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

Our plain-English summary of 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, by J. Kresoja-Rakic, A. Szpechcinski, M.B. Kirschner, et al (Non-coding RNA, 2019).

The study

• Authors: J. Kresoja-Rakic, A. Szpechcinski, M.B. Kirschner, M. Ronner, B. Minatel, V.D. Martinez, W.L. Lam, W. Weder, R. Stahel, M. Früh, F. Cerciello, E. Felley-Bosco
• Journal: Non-coding RNA
• Published: 2019;5(2)
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This exploratory laboratory study asked whether blood levels of two non-coding RNA molecules, miR-625-3p and GAS5, changed after chemotherapy in people with malignant pleural mesothelioma, and whether the changes were linked to outcome. It did not study asbestos exposure. Blood was taken before and after platinum-based chemotherapy from 36 patients in the SAKK 17/04 trial. These patients were treated with chemotherapy followed by extrapleural pneumonectomy. After samples were excluded for RNA degradation or hemolysis, paired samples from 32 patients were analysed. Neither molecule's change on its own differed significantly between the 8 patients whose disease progressed and the 24 with partial response or stable disease. A rise in miR-625-3p combined with a fall in GAS5 was significantly associated with progression (p = 0.0393). Patients whose GAS5 fell had a median overall survival of 7.8 months, versus 11.8 months when it rose (p = 0.0308), and shorter progression-free survival (p = 0.0096). miR-625-3p was not significantly linked to survival. The authors concluded these markers may help treatment decisions. They noted the small number of patients and the need for larger validation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Exploratory biomarker study using blood samples from patients in a clinical trial, measured before and after chemotherapy
• Who was studied: 36 malignant pleural mesothelioma patients enrolled in the SAKK 17/04 trial (NCT00334594): 29 epithelioid, 2 sarcomatoid, 4 mixed and 1 spindle cell shaped; 33 male and 3 female; mean age 62.4. The protocol was approved by the Ethics Committee of the Zurich University Hospital. After exclusions, paired samples from 32 patients were analysed. Dates of collection are not given.
• Exposure: Asbestos exposure was not studied. The factor studied was the change in plasma levels of miR-625-3p and the long non-coding RNA GAS5 after platinum-based neo-adjuvant chemotherapy.
• Main results:
  • After two samples were excluded for RNA degradation and two for hemolysis, 32 pairs of plasma samples remained for analysis.
  • miR-625-3p levels showed a bimodal distribution, with 16 patients in a low group and 16 in a high group. Cloning and sequencing of the test product found only miR-625-3p and its variant forms (isomiRs).
  • After chemotherapy, GAS5 levels decreased in 9 patients, increased in 22 and did not change in one.
  • The cohort included 24 patients with partial response or stable disease and 8 with progressive disease after chemotherapy.
  • Change in miR-625-3p alone did not differ significantly between the progressive disease group and the partial response/stable disease group (p = 0.6851). Change in GAS5 alone also did not differ significantly between these groups (p = 0.1845).
  • The combination of increased miR-625-3p and decreased GAS5 after chemotherapy was significantly associated with disease progression (Fisher's test, p = 0.0393).
  • Patients with decreased GAS5 after chemotherapy had a median overall survival of 7.8 months, compared with 11.8 months for patients with increased GAS5 (p = 0.0308).
  • Progression-free survival was significantly shorter for patients with decreased GAS5 after chemotherapy (p = 0.0096).
  • There were no significant differences in overall or progression-free survival between patients with low and high miR-625-3p levels.
  • Small RNA sequencing data from 87 mesothelioma tissue samples from The Cancer Genome Atlas confirmed that the miR-625-3p isomiRs found in blood were present in tumour tissue.
• The authors' conclusion: The authors concluded that changes in circulating miR-625-3p and GAS5 were associated with response to platinum-based chemotherapy and predicted outcome after neo-adjuvant treatment and surgery. They stated that these blood-based markers may be helpful for clinical treatment decisions in malignant pleural mesothelioma.
• Limitations the authors state:
  • The observations are based on a limited number of patients.
  • The findings need validation in an independent clinical study with a larger number of samples.
  • The bimodal distribution of miR-625-3p was not seen in a previous study and may be linked to the detection method used.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Chemotherapy, Disease Progression, Progression-Free Survival.

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