Clinical significance of circulating miR-126 quantification in malignant mesothelioma patients

Our plain-English summary of Clinical significance of circulating miR-126 quantification in malignant mesothelioma patients, by M. Tomasetti, S. Staffolani, L. Nocchi, et al (Clinical Biochemistry, 2012).

The study

• Authors: M. Tomasetti, S. Staffolani, L. Nocchi, J. Neuzil, E. Strafella, N. Manzella, L. Mariotti, M. Bracci, M. Valentino, M. Amati, L. Santarelli
• Journal: Clinical Biochemistry
• Published: 2012;45(7-8):575-81
• Cited by: 87 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: Aim of this study was to evaluate the accuracy and precision of the detection of individual miRNA as clinical biomarkers in the serum.

Design And Methods: miRNA-126 was quantified in serum using endogenous and exogenous controls for normalization and the accuracy and precision of the method evaluated. The diagnostic value of serum miRNA-126 was evaluated in malignant mesothelioma (MM) and non-small-cell lung cancer (NSCLC) patients using both relative and absolute qRT-PCR methods.

Results: The use of endogenous invariant and exogenous synthetic controls as well sample dilution markedly improves the accuracy and precision of the assay. The inter- and intra-assay analyses revealed that relative qRT-PCR is a more reliable method. Circulating miR-126 detected in the serum by relative qRT-PCRs was found low-expressed in both malignancies, significantly differentiated MM patients from healthy controls and NSCLC from MM, but do not discriminate NSCLC patients from control subjects. Kaplan-Meier analysis revealed that low level of circulating miR-126 in MM patients was strongly associated with worse prognosis.

Conclusions: We propose that this approach can be adopted for accurate analysis of other suitable circulating miRNA markers of different types of cancer.

Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

In plain English

This laboratory study from the University Hospital of Ancona, Italy, tested ways of measuring a small RNA molecule, miR-126, in blood serum. It then checked whether miR-126 could tell malignant mesothelioma apart from non-small-cell lung cancer and from healthy people. The article does not report the subjects' asbestos exposure. Using serum from one volunteer, the authors found that combining two reference controls and diluting the serum reduced measurement variation. With diluted serum and both controls, the relative method's variation was 3% within a day and 5% between days, while the absolute method stayed more variable (26–36%). They then tested serum from 45 mesothelioma patients, 20 lung cancer patients and 56 healthy controls. miR-126 was low in both cancers and lowest in mesothelioma. It significantly separated mesothelioma patients from controls (p=0.001) and from lung cancer patients (p=0.003). It did not significantly separate lung cancer patients from controls (p=0.07). Among mesothelioma patients, low miR-126 was associated with worse prognosis (p=0.03). The authors concluded that miR-126 lacks specificity, because low levels occur in other tumours, and suggested using it alongside markers such as mesothelin.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory method-validation study of a serum biomarker, followed by a comparison of patients with healthy controls and a survival analysis
• Who was studied: 45 malignant mesothelioma patients (31 men, 14 women, mean age 67.7) and 20 non-small-cell lung cancer patients recruited at the Oncology Clinic of the University Hospital of Ancona, Italy, from November 2007 to December 2011. The comparison group was 56 healthy controls undergoing screening radiography. Serum from one 28-year-old non-smoking female volunteer was used for the precision tests.
• Main results:
  • Relative method, undiluted control serum: within-day variation was 16–17% with either single reference control. Using both controls together reduced it to 6%.
  • Relative method, diluted control serum: within-day variation fell below 5% (3% in Table 1B) when both reference controls were used.
  • Relative method, both controls: between-day variation was 8% for undiluted and 5% for diluted control serum.
  • Absolute method: variation was high in undiluted control serum (39–44%) and fell to 26–36% after 10-fold dilution.
  • miR-126 levels were low in both mesothelioma and non-small-cell lung cancer patients compared with healthy controls. They were lower in mesothelioma patients than in lung cancer patients.
  • miR-126 significantly distinguished mesothelioma patients from healthy controls (p=0.001) and from lung cancer patients (p=0.003).
  • The difference between lung cancer patients and healthy controls was not statistically significant (p=0.07).
  • Among the mesothelioma patients, low circulating miR-126 was associated with worse prognosis (log-rank p=0.03).
• The authors' conclusion: The authors concluded that miR-126 may be used clinically for mesothelioma in combination with other cancer-specific markers, such as mesothelin.
• Limitations the authors state:
  • The authors stated that miR-126 lacks specificity, because low serum levels are also found in other tumours.
  • The authors noted unclear reference ranges and a lack of large-sample data for miRNA cancer markers.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Biomarker, Lung Cancer, Prognosis.

Related studies

• Combined circulating epigenetic markers to improve mesothelin performance in the diagnosis of malignant mesothelioma — L. Santarelli, S. Staffolani, et al. (2015)
• Association of MiR-126 with soluble mesothelin-related peptides, a marker for malignant mesothelioma — L. Santarelli, E. Strafella, et al. (2011)
• Four-miRNA Signature to Identify Asbestos-Related Lung Malignancies — L. Santarelli, S. Gaetani, et al. (2019)
• Are circulating microRNAs suitable for the early detection of malignant mesothelioma? Results from a nested case-control study — D.G. Weber, A. Brik, et al. (2019)
• Clinical evaluation of circulating miR-548a-3p and -20a expression in malignant pleural mesothelioma patients — M. Matboli, A.E. Shafei, et al. (2018)
• Mechanism of miR-222 and miR-126 regulation and its role in asbestos-induced malignancy — S. Gaetani, F. Monaco, et al. (2020)

Browse return to medical research.