Low miR-150-5p and miR-320b Expression Predicts Reduced Survival of COPD Patients

Andreas Keller, Nicole Ludwig, Tobias Fehlmann, Mustafa Kahraman, Christina Backes, Fabian Kern, Claus F Vogelmeier, Caroline Diener, Ulrike Fischer, Frank Biertz, Christian Herr, Rudolf A Jörres, Hans-Peter Lenhof, Robert Bals, Eckart Meese, Andreas Keller, Nicole Ludwig, Tobias Fehlmann, Mustafa Kahraman, Christina Backes, Fabian Kern, Claus F Vogelmeier, Caroline Diener, Ulrike Fischer, Frank Biertz, Christian Herr, Rudolf A Jörres, Hans-Peter Lenhof, Robert Bals, Eckart Meese

Abstract

Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of death, reducing life expectancy on average between 5 and 7 years. The survival time after diagnosis, however, varies considerably as a result of the heterogeneity of COPD. Therefore, markers that predict individual survival of COPD patients are of great value. We analyzed baseline molecular profiles and collected 54 months of follow-up data of the cohort study "COPD and SYstemic consequences-COmorbidities NETwork" (COSYCONET). Genome-wide microRNA signatures from whole blood collected at time of the inclusion in the study were generated for 533 COPD patients including patients that deceased during the 54-month follow-up period (n = 53) and patients that survived this period (n = 480). We identified two blood-born microRNAs (miR-150-5p and miR-320b) that were highly predictive for survival of COPD patients. The expression change was then confirmed by RT-qPCR in 245 individuals. Ninety percent of patients with highest expression of miR-150-5p survived the 54-month period in contrast to only 50% of patients with lowest expression intensity. Moreover, the abundance of the oncogenic miR-150-5p in blood of COPD patients was predictive for the development of cancer. Thus, molecular profiles measured at the time of a COPD diagnosis have a high predictive power for the survival of patients.

Keywords: COPD; cancer; miRNA; survival.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Overview of the study set up. The study consists of three parts: (1) a primary microarray-based screening, (2) a bioinformatics evaluation of the data and candidate selection, and (3) a validation in a subset of samples using RT-qPCR. Blood-born microRNA profiles were related to the survival of patients with chronic obstructive pulmonary disease (COPD) over a period of 54 months after diagnosis. COSYCONET: COPD and SYstemic consequences-COmorbidities NETwork.
Figure 2
Figure 2
Volcano plot for the differentially expressed miRNAs in COPD patients surviving a 54-month period versus patients who died within this period. Significant miRNAs are indicated in red (overexpressed in surviving patients) or green (reduced expression in surviving patients).
Figure 3
Figure 3
Kaplan-Meier analyses of blood-born miRNA pattern determined by array analysis. (A) MiR-320b indicates longer survival of COPD patients who show higher abundance of miR-320b. (B) MiR-21-5p indicates longer survival of COPD patients who show lower abundance of miR-21-5p.
Figure 4
Figure 4
Kaplan-Meier analyses of blood-born miRNA patterns determined by RT-qPCR. (A) MiR-320b indicates longer survival of COPD patients who show higher abundance of miR-320b. (B) MiR-150-5p indicates longer survival of COPD patients who show higher abundance of miR-150-5p. (C) Splitting the patients in tertile groups with high, medium, and low expression of miR-150-5p showed longest survival for patients with highest expression. (D) Splitting in quintile groups also demonstrated the longest survival for patients with highest expression.

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