A recently publish research from the Journal of Molecular Diagnostics has revealed the role played by four major MicroRNAs. The researchers have discovered four biomarkers that can aid in simplifying the challenging task of performing a differential diagnosis between the non-cancerous pleural tissue with reactive proliferation (RMPs) and malignant pleural mesothelioma (MPM). This research will prove to be a ground-breaking innovation.

This is a widely occurring challenge that doctors encounter in making a differential diagnostic in pleural biopsy samples that are obtained from patients who are clinically suspected to harbour malignant pleural mesothelioma. This new study that has been published in the Journal of Molecular Diagnostics have provided ground-breaking insight that will assist experts in performing much more accurate diagnosis, which will also improve the outcomes of the treatments.

According to Eric Santoni-Rugiu, the lead research at the Laboratory of Molecular Pathology at the Department of Pathology of Rigshospitalet, at the Copenhagen University Hospital, Denmark, the goal of this study was to discover the microRNAs that can help in performing an accurate differential diagnosis of RMPs from MPM.

These microRNAs are very tiny, non-coding RNA strands that contain around 22 nucleotides, and scientific research reveals that they are diagnostic, prognostic and predictive markers in various kinds of cancers.

Mesothelioma Cancer Claims
National Cancer Institute (NCI)

The researchers conducted this study by screening 742 microRNAs, and the results identified miR-126, miR-143, miR-145, and miR-652 as the best markers to diagnose a patient with malignant pleural mesothelioma. After obtaining results from all four of these microRNAs, the researchers tend classified the tissue samples they had obtained from patients with known outcomes as non-cancerous pleural tissue or malignant pleural mesothelioma with an impressive accuracy of 0.94, specificity of 0.93, and sensitivity of 0.95. Moreover, a link was established between the survival chances of a patient and his/her miRNA levels.

Dr Santoni-Rugui explained that the International Mesothelioma Interest Group (IMIG) advises that the diagnostic marker for malignant pleural mesothelioma have a sensitivity and specificity of less than 0.80, the miRNA classifier used in the study fulfilled this criteria. The researchers explain that experts can bring about further improvements in the diagnostic accuracy by performing additional immunohistochemical testing of the miRNA targets within the biopsy tissue in their miRNA assay. The addition of this testing with allow the analysis of samples that harbour a low count of tumour cells.

Malignant pleural mesothelioma is associated to extreme exposure towards asbestos for a long duration of time, which is basically an extremely hazardous and aggressive kind of cancer that is triggered from within the mesothelial cells found within the pleura, a membrane that surrounds both of our lungs.

It is extremely difficult for doctors to differentiate malignant pleural mesothelioma from non-cancerous disorders and abnormalities, for instance, fibrous pleurisy or organising pleuritis, and reactive mesothelial hyperplasia, amongst others, since there are no validated and universally accepted diagnostic biomarkers that can aid in distinguishing these two ailments. This is why most patients get their condition diagnosed when it has reached an advanced and aggressive stage, and statistics reveal that only less than 20% patients with this condition are successfully cured after a surgical treatment.

This particular research sheds light on this challenge by explaining that miRNAs are capable of opening up new alternatives and options to bring about marked improvements in making an accurate differential diagnosis between noncancerous pleural conditions and malignant pleural mesothelioma. If researchers test and validate the legitimacy of this study with further research, the combination of immunohistochemical testing of miRNA targets, accompanied with ISH for miRNAs can have the potential of improving the diagnostic accuracy and treatment outcomes for patients suffering from malignant pleural mesothelioma.

Technicalities highlighted in the Research

In order to discover and examine the microRNAs as potential diagnostic biomarkers to identify and treat malignant pleural mesothelioma, the researchers obtained 742 miRNAs amongst FFPE preoperative diagnostic biopsies, along with surgically resected specimens of malignant pleural mesothelioma that previously underwent treatment with chemotherapy, and corresponding non-neoplastic pleura was obtained from five patients, and screen with the help of an RT-qPCR based platform.

The researchers noted that four miRNAs: miR-126, mirR-143, miR-145 and miR-652, were majorly down-regulated in patients with resected malignant pleural mesothelioma, or diagnostic tumour biopsies that were completely naïve towards chemotherapy.

Mesothelioma Non-Cancerous Tissue
American Urological Association

The researchers validated their deducted miRNA-express profile by performing on surgically eliminated tissue samples that were obtained from 40 patients suffering from malignant pleural mesothelioma, while obtaining 14 patient-match samples of NNP, along with 12 preoperative diagnostic biopsies, and five non-neoplastic reactive-mesothelial proliferation that occurred because of pneumothorax.

After conducting the binary logistic regression upon the RT-qPCR statistics obtained from the four miRNAs, the classifier highlighted the differences between malignant pleural mesothelioma and noncancerous pleural by specificity and high sensitivity.

While examining the potential of immunohistochemistry, the FFPE tissue sections were exposed to a staining process that used antibodies to the identified miR-126 targets LAT1 and Crk-II, which were examined using light microscopy, and assigned a semi-quantitative H score.

Even though the researchers failed to highlight a major factor to distinguish malignant pleural mesothelioma with noncancerous pleural, the samples with MPM achieved a median H score of 2 for LAT1 immunostaining, and it turned out to be much higher when compared with the score of NNP samples, which was 0.5. Moreover, the level of LAT1 in malignant pleural mesothelioma had an inverse correlation with the level of LAT1 in miR-126.


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