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miR-625-3p and lncRNA GAS5 in Liquid Biopsies for Predicting the Outcome of Malignant Pleural Mesothelioma Patients Treated with Neo-Adjuvant Chemotherapy and Surgery

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Laboratory of Molecular Oncology, Department of Thoracic Surgery, University Hospital Zürich, 8091 Zürich, Switzerland
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Department of Thoracic Surgery, University Hospital Zürich, 8091 Zürich, Switzerland
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BC Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada
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IWK Health Centre, Halifax, NS B3K 6R8, Canada
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Comprehensive Cancer Center Zürich, University Hospital Zürich, 8091 Zürich, Switzerland
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Cantonal Hospital of St. Gallen, 9007 St. Gallen, Switzerland
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Department of Medical Oncology/Hematology, University of Bern, CH-3000 Bern, Switzerland
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Clinic of Oncology, University Hospital Zürich, 8091 Zürich, Switzerland
*
Authors to whom correspondence should be addressed.
Present address: Department of Genetics and Clinical Immunology, National Research Institute of Tuberculosis and Lung Diseases, 26 Plocka St., 01-138 Warsaw, Poland.
Present address: Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Non-Coding RNA 2019, 5(2), 41; https://doi.org/10.3390/ncrna5020041
Received: 15 May 2019 / Revised: 14 June 2019 / Accepted: 15 June 2019 / Published: 17 June 2019
(This article belongs to the Special Issue Regulatory Non-Coding RNAs in Oncogenesis and Tumor Inhibition)
Combining neo-adjuvant chemotherapy and surgery is part of multimodality treatment of malignant pleural mesothelioma (MPM), but not all patients benefit from this approach. In this exploratory analysis, we investigated the prognostic value of circulating miR-625-3p and lncRNA GAS5 after neo-adjuvant chemotherapy. 36 MPM patients from the SAKK 17/04 trial (NCT00334594), whose blood was available before and after chemotherapy were investigated. RNA was isolated from plasma and reverse transcribed into cDNA. miR-16-5p and β-actin were used as a reference gene for miR-625-3p and GAS5, respectively. After exclusion of samples due to hemolysis or RNA degradation, paired plasma samples from 32 patients before and after chemotherapy were further analyzed. Quantification of miR-625-3p levels in all 64 samples revealed a bimodal distribution and cloning and sequencing of miR-625-3p qPCR product revealed the presence of miR-625-3p isomiRs. Relative change of the circulating miR-625-3p and GAS5 levels after chemotherapy showed that increased circulating miR-625-3p and decreased GAS5 was significantly associated with disease progression (Fisher’s test, p = 0.0393). In addition, decreased levels of circulating GAS5 were significantly associated with shorter overall and progression-free survival. Our exploratory analysis revealed a potential value of circulating non-coding RNA for selection of patients likely to benefit from surgery after platinum-based adjuvant chemotherapy. View Full-Text
Keywords: circulating noncoding RNA; miR-625-3p isomiRs; GAS5; malignant pleural mesothelioma; liquid biopsy circulating noncoding RNA; miR-625-3p isomiRs; GAS5; malignant pleural mesothelioma; liquid biopsy
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Kresoja-Rakic, J.; Szpechcinski, A.; Kirschner, M.B.; Ronner, M.; Minatel, B.; Martinez, V.D.; Lam, W.L.; Weder, W.; Stahel, R.; Früh, M.; Cerciello, F.; Felley-Bosco, E. miR-625-3p and lncRNA GAS5 in Liquid Biopsies for Predicting the Outcome of Malignant Pleural Mesothelioma Patients Treated with Neo-Adjuvant Chemotherapy and Surgery. Non-Coding RNA 2019, 5, 41.

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