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 More detailed analysis of how cells react to stress
08.02.2016 | Universität Zürich

nachricht A new potential biomarker for cancer imaging
05.02.2016 | Universiti Putra Malaysia (UPM)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: From allergens to anodes: Pollen derived battery electrodes

Pollens, the bane of allergy sufferers, could represent a boon for battery makers: Recent research has suggested their potential use as anodes in lithium-ion batteries.

"Our findings have demonstrated that renewable pollens could produce carbon architectures for anode applications in energy storage devices," said Vilas Pol, an...

Im Focus: Automated driving: Steering without limits

OmniSteer project to increase automobiles’ urban maneuverability begins with a € 3.4 million budget

Automobiles increase the mobility of their users. However, their maneuverability is pushed to the limit by cramped inner city conditions. Those who need to...

Im Focus: Microscopy: Nine at one blow

Advance in biomedical imaging: The University of Würzburg's Biocenter has enhanced fluorescence microscopy to label and visualise up to nine different cell structures simultaneously.

Fluorescence microscopy allows researchers to visualise biomolecules in cells. They label the molecules using fluorescent probes, excite them with light and...

Im Focus: NASA's ICESat-2 equipped with unique 3-D manufactured part

NASA's follow-on to the successful ICESat mission will employ a never-before-flown technique for determining the topography of ice sheets and the thickness of sea ice, but that won't be the only first for this mission.

Slated for launch in 2018, NASA's Ice, Cloud and land Elevation Satellite-2 (ICESat-2) also will carry a 3-D printed part made of polyetherketoneketone (PEKK),...

Im Focus: Sinking islands: Does the rise of sea level endanger the Takuu Atoll in the Pacific?

In the last decades, sea level has been rising continuously – about 3.3 mm per year. For reef islands such as the Maldives or the Marshall Islands a sinister picture is being painted evoking the demise of the island states and their cultures. Are the effects of sea-level rise already noticeable on reef islands? Scientists from the ZMT have now answered this question for the Takuu Atoll, a group of Pacific islands, located northeast of Papua New Guinea.

In the last decades, sea level has been rising continuously – about 3.3 mm per year. For reef islands such as the Maldives or the Marshall Islands a sinister...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

AKL’16: Experience Laser Technology Live in Europe´s Largest Laser Application Center!

02.02.2016 | Event News

From intelligent knee braces to anti-theft backpacks

26.01.2016 | Event News

DATE 2016 Highlighting Automotive and Secure Systems

26.01.2016 | Event News

 
Latest News

Ocean acidification makes coralline algae less robust

08.02.2016 | Earth Sciences

Online shopping might not be as green as we thought

08.02.2016 | Studies and Analyses

Proteomics and precision medicine

08.02.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>