MicroRNA signature of malignant mesothelioma with potential diagnostic and prognostic implications

Our plain-English summary of MicroRNA signature of malignant mesothelioma with potential diagnostic and prognostic implications, by S. Busacca, S. Germano, L. De Cecco, et al (American Journal of Respiratory Cell and Molecular Biology, 2010).

The study

• Authors: S. Busacca, S. Germano, L. De Cecco, M. Rinaldi, F. Comoglio, F. Favero, B. Murer, L. Mutti, M. Pierotti, G. Gaudino
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 2010;42(3):312-9
• Cited by: 132 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

MicroRNAs (miRNAs) post-transcriptionally regulate the expression of target genes, and may behave as oncogenes or tumor suppressors. Human malignant mesothelioma is an asbestos-related cancer, with poor prognosis and low median survival. Here we report, for the first time, a cross-evaluation of miRNA expression in mesothelioma (MPP-89, REN) and human mesothelial cells (HMC-telomerase reverse transcriptase). Microarray profiling, confirmed by real-time quantitative RT-PCR, revealed a differential expression of miRNAs between mesothelioma and mesothelial cells. In addition, a computational analysis combining miRNA and gene expression profiles allowed the accurate prediction of genes potentially targeted by dysregulated miRNAs. Several predicted genes belong to terms of Gene Ontology (GO) that are associated with the development and progression of mesothelioma. This suggests that miRNAs may be key players in mesothelioma oncogenesis. We further investigated miRNA expression on a panel of 24 mesothelioma specimens, representative of the three histotypes (epithelioid, biphasic, and sarcomatoid), by quantitative RT-PCR. The expression of miR-17-5p, miR-21, miR-29a, miR-30c, miR-30e-5p, miR-106a, and miR-143 was significantly associated with the histopathological subtypes. Notably, the reduced expression of two miRNAs (miR-17-5p and miR-30c) correlated with better survival of patients with sarcomatoid subtype. Our preliminary analysis points at miRNAs as potential diagnostic and prognostic markers of mesothelioma, and suggests novel tools for the therapy of this malignancy.

In plain English

This laboratory study compared microRNAs (small molecules that help control which genes are active) in two mesothelioma cell lines, MPP-89 and REN, with non-tumor human mesothelial cells called HMC-TERT. It did not measure anyone's asbestos exposure. Across three repeat experiments, the authors found 65 microRNAs whose levels differed. Both mesothelioma lines shared 10 raised and 19 lowered microRNAs compared with the non-tumor cells. Combining these results with gene activity data and computer predictions identified 587 genes as possible targets of these microRNAs. The authors then measured 10 microRNAs in 24 untreated tumor specimens from a hospital near Venice, Italy: eight epithelioid, eight biphasic and eight sarcomatoid. Levels of 7 of the 10 differed significantly by subtype. In epithelioid and biphasic tumors, no link with survival was seen. In the eight sarcomatoid cases, lower levels of miR-17-5p and miR-30c were associated with longer survival (log-rank P of 0.006). The authors said the small number of specimens did not allow firm conclusions. They concluded that microRNAs are potential diagnostic and prognostic markers of mesothelioma.

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: microRNA and gene expression profiling of cultured cell lines, plus measurement of selected microRNAs in archived tumor tissue specimens with survival analysis
• Who was studied: Two human mesothelioma cell lines (MPP-89 and REN) and immortalized non-tumor human mesothelial cells (HMC-TERT). Also 24 primary mesothelioma tissue specimens (8 epithelioid, 8 biphasic, 8 sarcomatoid) from Dell'Angelo Hospital, Zelarino–Venice, Italy, collected at diagnosis from patients who had not received previous treatment. Dates are not given.
• Exposure: No asbestos exposure was measured or studied. The study examined microRNA expression in mesothelioma cells and tissues compared with non-tumor mesothelial cells.
• Main results:
  • In the cell lines, 65 microRNAs were dysregulated across three biological replicates. Both mesothelioma cell lines shared the same 10 up-regulated and 19 down-regulated microRNAs compared with HMC-TERT cells.
  • Checking 10 microRNAs with a second method (qRT-PCR) gave results consistent with the microarray, except for one discrepancy for hsa-miR-21.
  • Combining microRNA data, gene expression data and target prediction identified 587 genes as putative targets of the dysregulated microRNAs.
  • In the 24 tissue specimens, expression of 7 of the 10 microRNAs analyzed was significantly associated with histological subtype (epithelioid, biphasic, sarcomatoid).
  • No association with histological subtype was found for hsa-miR-31, hsa-miR-221 or hsa-miR-222.
  • In the epithelioid and biphasic specimens, no correlation was observed between survival and microRNA expression.
  • In the 8 sarcomatoid specimens, all patients with miR-17-5p or miR-30c expression below the median survived longer than those above the median. The log-rank P value was 0.006.
  • The log-rank P value for the sarcomatoid survival analysis was 0.006 (printed in the scanned text as 'P 5 0.006').
  • No correlations of microRNA expression with tumor stage were observed.
  • All sarcomatoid patients fell into the high-risk group of the EORTC prognostic score.
• The authors' conclusion: The authors concluded that their preliminary analysis points to microRNAs as potential diagnostic and prognostic markers of mesothelioma, and that a larger study is needed to establish the prognostic meaning of miR-17-5p and miR-30c.
• Limitations the authors state:
  • The number of tissue specimens tested was low (eight per subtype).
  • The small study size did not allow the authors to draw firm conclusions.
  • The work does not provide insight into mechanisms of cancer development; further validation studies are required.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Prognosis, Median Overall Survival, Mesothelial Cells, Carcinogenesis, Epithelioid, Biphasic Mesothelioma, Sarcomatoid.

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