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 Transport of molecular motors into cilia
28.03.2017 | Aarhus University

nachricht Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Transport of molecular motors into cilia

28.03.2017 | Life Sciences

A novel hybrid UAV that may change the way people operate drones

28.03.2017 | Information Technology

NASA spacecraft investigate clues in radiation belts

28.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>