPD, acute exacerbation of COPD (AECOPD), COPD with or without smoking, and COPD with or without lung cancer, to compare with those of healthy or health smokers (Chen et al. 2012). A number of disease-, stage-, duration-, or therapy-specific biomarkers were selected to screen susceptible populations of COPD or lung cancer. Using clinical bioinformatic techniques, the specificity, biological function, or prevalence of selected target genes or proteins from patients with AECOPD were furthermore validated in association with different types, survival rate, or potential mechanism of lung cancer (Ye et al. 2015). Chronic inflammation associated with COPD likely plays a role in the pathogenesis of lung cancer, and acute exacerbation can be the critical factor in the tumorigenesis of lung cancer. Inflammation

Myocyte enhancer factor 2D provides a cross-talk between chronic inflammation and lung cancer

“…Further data mining showed significantly higher MEF2D level in COPD patients with NSCLC than that in smokers, patients with COPD and no NSCLC, or patients with NSCLC and no COPD. Growing evidence has shown that patients with chronic respiratory conditions such as COPD exhibit a significantly higher risk of lung cancer [8]. It is reported that 50–90% lung cancer patients have coexisting COPD [20].…”

“…Patients with chronic respiratory diseases are predisposed to higher incidence of lung cancer [2–7]. Chronic obstructive pulmonary disease (COPD), a chronic inflammatory lung disease, is closely related to susceptibility to lung cancer and stands as the most important risk factor of lung cancer among smokers [8]. Patients with moderate-to-severe COPD have a fivefold higher risk of developing lung cancer than smokers without the disease [9].…”

Inhibitory effects of Actinidia Chinensis planch root extracts (acRoots) on human lung cancer cells through retinoic acid receptor beta

“…Another question is whether acRoots-induced down-regulation of RARB is acRoots inhibition-specific or a general reaction of the compensation, since we found that LPS could also induce the down-regulation of RARB gene. It is also critical to validate the repeatability and stability of RARB-interacted elements in metabolism-associated network as efficacy-specific biomarkers and druggable targets [21][22][23][24][25][26].…”

Can single-cell RNA sequencing crack the mystery of cells?

“…Single-cell measurements were used to evaluate the DNA-damaging ability of the herbicide in freshly isolated human leukocytes (Villarini et al 2000) or the ethoxyresorufin-Odeethylase activity of cytochrome P450 1A1 in singleliving cells with the microspectrofluorometric technique (Taira et al 2007). The measurements of single-cell biology and sequencing are recently considered as an important approach to investigate molecular mechanisms of drug efficacy and resistances, discovery and development of therapeutic targets, and genealogic phenotypes of cells during disease progression (Chu et al 2017;Wang 2016;Wang et al 2017). Single-cell sequencing is an important measure to define intercellular heterogeneity, rare cell types, cell genealogies, somatic mosaicism, microbes, and disease evolution, including single-cell DNA genome sequencing, DNA methylome sequencing, and RNA sequencing.…”