Genome-Wide MicroRNA Expression Profiles in COPD: Early Predictors for Cancer Development

Abstract

Chronic obstructive pulmonary disease (COPD) significantly increases the risk of developing cancer. Biomarker studies frequently follow a case-control set-up in which patients diagnosed with a disease are compared to controls. Longitudinal cohort studies such as the COPD-centered German COPD and SYstemic consequences-COmorbidities NETwork (COSYCONET) study provide the patient and biomaterial base for discovering predictive molecular markers. We asked whether microRNA (miRNA) profiles in blood collected from COPD patients prior to a tumor diagnosis could support an early diagnosis of tumor development independent of the tumor type. From 2741 participants of COSYCONET diagnosed with COPD, we selected 534 individuals including 33 patients who developed cancer during the follow-up period of 54 months and 501 patients who did not develop cancer, but had similar age, gender and smoking history. Genome-wide miRNA profiles were generated and evaluated using machine learning techniques. For patients developing cancer we identified nine miRNAs with significantly decreased abundance (two-tailed unpaired t-test adjusted for multiple testing P < 0.05), including members of the miR-320 family. The identified miRNAs regulate different cancer-related pathways including the MAPK pathway (P = 2.3 × 10−5). We also observed the impact of confounding factors on the generated miRNA profiles, underlining the value of our matched analysis. For selected miRNAs, qRT-PCR analysis was applied to validate the results. In conclusion, we identified several miRNAs in blood of COPD patients, which could serve as candidates for biomarkers to help identify COPD patients at risk of developing cancer.

Differential expression of matrix metalloproteinases and miRNAs in the metastasis of oral squamous cell carcinoma

“…Moreover, qRT-PCR confirmed that the expression of miR-7109-5p and miR-34b was significantly downregulated in metastatic OSCC samples compared with nonmetastatic tumour samples using samples collected from another cohort of OSCC patients. The abnormal expression of miR-7109-5p has been reported to occur in breast cancer and is associated with cancer development in patients with chronic obstructive pulmonary disease [37,38]. The reduced expression of miR-34b and miR-129-3p was observed in gastric cancers due to DNA hypermethylation and was associated with poor clinicopathological features [39].…”

miRNA sequencing reveals miRNA‐4508 from peripheral blood lymphocytes as potential diagnostic biomarker for silica‐related pulmonary fibrosis: A multistage study

“…miRNA are considered biomarkers of a wide range of lung diseases. For instance, downregulation of miRNA‐339‐5p and upregulation of miRNA‐21 in plasma may act as early predictors of lung adenocarcinoma, whereas miRNA‐320 family members (miRNA‐320e and miRNA‐320c) were identified as candidate biomarkers for identifying patients with chronic obstructive pulmonary disease (COPD) who are at a risk of developing cancer . Meanwhile, Yang et al .…”

Neoantigens in Chronic Obstructive Pulmonary Disease and Lung Cancer: A Point of View

“…COPD and lung cancer are heterogeneous diseases that are for a large part (85% [man] and 69% [female] for instance in the Dutch situation [2018]) linked causatively by the use of cigarettes (Dutch national institute for public health and the environment; http://www.jellinek.nl). In Table , the global situation and the situation in the continents is presented. From this table, one can notice that in the developed world (Europe, Oceania, and North America) similar ratios of mortality for COPD and lung cancer can be observed.…”

“…The risk of developing lung cancer is eight times higher if COPD has been diagnosed . Common molecular mechanisms related to inflammation, to innate immune responses and to carcinogenic processes are affected in COPD and lung cancer .…”