Cell protection, resistance and invasiveness of two malignant mesotheliomas as assessed by 10K-microarray

Our plain-English summary of Cell protection, resistance and invasiveness of two malignant mesotheliomas as assessed by 10K-microarray, by S. Mohr, G. Keith, F. Galateau-Salle, et al (Biochimica et Biophysica Acta, 2004).

The study

• Authors: S. Mohr, G. Keith, F. Galateau-Salle, P. Icard, B.H. Rihn
• Journal: Biochimica et Biophysica Acta
• Published: 2004;1688(1):43-60
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive serosal tumor, strongly associated with former exposure to asbestos fibers and for which there is currently no effective treatment available. In human, MPM is characterized by a high local invasiveness, poor prognosis and therapeutic outcomes. In order to assess molecular changes that specify this phenotype, we performed a global gene expression profiling of human MPM. Using a 10,000-element microarray, we analyzed mRNA relative gene expression levels by comparing a mesothelioma cell line to either a pleural cell line or tumor specimens. To analyze these gene expression data, we used various bioinformatics softwares. Hierarchical clustering methods were used to group genes and samples with similar expression in an unsupervised mode. Genes of known function were further sorted by enzyme, function and pathway clusters using a supervised software (IncyteGenomics). Taken together, these data defined a molecular fingerprint of human MPM with more than 700 up- or down-regulated genes related to several traits of the malignant phenotype, specially associated with MPM invasiveness, protection and resistance to anticancer defenses. This portrait is meaningful in disease classification and management, and relevant in finding new specific markers of MPM. These molecular markers should improve the accuracy of mesothelioma diagnosis, prognosis and therapy.

In plain English

This laboratory study measured gene activity in malignant pleural mesothelioma. The authors used a microarray of about 10,000 elements to analyze two tumor specimens, labeled "Sp" and "Fa", obtained at surgery. Both tumors were of the epithelial subtype. Because they lacked enough non-malignant pleura, the authors compared each tumor to a mesothelioma cell line (MSTO-211H) in four repeat experiments. They then compared the results indirectly with a pleural cell line (MET-5A) profiled in their earlier study. The article does not report the patients' asbestos exposure. Of 9984 elements screened, 5402 genes passed quality filters, and 757 genes differed in activity between the mesothelioma samples and the pleural cells. In clustering analysis the two tumors grouped apart from the pleural cells. Genes more active in the tumors included genes linked to DNA repair, adhesion and protease inhibition. Several cell-junction genes were less active. The authors concluded that the tumors enhanced gene clusters that promote invasion, cell protection and resistance. They noted that whole-tissue samples may dilute some signals and that the results still need validation in more tumors.

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 (cDNA microarray) study of human tumor tissue and cell lines
• Who was studied: Two malignant pleural mesothelioma tumor specimens ("Sp" and "Fa"), both epithelial subtype, obtained at surgery at CHU Côte de Nacre, Caen, France. Also the mesothelioma cell line MSTO-211H and, from the authors' previous study, the pleural cell line MET-5A.
• Exposure: No asbestos exposure was measured or reported for the patients. The study compared gene activity (mRNA) of the two tumors against a mesothelioma cell line used as a common reference, and indirectly against a pleural cell line.
• Main results:
  • After filtering, 5402 of the 9984 screened genes were retained for analysis
  • 757 genes were differentially expressed in the mesothelioma samples (cells and/or tissues) compared with the pleural cells
  • Of these, 62 over-expressed and 48 down-regulated genes had also been found in the authors' earlier cell line study and were confirmed in the tumor tissues
  • In hierarchical clustering, the two mesothelioma tumors grouped separately from the pleural cells
  • In the 'ecological interaction' gene group, the ratio of over-expressed to under-expressed genes was 5.2 for all differentially expressed genes. It was 8.5 when only genes changed in both tumors were counted.
  • The DNA repair-related gene GADD45A was over-expressed in both tumors; the authors suggested this may protect cancer cells
  • Several genes for cell junction components were down-regulated in the mesothelioma samples
  • The cadherin gene CDH11 was over-expressed in both tumors
  • The protease-inhibitor gene A2M was over-expressed in both tumors
• The authors' conclusion: The authors concluded that the mesothelioma tumors showed enhanced expression of gene clusters that promote invasion, cell protection and resistance. They suggested these genes may help explain the tumor's resistance to therapy.
• Limitations the authors state:
  • There was not enough non-malignant pleura for a direct tissue-to-tissue comparison, so the comparison with normal pleural cells was indirect, through cell lines
  • Because whole tissues were studied, some apparent down-regulation may reflect dilution rather than the tumor itself
  • The findings, based on two tumors, still need validation and functional analysis in a larger set of mesotheliomas
  • Only epithelial mesotheliomas were studied; comparison with other mesothelioma types and lung tumors is still needed

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Pleural Mesothelioma, Prognosis, Mesothelioma.

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