Abstract
Simple SummaryIn this study, we investigated whether circulating microRNA expression levels and their potential diagnostic value are affected by cigarette smoking in lung cancer patients and healthy participants. Our findings support that cigarette smoking affects the reliable identification of circulating miRNAs as diagnostic biomarkers in lung cancer and suggest a smoking-dependent pathogenic role of miR-133a-3p in smokers.Cigarette smoking is a known risk factor for the development of lung cancer. We investigated whether circulating microRNA expression levels and their potential diagnostic value are affected by cigarette smoking in adenocarcinoma (AD) patients and healthy (H) participants. In total, 71 female AD patients and 91 H individuals were recruited, including 42 AD never-smokers (AD/CS−), 29 AD smokers (AD/CS+), 54 H never-smokers (H/CS−), and 37 H smokers (H/CS+). PCR array (754 microRNAs) and qPCR were performed on sera from the discovery and validation cohorts, respectively. The expression levels of miR-532-5p, miR-25-3p, and miR-133a-3p were significantly higher in adenocarcinoma patients than in healthy participants, independent of their smoking status. Multivariate analysis showed that levels of miR-133a-3p were independently associated with smoking. ROC analysis showed that only miR-532-5p discriminated AD patients from H controls (AUC: 0.745). However, when making comparisons according to cigarette smoking status, miR-532-5p discriminated AD/CS− patients from H/CS− controls with a higher AUC (AUC:0.762); miR-25-3p discriminated AD/CS+ patients from H/CS+ controls (AUC: 0.779), and miR-133a discriminated AD/CS+ patients from H/CS+ controls with the highest AUC of 0.935. Cancer and lung-cancer-enriched pathways were significantly associated with the three miRNAs; in addition, nicotinate/nicotinamide metabolism, inflammation, and pulmonary hypertension were associated with miR-133a-3p. Our findings highlight how cigarette smoking affects the reliable identification of circulating miRNAs as diagnostic biomarkers in lung cancer and suggest a smoking-dependent pathogenic role of miR-133a-3p in smokers.
Highlights
Lung cancer remains the leading cause of cancer-related deaths worldwide, with one of the lowest 5-year survival rates, 15–20% [1]
We investigated whether circulating microRNA expression levels and their potential diagnostic value are affected by cigarette smoking in lung cancer patients and healthy participants
There were no significant differences in age, body mass index (BMI), or obesity among the participants
Summary
Lung cancer remains the leading cause of cancer-related deaths worldwide, with one of the lowest 5-year survival rates, 15–20% [1]. MiRNAs participate in the epigenetic regulation of virtually all cellular processes studied under normal and disease conditions [5] They are detected in biological samples, such as tissue, peripheral blood, and other body fluids in a highly stable and quantifiable form, and their aberrant expressions have been associated with the presence of multiple cancers, including lung cancer [6,7,8]; miRNAs have a potential clinical value as diagnostic biomarkers. Despite the known association between cigarette smoking and lung cancer, little has been reported regarding the effect of smoking on the expression levels of circulating miRNAs in lung cancer and how it affects the identification of potential candidate miRNAs as non-invasive biomarkers of this disease. We searched for the potential biological relevance of smoking-related miRNAs in lung pathogenesis
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