Integrative analysis of microRNA, mRNA and aCGH data reveals asbestos- and histology-related changes in lung cancer

Our plain-English summary of Integrative analysis of microRNA, mRNA and aCGH data reveals asbestos- and histology-related changes in lung cancer, by P. Nymark, M. Guled, I. Borze, et al (Genes, Chromosomes & Cancer, 2011).

The study

• Authors: P. Nymark, M. Guled, I. Borze, A. Faisal, L. Lahti, K. Salmenkivi, E. Kettunen, S. Anttila, S. Knuutila
• Journal: Genes, Chromosomes & Cancer
• Published: 2011;50(8):585-97
• Cited by: 108 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Lung cancer has the highest mortality rate of all of the cancers in the world and asbestos-related lung cancer is one of the leading occupational cancers. The identification of asbestos-related molecular changes has long been a topic of increasing research interest. The aim of this study was to identify novel asbestos-related molecular correlates by integrating miRNA expression profiling with previously obtained profiling data (aCGH and mRNA expression) from the same patient material. miRNA profiling was performed on 26 tumor and corresponding normal lung tissue samples from highly asbestos-exposed and non-exposed patients, and on eight control lung tissue samples. Data analyses on miRNA expression, and integration of miRNA and previously obtained mRNA data were performed using Chipster. A separate analysis was used to integrate miRNA and previously obtained aCGH data. Both known and new lung cancer-associated miRNAs and target genes with inverse correlation were discovered. Furthermore, DNA copy number alterations (e.g., gain at 12p13.31) were correlated with the deregulated miRNAs. Specifically, thirteen novel asbestos-related miRNAs (over-expressed: miR-148b, miR-374a, miR-24-1*, Let-7d, Let-7e, miR-199b-5p, miR-331-3p, and miR-96 and under-expressed: miR-939, miR-671-5p, miR-605, miR-1224-5p and miR-202) and inversely correlated target genes (e.g., GADD45A, LTBP1, FOSB, NCALD, CACNA2D2, MTSS1, EPB41L3) were identified. In addition, over-expression of the well known squamous cell carcinoma-associated miR-205 was linked to down-regulation of the DOK4 gene. The miRNAs/genes presented here may represent interesting targets for further investigation and could eventually have potential diagnostic implications.

Copyright © 2011 Wiley-Liss, Inc.

In plain English

This laboratory study from Helsinki, Finland, measured microRNAs in lung cancer tissue removed during surgery in the 1990s. MicroRNAs are small molecules that help control which genes are active. The authors compared tumor and nearby normal lung from 13 male patients with high asbestos exposure with tissue from 13 non-exposed patients. High exposure meant a work history of exposure plus more than 5 million fibers per gram of dry lung tissue, mainly amphiboles. The two groups were matched for age, smoking and tumor type, and eight control samples were also tested. The results were combined with earlier gene-activity and DNA data from the same patients. The tumors fell into two groups. In one group, mostly adenocarcinomas, eight microRNAs told exposed from non-exposed patients' tumors and classified all samples correctly. A separate analysis of 10 adenocarcinomas found eight, three of them the same. miR-205 was linked to squamous cell carcinoma. It was higher in normal lung from exposed patients with that cancer type. The authors concluded this suggests a role for these microRNAs, but independent experiments are needed to confirm the findings.

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 molecular study (microRNA microarray profiling of surgical lung tissue), comparing asbestos-exposed and non-exposed lung cancer patients and integrating the results with previously obtained mRNA and aCGH (DNA copy number) data from the same samples
• Who was studied: Tumor and corresponding normal lung samples from 13 highly asbestos-exposed and 13 non-exposed lung cancer patients, all male and Finnish, matched for age, smoking history and tumor histology. Samples were obtained during surgery at Helsinki University Central Hospital in the 1990s. Eight control samples were also analyzed: seven lung tissue samples from patients without cancer and one commercial lung RNA sample.
• Exposure: Exposed patients had definite or probable exposure according to work history and a lung asbestos fiber count above 5 million fibers per gram of dry lung tissue (mainly amphiboles), measured by electron microscopy. Non-exposed patients had no known exposure and a fiber count of 0, or in one case 0.5, million fibers per gram.
• Main results:
  • Thirty-four microRNAs differed between tumor and normal samples (FDR less than 0.05). They divided the tumors into two groups. Adenocarcinomas were more frequent in Group 1 (8/13, 62%) than in Group 2 (2/13, 15%).
  • In cancer Group 1, eight microRNAs (FDR less than 0.05) distinguished asbestos-exposed from non-exposed patients' samples and classified all samples correctly. Over-expressed in asbestos-related samples were miR-148b, miR-374a and miR-24-1*. Under-expressed were miR-939, miR-671-5p, miR-605, miR-1224-5p and miR-202.
  • In cancer Group 1, over-expression of miR-148b correlated with down-regulation of the genes GADD45A, LTBP1 and FOSB.
  • Among adenocarcinoma samples (five exposed and five non-exposed), eight microRNAs (FDR less than 0.07) classified all samples correctly. Three of them were the same as in cancer Group 1.
  • Three of four asbestos-related adenocarcinoma samples showed a DNA loss at 10q26, compared with none of four non-related adenocarcinoma samples. This region contains miR-202, which was under-expressed in asbestos-related samples.
  • Comparing adenocarcinoma with squamous cell carcinoma identified miR-205 as specific to squamous cell carcinoma. Its over-expression correlated with down-regulation of the gene DOK4.
  • In patients with squamous cell carcinoma, miR-205 was over-expressed in the normal lung samples of exposed patients compared with non-exposed patients (FDR less than 0.15).
  • In tumors, over-expression of miR-141 and miR-200c correlated with DNA copy number gains at their location (12p13.31).
  • One hundred microRNAs differed between normal lung from cancer patients and control samples (FDR less than 0.05).
• The authors' conclusion: The authors concluded that they had identified novel asbestos- and histology-associated microRNAs and that their most significant observations strongly suggest a role for these microRNAs in asbestos-related lung cancer or in lung cancer with squamous cell histology. They added that independent experiments are needed to confirm the findings.
• Limitations the authors state:
  • The authors state that independent experiments are needed to confirm the findings.

Topics

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

Medical terms in this study, explained in our Lexicon: Histology, Lung Cancer, Squamous Cell Carcinoma.

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