Navigation Links
Biomarkers accurately distinguish mesothelioma from non-cancerous tissue
Date:6/5/2014

Philadelphia, PA, June 6, 2014 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-nave 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.


'/>"/>

Contact: Eileen Leahy
jmdmedia@elsevier.com
732-238-3628
Elsevier Health Sciences
Source:Eurekalert

Related biology news :

1. Shrink wrap used to enhance detection of infectious disease biomarkers
2. Global Cancer Biomarkers Market 2012-2016 with Agilent Technologies Inc., Gen-Probe Inc. and Astellas Pharma US Inc. Dominating
3. Novel method could help bring cancer biomarkers to clinic
4. Regulus Demonstrates Initial Progress in microRNA Biomarkers MS Collaboration and Receives Milestone Payment from Biogen Idec
5. Use of Biomarkers in Clinical Trials for Drugs Outside of Oncology is Increasing
6. Droplet Digital PCR enables reproducible quantification of microRNA biomarkers
7. Biomarkers Market: Epigenetic & MicroRNA Biomarkers Report
8. Novel biomarkers improve diagnosis in rheumatoid arthritis
9. Epigenetic biomarkers may predict if a specific diet and exercise regimen will work
10. New AAN/ALS Association Clinical Fellow Will Pursue Immune Biomarkers
11. NIH funds research to identify Parkinsons biomarkers
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/14/2017)... June 15, 2017  IBM (NYSE: IBM ) is introducing ... event dedicated to developing collaboration between startups and global businesses, ... 15-17. During the event, nine startups will showcase the solutions ... various industries. France ... market, with a 30 percent increase in the number of ...
(Date:5/16/2017)... 16, 2017  Veratad Technologies, LLC ( www.veratad.com ), ... and identity verification solutions, announced today they will participate ... May 15 thru May 17, 2017, in ... Trade Center. Identity impacts the lives ... today,s quickly evolving digital world, defining identity is critical ...
(Date:5/6/2017)... 5, 2017 RAM Group , ... new breakthrough in biometric authentication based on a ... properties to perform biometric authentication. These new sensors are ... created by Ram Group and its partners. This sensor ... supply chains and security. Ram Group is a ...
Breaking Biology News(10 mins):
(Date:9/21/2017)... , ... September 21, 2017 , ... ... office, which includes executive, engineering and manufacturing functions to The LaunchPort™ Accelerator at ... Factory™, provide a full range of manufacturing and business services to its Residents. ...
(Date:9/21/2017)... (PRWEB) , ... September 21, 2017 , ... ... clinical client portal. Each relaunch of the portal includes new features that facilitate ... medical device companies seek to remain at the forefront of medical advancements, they ...
(Date:9/21/2017)... , ... September 21, 2017 , ... ... neon green this month, the response was swift and efficient thanks to the ... ). RRWQG is made up of more than 50 stakeholders, including officials from ...
(Date:9/20/2017)... ... September 20, 2017 , ... ... with Koch Agronomic Services (Koch) to feature new innovations aimed at helping farmers ... first quarter 2018. American Farmer airs Tuesdays at 8:30aET on RFD-TV. Check your ...
Breaking Biology Technology: