Identification of miRNA-103 in the Cellular Fraction of Human Peripheral Blood as a Potential Biomarker for Malignant Mesothelioma – A Pilot Study

Abstract

BackgroundTo date, no biomarkers with reasonable sensitivity and specificity for the early detection of malignant mesothelioma have been described. The use of microRNAs (miRNAs) as minimally-invasive biomarkers has opened new opportunities for the diagnosis of cancer, primarily because they exhibit tumor-specific expression profiles and have been commonly observed in blood of both cancer patients and healthy controls. The aim of this pilot study was to identify miRNAs in the cellular fraction of human peripheral blood as potential novel biomarkers for the detection of malignant mesothelioma.Methodology/Principal FindingsUsing oligonucleotide microarrays for biomarker identification the miRNA levels in the cellular fraction of human peripheral blood of mesothelioma patients and asbestos-exposed controls were analyzed. Using a threefold expression change in combination with a significance level of p<0.05, miR-103 was identified as a potential biomarker for malignant mesothelioma. Quantitative real-time PCR (qRT-PCR) was used for validation of miR-103 in 23 malignant mesothelioma patients, 17 asbestos-exposed controls, and 25 controls from the general population. For discrimination of mesothelioma patients from asbestos-exposed controls a sensitivity of 83% and a specificity of 71% were calculated, and for discrimination of mesothelioma patients from the general population a sensitivity of 78% and a specificity of 76%.Conclusions/SignificanceThe results of this pilot study show that miR-103 is characterized by a promising sensitivity and specificity and might be a potential minimally-invasive biomarker for the diagnosis of mesothelioma. In addition, our results support the concept of using the cellular fraction of human blood for biomarker discovery. However, for early detection of malignant mesothelioma the feasibility of miR-103 alone or in combination with other biomarkers needs to be analyzed in a prospective study.

Malignant mesothelioma as an oxidative stress-induced cancer: An update

“…More importantly, they found that miRNA-126 can be used in combination with another reported MM biomarker, soluble mesothelin-related 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 peptides (SMRPs) to predict the risk of an asbestos-exposed population to develop MM [139]. More recently, Weber and coworkers reported the circulating level of miRNA-103 as another potential MM diagnostic marker [140].…”

Biomarkers in the prevention and follow-up of workers exposed to asbestos

“…Bononi et al in 2016 proposed three circulating up-regulated microRNAs, i.e., miR-197-3p, miR-1281 and miR-32-3p as potential new MPM biomarkers (58). Weber et al (59) found that the combination of circulating miR-132-3p with miR-126 improved the diagnostic performance of MPM, while miR-20b, miR-28-3p, and miR-146b-5p showed no statistically significant differences between asbestosexposed controls and mesothelioma patients. De Santi et al confirmed, after a strong validation test, a significant differentially expression of miR-185, miR-197 and miR-299 in MPM cases and identified a two-miRNA prognostic signature, composed by Let-7c-5p and miR-151a-5p (60).…”

Diagnostic and prognostic biomarkers for malignant mesothelioma: an update

“…Several groups explored the miRNA expression profiles in MM tissues using microarrays (90)(91)(92)(93)(94)(95). An initial analysis of miRNAs expression in MM (94) reported 12 miRNAs overexpressed and 9 miRNAs down-regulated in MM tissues compared with normal tissues.…”