Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Biomarkers accurately distinguish mesothelioma from non-cancerous tissue

06.06.2014

Investigators pinpoint 4 key MicroRNAs, according to new report in the Journal of Molecular Diagnostics

Scientists have identified four biomarkers that may help resolve the difficult differential diagnosis between malignant pleural mesothelioma (MPM) and non-cancerous pleural tissue with reactive mesothelial proliferations (RMPs). This is a frequent differential diagnostic problem in pleural biopsy samples taken from patients with clinical suspicion of MPM. The ability to make more accurate diagnoses earlier may facilitate improved patient outcomes. This new study appears in the Journal of Molecular Diagnostics.

"Our goal was to identify microRNAs (miRNAs) that can aid in the differential diagnosis of MPM from RMPs," says lead investigator Eric Santoni-Rugiu, MD, PhD, of the Laboratory of Molecular Pathology at the Department of Pathology of Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. miRNAs, which are small, non-coding RNA strands composed of approximately 22 nucleotides, have been shown to be potential diagnostic, prognostic, and predictive markers in other cancers.

After screening 742 miRNAs, the investigators identified miR-126, miR-143, miR-145, and miR-652 as the best candidates to diagnose MPM. Using results from these four miRNAs, tissue samples from patients with known outcomes could be classified as MPM or non-cancerous with an accuracy of 0.94, sensitivity of 0.95, and specificity of 0.93. Further, an association between miRNA levels and patient survival could be made.

"The International Mesothelioma Interest Group (IMIG) recommends that a diagnostic marker of MPM have sensitivity/specificity of >0.80, and these criteria are fulfilled by our miRNA classifier," comments Dr. Santoni-Rugiu. The authors suggest that diagnostic accuracy can be further improved by adding immunohistochemical testing of miRNA targets in biopsy tissue to their miRNA assay. This combined assay could enable analysis of samples with low tumor cell count.

MPM, which is linked to long-term asbestos exposure, is an aggressive cancer originating from the mesothelial cells that line the membrane surrounding each lung, known as the pleura. Distinguishing MPM from noncancerous abnormalities, such as reactive mesothelial hyperplasia or fibrous pleurisy (organizing pleuritis), can be challenging as there are no generally accepted diagnostic biomarkers for differentiating these two conditions. As a result, patients often present with the disease when they are already at an advanced stage, and less than 20% of patients can be successfully treated surgically.

The current study, however, suggests that miRNAs may provide new opportunities for improving the accuracy of the differential diagnosis between MPM and noncancerous pleural conditions. If further validated, the combination of ISH for miRNAs with immunohistocemical testing of miRNA targets may therefore have the potential to aid in the diagnosis, and thus outcome, of MPM.

TECHNICAL DETAILS OF THE STUDY

To identify and assess microRNAs as possible diagnostic biomarkers of MPM, the expression of 742 miRNAs in FFPE preoperative diagnostic biopsies, surgically resected MPM specimens previously treated with chemotherapy, and corresponding non-neoplastic pleura (NNP) from five patients were screened using an RT-qPCR-based platform. Four miRNAs (miR-126, miR-143, miR-145, and miR-652) were significantly down-regulated (≥2 fold) in resected MPM and/or chemotherapy-naïve diagnostic tumor biopsies.

Validation of the obtained miRNA-expression profile was performed on surgically removed tissue samples from 40 MPM patients and 14 patient-matched NNP samples as well as 12 preoperative diagnostic biopsies and five non-neoplastic reactive-mesothelial proliferation due to pneumothorax. By performing binary logistic regression on the RT-qPCR data for the four miRNAs, the classifier differentiated MPM from NNP with high sensitivity and specificity. The classifier's optimal logit(P) value of 0.62 separated NNP and MPM samples with high sensitivity, specificity, and accuracy (all ≥0.93).

For immunohistochemistry, FFPE tissue sections underwent staining using antibodies to the known miR-126 targets LAT1 and Crk-II, were evaluated by light microscopy, and scored by a semiquantitative H score. Although no significant differences were found between MPM and NNP samples for Crk-II, the MPM samples had a median H score of 2 for LAT1 immunostaining, which was significantly higher than the 0.5 median score for the NNP samples (P < 0.01). Furthermore, the level of LAT1 in MPM inversely correlated with that of miR-126.

Eileen Leahy | Eurek Alert!
Further information:
http://www.elsevier.com

Further reports about: Molecular biomarkers biopsies diagnosis distinguish mesothelioma miR-126 miRNA miRNAs pleural sensitivity

More articles from Life Sciences:

nachricht Algorithms Offer Insight into Cellular Development
31.08.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cancer: Molecularly shutting down cancer cachexia
31.08.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Virtual Reality: 3D Human Body Reconstruction from Fraunhofer HHI digitizes Human Beings

Scientists at the Fraunhofer Institute for Telecommunications, Heinrich Hertz Institute, HHI have developed a method by which the realistic image of a person can be transmitted into a virtual world. The 3D Human Body Reconstruction Technology captures real persons with multiple cameras at the same time and creates naturally moving dynamic 3D models. At this year’s trade fairs IFA in Berlin (Hall 11.1, Booth 3) and IBC in Amsterdam (Hall 8, Booth B80) Fraunhofer HHI will show this new technology.

Fraunhofer HHI researchers have developed a camera system that films people with a perfect three-dimensional impression. The core of this system is a stereo...

Im Focus: Streamlining accelerated computing for industry

PyFR code combines high accuracy with flexibility to resolve unsteady turbulence problems

Scientists and engineers striving to create the next machine-age marvel--whether it be a more aerodynamic rocket, a faster race car, or a higher-efficiency jet...

Im Focus: X-ray optics on a chip

Waveguides are widely used for filtering, confining, guiding, coupling or splitting beams of visible light. However, creating waveguides that could do the same for X-rays has posed tremendous challenges in fabrication, so they are still only in an early stage of development.

In the latest issue of Acta Crystallographica Section A: Foundations and Advances , Sarah Hoffmann-Urlaub and Tim Salditt report the fabrication and testing of...

Im Focus: Piggyback battery for microchips: TU Graz researchers develop new battery concept

Electrochemists at TU Graz have managed to use monocrystalline semiconductor silicon as an active storage electrode in lithium batteries. This enables an integrated power supply to be made for microchips with a rechargeable battery.

Small electrical gadgets, such as mobile phones, tablets or notebooks, are indispensable accompaniments of everyday life. Integrated circuits in the interiors...

Im Focus: UCI physicists confirm possible discovery of fifth force of nature

Light particle could be key to understanding dark matter in universe

Recent findings indicating the possible discovery of a previously unknown subatomic particle may be evidence of a fifth fundamental force of nature, according...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

The energy transition is not possible without Geotechnics

25.08.2016 | Event News

New Ideas for the Shipping Industry

24.08.2016 | Event News

A week of excellence: 22 of the world’s best computer scientists and mathematicians in Heidelberg

12.08.2016 | Event News

 
Latest News

Cancer: Molecularly shutting down cancer cachexia

31.08.2016 | Life Sciences

Robust fuel cell heating unit developed

31.08.2016 | Power and Electrical Engineering

Algorithms Offer Insight into Cellular Development

31.08.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>