Expression status of candidate genes in mesothelioma tissues and cell lines

Our plain-English summary of Expression status of candidate genes in mesothelioma tissues and cell lines, by O. Melaiu, E. Melissari, L. Mutti, et al (Mutation Research, 2015).

The study

• Authors: O. Melaiu, E. Melissari, L. Mutti, E. Bracci, C. De Santi, C. Iofrida, M. Di Russo, A. Cristaudo, A. Bonotti, M. Cipollini, S.I. Garritano, R. Foddis, M. Lucchi, S. Pellegrini, F. Gemignani, S. Landi
• Journal: Mutation Research
• Published: 2015;771:6-12
• Cited by: 30 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In order to broaden knowledge on the pathogenesis of malignant pleural mesothelioma (MPM), we reviewed studies on the MPM-transcriptome and identified 119 deregulated genes. However, there was poor consistency among the studies. Thus, the expression of these genes was further investigated in the present work using reverse transcriptase-quantitative PCR (RT-qPCR) in 15 MPM and 20 non-MPM tissue samples. Fifty-nine genes showed a statistically significant deregulation and were further evaluated in two epithelioid MPM cell lines (compared to MET-5A, a non-MPM cell line). Nine genes (ACSL1, CCNO, CFB, PDGFRB, SULF1, TACC1, THBS2, TIMP3, XPOT) were deregulated with statistical significance in both cell lines, 12 (ASS1, CCNB1, CDH11, COL1A1, CXADR, EIF4G1, GALNT7, ITGA4, KRT5, PTGIS, RAN, SOD1) in at least one cell line, whereas 7 (DSP, HEG1, MCM4, MSLN, NME2, NMU, TNPO2) were close but did not reach the statistical significance in any of the cell line. Patients whose MPM tissues expressed elevated mRNA levels of BIRC5, DSP, NME2, and THBS2 showed a statistically significant shorter overall survival. Although MPM is a poorly studied cancer, some features are starting to emerge. Novel cancer genes are suggested here, in particular those involved in cell-cell and cell-matrix interactions.

Copyright © 2014 Elsevier B.V. All rights reserved.

In plain English

This laboratory study followed up the authors' earlier review of gene-activity studies in malignant pleural mesothelioma (MPM). That review had flagged 119 genes, but the studies agreed poorly. The authors measured these genes' activity (mRNA levels) in tumour samples from 15 patients with epithelioid MPM and 20 normal pleura samples from patients operated on for early-stage lung cancer. About 73% of MPM patients had an ascertained history of asbestos exposure. The article did not report fiber types. Fifty-nine genes differed significantly between tumour and normal tissue: 51 more active, 8 less. These were then tested in two MPM cell lines against a non-cancerous mesothelial line. Of genes changing in the same direction as in tumour tissue, nine differed significantly in both lines and 12 in one only. No single gene clearly separated MPM from normal tissue. Among 13 patients with survival data, higher levels of BIRC5, NME2, DSP and THBS2 were linked to shorter survival before, but not after, correction for multiple testing. The authors named nine genes as the strongest candidate cancer genes and called for further study.

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 gene-expression study (RT-qPCR) of tumour and control tissues and of cell lines, testing 119 genes identified in the authors' earlier review of transcriptome studies
• Who was studied: 15 epithelioid malignant pleural mesothelioma biopsies and 20 normal pleura samples from patients operated on for early-stage lung cancer (6 lung adenocarcinomas, 14 lung squamous cell carcinomas), University Hospital of Pisa, Italy. Also two epithelioid MPM cell lines (Mero-14, Mero-25) and one non-MPM mesothelial cell line (MeT-5A).
• Exposure: About 73% of MPM patients had an ascertained history of asbestos exposure, and about half of them also had a smoking history. No fiber types, jobs or doses were reported.
• Main results:
  • Of 119 candidate genes, 59 differed in expression between MPM and normal pleural tissue with statistical significance: 51 were up-regulated and 8 down-regulated.
  • Overall, 99 of the 119 candidate genes (83%) changed in the direction expected from earlier transcriptomic studies.
  • In the cell lines, 28 genes changed in the same direction as in the tumour tissues in at least one MPM cell line. The remaining genes did not match the direction seen in tissues.
  • Among the genes changing in the same direction as in tissues, 9 were significantly deregulated in both MPM cell lines.
  • Among the genes changing in the same direction as in tissues, 12 more reached statistical significance in one cell line only.
  • No single differentially expressed gene clearly distinguished MPM from normal pleural tissue.
  • Among MPM patients (survival data for 13), higher expression of BIRC5, NME2, DSP and THBS2 was linked to shorter overall survival only at a nominal level of 0.05. No gene remained associated with survival after correction for multiple tests.
  • The genes that differed in tissue were over-represented in 19 biological pathways, including cell cycle, focal adhesion and cell–matrix interaction.
• The authors' conclusion: The authors concluded that ACSL1, CCNO, CFB, PDGFRB, SULF1, THBS2, TIMP3, XPOT and TACC1 were the strongest candidate cancer genes for MPM. They named a further set of genes as novel potential cancer genes deserving further study.
• Limitations the authors state:
  • Two cell lines might not fully represent MPM, given how varied the cancer is.
  • The survival analysis may have had limited statistical power because few patients were analysed.

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, Pleural Mesothelioma, Epithelioid, Statistical Significance, HEG1, Overall Survival.

Related studies

• Expression of the Wilms' tumor gene WT1 in human malignant mesothelioma cell lines and relationship to platelet-derived growth factor A and insulin-like growth factor 2 expression — A.W. Langerak, K.A. Williamson, et al. (1995)
• A review of transcriptome studies combined with data mining reveals novel potential markers of malignant pleural mesothelioma — O. Melaiu, A. Cristaudo, et al. (2012)
• Specific expression of human intelectin-1 in malignant pleural mesothelioma and gastrointestinal goblet cells — K. Washimi, T. Yokose, et al. (2012)
• A common polymorphism within MSLN affects miR-611 binding site and soluble mesothelin levels in healthy people — S. Garritano, C. De Santi, et al. (2014)
• Gene expression of mesothelioma in vinylidene chloride-exposed F344/N rats reveal immune dysfunction, tissue damage, and inflammation pathways — P.E. Blackshear, A.R. Pandiri, et al. (2015)
• ERC/mesothelin is expressed in human gastric cancer tissues and cell lines — T. Ito, K. Kajino, et al. (2014)

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