Association of MiR-126 with soluble mesothelin-related peptides, a marker for malignant mesothelioma

Our plain-English summary of Association of MiR-126 with soluble mesothelin-related peptides, a marker for malignant mesothelioma, by L. Santarelli, E. Strafella, S. Staffolani, et al (PloS One, 2011).

The study

• Authors: L. Santarelli, E. Strafella, S. Staffolani, M. Amati, M. Emanuelli, D. Sartini, V. Pozzi, D. Carbonari, M. Bracci, E. Pignotti, P. Mazzanti, A. Sabbatini, R. Ranaldi, S. Gasparini, J. Neuzil, M. Tomasetti
• Journal: PloS One
• Published: 2011;6(4):e18232
• Cited by: 87 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Improved detection methods for diagnosis of malignant pleural mesothelioma (MPM) are essential for early and reliable detection as well as treatment. Since recent data point to abnormal levels of microRNAs (miRNAs) in tumors, we hypothesized that a profile of deregulated miRNAs may be a marker of MPM and that the levels of specific miRNAs may be used for monitoring its progress.

Methods And Results: miRNAs isolated from fresh-frozen biopsies of MPM patients were tested for the expression of 88 types of miRNA involved in cancerogenesis. Most of the tested miRNAs were downregulated in the malignant tissues compared with the normal tissues. Of eight significantly downregulated, three miRNAs were assayed in cancerous tissue and adjacent non-cancerous tissue sample pairs collected from 27 formalin-fixed, paraffin-embedded MPM tissues by quantitative RT-PCR. Among the miRNAs tested, only miR-126 significantly remained downregulated in the malignant tissues. Furthermore, the performance of the selected miR-126 as biomarker was evaluated in serum samples of asbestos-exposed subjects and MPM patients and compared with controls. MiR-126 was not affected by asbestos exposure, whereas it was found strongly associated with VEGF serum levels. Levels of miR-126 in serum, and its levels in patients' serum in association with a specific marker of MPM, SMRPs, correlate with subjects at high risk to develop MPM.

Conclusions And Significance: We propose miR-126, in association with SMRPs, as a marker for early detection of MPM. The identification of tumor biomarkers used alone or, in particular, in combination could greatly facilitate the surveillance procedure for cohorts of subjects exposed to asbestos.

In plain English

This Italian laboratory study looked for small RNA molecules (microRNAs) that might help detect malignant pleural mesothelioma (MPM). The authors first measured 88 cancer-related microRNAs in fresh biopsies from 10 MPM patients, compared with pooled microRNAs from 5 normal mesothelial tissues. Most were lower in the tumors, and eight were significantly lower. Three of these were then measured in 27 stored MPM tumors, each paired with nearby non-cancerous tissue. Only miR-126 (70%, 54–85%, p = 0.024) and, less so, miR-32 (65%, 50–80%, p = 0.050) separated tumor from normal tissue on the area under the ROC curve, which the text calls accuracy. Serum miR-126 was then measured in 196 asbestos-exposed people, 44 MPM patients and 50 healthy controls without occupational asbestos exposure. Only serum VEGF, a blood-vessel growth factor, correlated strongly with miR-126. Exposure duration, cumulative fiber dose and asbestos-related disease did not. A miR-126 cut-off separated exposed people from controls with 60% sensitivity and 74% specificity. The authors proposed miR-126, together with the blood marker SMRPs, as a marker for early detection of MPM. The participants' asbestos fiber types were not stated.

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 biomarker study: microRNA measurement in tumor versus normal tissue, followed by comparison of serum levels in asbestos-exposed subjects, MPM patients and healthy controls
• Who was studied: Fresh biopsies from 10 MPM patients and 5 subjects with normal mesothelium. Stored (formalin-fixed, paraffin-embedded) tissue from 27 MPM patients with adjacent non-cancerous tissue. Serum from three groups: 196 asbestos-exposed subjects (188 males, 8 females; enrolled November 2004 to April 2010 at the Institute of Occupational Medicine, Polytechnic University of Marche, Ancona, Italy), 44 MPM patients, and 50 healthy controls never occupationally exposed to asbestos.
• Exposure: Occupational asbestos exposure, fiber type not specified. Exposed subjects had been exposed for an average of 23.3 years (plus or minus 10.7), with a cumulative fiber dose of 28.8 (plus or minus 50.4) fibers per cubic centimetre times years. Evidence of asbestos-related disease (fibrosis and pleural plaques) was found in 56 of 196 (29%).
• Main results:
  • In fresh biopsies, most of the 88 microRNAs tested were lower in MPM tissue than in pooled normal control samples.
  • For the 27 tissue pairs, the figure legend states that the measure of how well each microRNA separated cancerous from non-malignant tissue was the area under the ROC curve (AUC). The results text calls this measure 'accuracy'.
  • In the 27 paired MPM and adjacent non-malignant tissue samples, miR-126 had a reported accuracy of 70% (54–85%, p = 0.024).
  • In the same 27 pairs, miR-32 had a reported accuracy of 65% (50–80%, p = 0.050).
  • In the same 27 pairs, miR-335 lost its significance (accuracy 42%, 26–58%, p = 0.312).
  • All three microRNAs were more reduced in advanced-stage (S2) tumors than in early-stage tumors, but this did not reach statistical significance.
  • The serum analysis looked at asbestos-related diseases, exposure duration, cumulative fiber dose, VEGF and SMRPs. Of these, only VEGF levels strongly correlated with miR-126 (R = 0.659, p = 0.02).
  • MPM patients had higher serum VEGF and SMRP levels than asbestos-exposed subjects and controls.
  • A serum miR-126 cut-off distinguished asbestos-exposed subjects from controls with sensitivity 60% and specificity 74%.
  • A serum miR-126 cut-off distinguished asbestos-exposed subjects from MPM patients with sensitivity 73% and specificity 74%.
  • Serum SMRP levels correlated with serum miR-126. The estimated probability of developing the disease was higher when decreasing miR-126 occurred together with increasing SMRPs.
• The authors' conclusion: The authors proposed miR-126, in association with SMRPs, as a marker for early detection of MPM.

Topics

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

Medical terms in this study, explained in our Lexicon: Soluble Mesothelin-Related Peptides (SMRP), Malignant Mesothelioma, Pleural Mesothelioma, Biomarker, Asbestos Exposure.

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