hsa-miR-29c\* is linked to the prognosis of malignant pleural mesothelioma

Our plain-English summary of hsa-miR-29c* is linked to the prognosis of malignant pleural mesothelioma, by H.I. Pass, C. Goparaju, S. Ivanov, et al (Cancer Research, 2010).

The study

• Authors: H.I. Pass, C. Goparaju, S. Ivanov, J. Donington, M. Carbone, M. Hoshen, D. Cohen, A. Chajut, S. Rosenwald, H. Dan, S. Benjamin, R. Aharonov
• Journal: Cancer Research
• Published: 2010;70(5):1916-24
• Cited by: 116 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The inability to forecast outcomes for malignant mesothelioma prevents clinicians from providing aggressive multimodality therapy to the most appropriate individuals who may benefit from such an approach. We investigated whether specific microRNAs (miR) could segregate a largely surgically treated group of mesotheliomas into good or bad prognosis categories. A training set of 44 and a test set of 98 mesothelioma tumors were analyzed by a custom miR platform, along with 9 mesothelioma cell lines and 3 normal mesothelial lines. Functional implications as well as downstream targets of potential prognostic miRs were investigated. In both the training and test sets, hsa-miR-29c* was an independent prognostic factor for time to progression as well as survival after surgical cytoreduction. The miR was expressed at higher levels in epithelial mesothelioma, and the level of this miR could segregate patients with this histology into groups with differing prognosis. Increased expression of hsa-miR-29c* predicted a more favorable prognosis, and overexpression of the miR in mesothelioma cell lines resulted in significantly decreased proliferation, migration, invasion, and colony formation. Moreover, major epigenetic regulation of mesothelioma is mediated by hsa-miR-29c* and was shown through downregulation of DNA methyltransferases as well as upregulation of demethylating genes. A single miR has the potential to be a prognostic biomarker in mesothelioma, and validation of these findings as well as investigation of its downstream targets may give insight for potential therapies in the future.

In plain English

This study asked whether the level of a small RNA molecule called hsa-miR-29c* in tumor tissue was linked to how patients did after surgery for malignant pleural mesothelioma. The authors tested surgical tumor specimens collected from 1990 to 2005. Of 142 specimens, 129 passed quality checks, forming a training set of 37 and a test set of 92. In the training set, patients with higher hsa-miR-29c* had a longer median time until the cancer progressed (14 versus 4 months) and longer median survival (32 versus 8 months). Using the same cutoff in the test set, median survival was 21.6 versus 9.1 months. Stage, hsa-miR-29c* level and lymph node status were independent predictors of survival. Levels did not differ significantly between 24 patients without asbestos exposure and exposed patients. A survival difference between these two groups (27 versus 13 months) was not statistically significant. Higher hsa-miR-29c* went with longer survival in both groups. In two mesothelioma cell lines, adding the molecule reduced cell growth, migration and invasion. The authors concluded it was the sole candidate prognostic microRNA in their study and said the findings need validation in other patient groups.

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: Laboratory study of archived surgical tumor specimens (microRNA microarray profiling with a training set and a test set, plus qRT-PCR validation), combined with cell-line experiments
• Who was studied: 142 snap-frozen malignant pleural mesothelioma surgical specimens collected from 1990 to 2005. Of these, 129 passed quality assurance (37 of 44 in the training set, 92 of 98 in the test set). Follow-up was current as of September 2008. Most patients had cytoreductive surgery (34 of 37 in the training set, 83 of 92 in the test set).
• Exposure: The main factor studied was tumor expression of the microRNA hsa-miR-29c*. Asbestos exposure history (exposed versus not exposed) was also compared. No fiber types, jobs or doses are given, and the article does not describe how exposure was determined.
• Main results:
  • Training set: using the median hsa-miR-29c* expression (8.8) as a cutoff, the low- and high-expression groups had median time to progression of 4 months versus 14 months (P = 0.0002). Higher expression was associated with longer time to progression.
  • Training set: the low- and high-expression groups had median survival of 8 months versus 32 months (P = 0.000019).
  • Test set, using the training-set cutoff of 8.8: median time to progression was 5.5 months versus 12.8 months (P = 0.008).
  • Test set, using the same cutoff: median survival was 9.1 months versus 21.6 months (P = 0.0026).
  • Test set: hsa-miR-29c* was higher in epithelial tumors (fold change 2.63; P = 0.0005). Among epithelial mesotheliomas, it separated a group with median survival of 21.6 months from one with 9.1 months (P = 0.00046).
  • In a multivariate (Cox) analysis of the test set, stage, hsa-miR-29c* expression and lymph node status were independent predictors of survival; gender and histologic type were not. The same three factors remained the only independent predictors when all 129 patients were analyzed.
  • In 16 samples tested by qRT-PCR, the PCR cutoff divided patients into groups with median survivals of 4.2 months versus more than 10 years (P = 0.02).
  • Among all 129 patients, mean hsa-miR-29c* expression in the 24 patients without asbestos exposure (9.2) was not significantly different from that in exposed patients (8.7). The trend toward longer survival in unexposed patients (median 27 versus 13 months) was not significant (P = 0.11).
  • Higher hsa-miR-29c* was associated with significantly longer survival both in asbestos-exposed patients (20 versus 9 months) and in unexposed patients (31 versus 11 months).
  • In mesothelioma cell lines H2595 and HP1, adding hsa-miR-29c* was associated with decreased proliferation and migration, a significant decrease in invasion, and significantly inhibited colony formation. It also decreased expression of the DNA methyltransferase DNMT3A.
• The authors' conclusion: The authors concluded that hsa-miR-29c* was the only microRNA that was prognostic in both the training and test sets and on both measurement methods, making it the sole candidate prognostic microRNA in their investigations of malignant pleural mesothelioma.
• Limitations the authors state:
  • The authors stated that the findings must be validated in other surgical cohorts and in patients treated without surgery.
  • The authors stated that the asbestos-related findings need validation in larger cohorts with precise asbestos exposure information or lung fiber analysis.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Prognosis, Pleural Mesothelioma, Mesothelioma, Multimodal Therapy, Cytoreductive Surgery, Histology, Biomarker.

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