Abstract
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.
Highlights
Malignant pleural mesothelioma (MPM) is an aggressive cancer of the pleura for which effective treatments are limited
To do so we focused on miR-625-3p, which we had been previously describing as a circulating biomarker in mesothelioma [13] and GAS5, a long non-coding RNA that we had functionally characterized in MPM [14]
We have investigated changes in the blood level of miR-625-3p and GAS5 before and after platinum chemotherapy in a unique cohort of MPM patients treated with neoadjuvant chemotherapy followed by extrapleural pneumonectomy (EPP) and randomized for radiotherapy [20]
Summary
Malignant pleural mesothelioma (MPM) is an aggressive cancer of the pleura for which effective treatments are limited. Efforts are ongoing to define objective and unbiased prognostic scores, which may help for the selection of candidate patients for surgery [4,5] These algorithms are mainly based on clinical characteristics and the biology of the tumor is only marginally taken into consideration, if at all. In our work we intended to perform an exploratory study to investigate the potential of ncRNA from the blood to help identify patients who will profit from surgery after platinum-based chemotherapy. We have investigated changes in the blood level of miR-625-3p and GAS5 before and after platinum chemotherapy in a unique cohort of MPM patients treated with neoadjuvant chemotherapy followed by extrapleural pneumonectomy (EPP) and randomized for radiotherapy [20]. Our work provides an exploratory observation on the prognostic role of miR-625-3p and GAS5 after adjuvant chemotherapy, which may represent an additional help for the selection of candidate patients for surgery
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