Discovery of Previously Undetected MicroRNAs in Mesothelioma and Their Use as Tissue-of-Origin Markers

Our plain-English summary of Discovery of Previously Undetected MicroRNAs in Mesothelioma and Their Use as Tissue-of-Origin Markers, by V.D. Martinez, E.A. Marshall, C. Anderson, et al (American Journal of Respiratory Cell and Molecular Biology, 2019).

The study

• Authors: V.D. Martinez, E.A. Marshall, C. Anderson, K.W. Ng, B.C. Minatel, A.P. Sage, K.S.S. Enfield, Z. Xu, W.L. Lam
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 2019;61(2):266-268
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

In this research letter, the authors tested whether malignant pleural mesothelioma (MPM) tumors express previously undetected microRNA (miRNA) sequences that could distinguish MPM from cancers that spread to the pleura, particularly lung and breast cancers. They analyzed small RNA sequencing data from 87 MPM samples from The Cancer Genome Atlas (TCGA). They compared these with 497 lung adenocarcinomas (LUAD) and 467 lung squamous cell carcinomas from TCGA, 129 lung tumors from the British Columbia Cancer Agency (BCCA), and 1,047 TCGA breast tumors. Using the miRDeep2 algorithm, they identified 2,021 miRNA sequences, of which 1,597 were already annotated in miRBase. After filtering, 154 novel, previously undetected miRNAs remained. Principal component analysis showed that expression of these 154 miRNAs distinguished MPM from the lung tumor cohorts, with similar results for breast tumors. Using a weighted voting class prediction method, the authors built a 10-miRNA classifier trained against TCGA LUAD cases and tested it against 94 BCCA LUAD cases. It correctly identified 86 of 87 MPM cases (98.9%), including two sarcomatoid cases, and all LUAD cases. The one misclassified sample was a biphasic MPM. The authors concluded that the classifier showed high accuracy in distinguishing MPM from LUAD and warrants further investigation.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This research letter reported a laboratory analysis of tumor genetic material. It was not a study of asbestos exposure: asbestos appears only in the opening background sentence. The authors searched small RNA sequencing data from 87 malignant pleural mesothelioma (MPM) samples in The Cancer Genome Atlas for microRNAs, small molecules that regulate genes, that had not been recorded before. They reported 154 novel microRNA sequences in MPM tissue. Expression of these 154 separated MPM from 1,093 lung tumors from two sources, and the authors reported similar results for 1,047 breast tumors. The authors then built a classifier from 10 of the novel microRNAs. They trained it by comparing the MPM cases with 497 lung adenocarcinomas, then tested it against a separate group of 94 lung adenocarcinomas. It correctly identified 86 of 87 MPM cases (98.9%), including two sarcomatoid cases, and all of the lung adenocarcinomas. The one missed case was a biphasic MPM. The authors concluded that the classifier was highly accurate in distinguishing MPM from lung adenocarcinoma and called for further investigation.

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: Research letter reporting a molecular (genetic sequencing) analysis of tumor samples from existing data collections, with development and testing of a classifier
• Who was studied: Tumor samples, not people followed over time. 87 malignant pleural mesothelioma samples, 497 lung adenocarcinomas and 467 lung squamous cell carcinomas, all from The Cancer Genome Atlas. A further 129 lung tumors (94 adenocarcinoma, 35 squamous cell carcinoma) came from the British Columbia Cancer Agency, and 1,047 breast tumors came from The Cancer Genome Atlas. Dates are not given.
• Exposure: No asbestos exposure was studied. Asbestos is mentioned only as background: the opening sentence states that MPM results from occupational exposure to asbestos.
• Main results:
  • The authors identified 2,021 microRNA sequences in the MPM data, 1,597 of which were already annotated. After filtering, they reported 154 novel, previously undetected microRNA sequences in MPM tissues.
  • Expression of the 154 novel microRNAs distinguished MPM from the lung adenocarcinoma and lung squamous cell carcinoma groups from both sources (1,093 lung tumors in total).
  • The authors reported similar results when the 154 microRNAs were compared against breast cancer tumors.
  • One microRNA candidate predicted in both MPM and breast tumors was confirmed in five breast cancer cell lines.
  • The 10-microRNA classifier was tested against the 94 lung adenocarcinomas from the British Columbia Cancer Agency. It correctly identified 86 of the 87 MPM cases (98.9%) and 100% of the lung adenocarcinoma cases.
  • The correctly identified MPM cases included the two samples diagnosed as the sarcomatoid subtype. The authors note that standard staining markers (IHC) are not sufficient for this subtype.
  • The one misclassified MPM sample was a biphasic MPM diagnosed by morphology. The authors note that this tumor also lacked specific staining for mesothelial IHC markers.
• The authors' conclusion: The authors concluded that their classifier of 10 previously undetected microRNAs showed high accuracy in distinguishing MPM from lung adenocarcinoma. They said further investigation is needed into whether these sequences can help classify tumors when morphologic and IHC evaluations are ambiguous.

Topics

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

Medical terms in this study, explained in our Lexicon: Discovery, Mesothelioma, Pleural Mesothelioma, Pleura, Lung Adenocarcinoma, Squamous Cell Carcinoma, Sarcomatoid, Biphasic Mesothelioma.

Related studies

• MiR-score: a novel 6-microRNA signature that predicts survival outcomes in patients with malignant pleural mesothelioma — M.B. Kirschner, Y.Y. Cheng, et al. (2015)
• miR-1254 and miR-574-5p: serum-based microRNA biomarkers for early-stage non-small cell lung cancer — K.M. Foss, C. Sima, et al. (2011)
• Downregulated microRNAs in the differential diagnosis of malignant pleural mesothelioma — G.V. Gee, D.C. Koestler, et al. (2010)
• Role of microRNAs in malignant mesothelioma — A. Truini, S. Coco, et al. (2014)
• MicroRNAs diagnostic and prognostic value as predictive markers for malignant mesothelioma — E. Sturchio, M.G. Berardinelli, et al. (2020)
• MicroRNA signature of malignant mesothelioma with potential diagnostic and prognostic implications — S. Busacca, S. Germano, et al. (2010)

Browse more research in American Journal of Respiratory Cell and Molecular Biology, or return to medical research.