Identification of intelectin overexpression in malignant pleural mesothelioma by serial analysis of gene expression (SAGE)

Our plain-English summary of Identification of intelectin overexpression in malignant pleural mesothelioma by serial analysis of gene expression (SAGE), by A. Wali, P.J. Morin, C.D. Hough, et al (Lung Cancer, 2005).

The study

• Authors: A. Wali, P.J. Morin, C.D. Hough, F. Lonardo, T. Seya, M. Carbone, H.I. Pass
• Journal: Lung Cancer
• Published: 2005;48(1):19-29
• Cited by: 32 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is a fatal neoplasm with no acceptable curative approaches. We used serial analysis of gene expression (SAGE) to compare the gene expression pattern of a surgically resected MPM to the autologous normal mesothelium. Intelectin gene overexpression (>139-fold) was found in the tumor. Online SAGE datasets revealed intelectin to be consistently present in mesothelioma(s), ovarian cancer, and colon cancer. Intelectin mRNA expression was found by RT-PCR in 4 of 5 resected MPM tumors, and Intelectin protein expression was confirmed by immunohistochemistry in 28 of 53 MPM tumors, and in 4 of 4 mesothelioma cell lines studied by Western blot. A marked induction in intelectin gene expression was observed among human primary mesothelial cells as a consequence of crocidolite asbestos exposure and simian virus 40 infection. Intelectin overexpression in mesothelioma could have potential screening, and therapeutic implications.

In plain English

This laboratory study looked for genes more active in malignant pleural mesothelioma than normal tissue. Using serial analysis of gene expression (SAGE), the authors compared a tumor from a 39-year-old man with his own uninvolved peritoneum. A gene called intelectin was among the most overexpressed: 139-fold in the article's table, greater than 129-fold in its text. Intelectin appeared in 14 of 94 libraries in an online gene database. RT-PCR testing found intelectin in three of five mesothelioma tumors according to the text; the abstract says 4 of 5. In tissue staining, 28 of 53 resected mesotheliomas were positive, as were 2 of 14 lung adenocarcinomas. Most of 24 further tumors had higher intelectin levels than normal peritoneum. In lab-grown mesothelial cells from two heart failure patients, intelectin rose two-fold after 2 hours of crocidolite asbestos or 48 hours of infection with wild-type SV40 virus (strain 776). A mutant SV40 strain alone caused only a marginal increase. The authors concluded intelectin could have potential screening and therapeutic uses. They said how far the lab results reflect events in the body remains unclear.

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- and protein-expression study: SAGE comparison of one tumor with matching normal tissue, followed by RT-PCR, Western blot, immunohistochemistry, gene microarrays, and an in vitro cell-culture experiment
• Who was studied: A mesothelioma tumor and uninvolved peritoneum from one 39-year-old male patient (R096). Confirmatory work used other archived tumors, 5 tumors by RT-PCR, a tissue microarray of 53 resected malignant pleural mesotheliomas, 24 further tumors by gene microarray, four mesothelioma cell lines, and primary mesothelial cultures from two congestive heart failure patients. The tissue came from Detroit (Karmanos Thoracic Oncology Archives and Harper University Hospital). Dates were not given.
• Exposure: Patients' asbestos exposure was not reported. In the cell experiment, primary human mesothelial cultures were treated with crocidolite asbestos for 2 hours, infected with SV40 (wild-type strain 776 or the mutant dl883) for 48 hours, or given both.
• Main results:
  • In the SAGE comparison of tumor R096 with its matching peritoneum, the intelectin tag was among the 20 most overexpressed tags. The text gives greater than 129-fold; Table 1 lists 139.
  • In the online SAGE database, 14 of 94 libraries contained the intelectin tag.
  • By RT-PCR, intelectin expression was present in three out of five MPM tumors, according to the text.
  • By immunohistochemistry, 28 of 53 resected malignant pleural mesotheliomas were positive for intelectin.
  • In lung cancer, intelectin staining was positive in 2 of 14 adenocarcinomas. It was negative in 10 squamous cell carcinomas and 6 small cell carcinomas.
  • In 24 MPM tumors analyzed by microarray, most cases had higher intelectin gene expression than normal peritoneum.
  • By Western blot, all four mesothelioma cell lines showed higher intelectin protein levels than SV40-immortalized mesothelial foci 1 and 4.
  • In two sets of primary human mesothelial cultures, intelectin gene expression rose two-fold after crocidolite asbestos for 2 hours or wild-type SV40 strain 776 for 48 hours. The SV40 mutant dl883 alone caused a marginal increase. Adding crocidolite during the last 2 hours of dl883 infection increased expression further.
• The authors' conclusion: The authors concluded that intelectin overexpression in mesothelioma could have potential screening and therapeutic implications.
• Limitations the authors state:
  • The authors stated that it remains unclear to what extent the in vitro asbestos and SV40 experiments reflect what happens in the body.
  • The authors stated that further studies are needed to evaluate intelectin as a marker for telling mesothelioma apart from other cancers.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Neoplasm, Mesothelium, Mesothelioma, Ovarian Cancer, Colorectal Cancer, Immunohistochemistry, Mesothelial Cells.

Related studies

• Identification of DAB2 and Intelectin-1 as Novel Positive Immunohistochemical Markers of Epithelioid Mesothelioma by Transcriptome Microarray Analysis for Its Differentiation From Pulmonary Adenocarcinoma — M. Kuraoka, V.J. Amatya, et al. (2017)
• Clinicopathological significance of intelectin-1 in colorectal cancer: Intelectin-1 participates in tumor suppression and favorable progress — N. Katsuya, K. Sentani, et al. (2020)
• Specific expression of human intelectin-1 in malignant pleural mesothelioma and gastrointestinal goblet cells — K. Washimi, T. Yokose, et al. (2012)
• Gene expression profiles reveal increased mClca3 (Gob5) expression and mucin production in a murine model of asbestos-induced fibrogenesis — T. Sabo-Attwood, M. Ramos-Nino, et al. (2005)
• Identification of novel candidate oncogenes and tumor suppressors in malignant pleural mesothelioma using large-scale transcriptional profiling — G.J. Gordon, G.N. Rockwell, et al. (2005)
• SV40-induced expression of calretinin protects mesothelial cells from asbestos cytotoxicity and may be a key factor contributing to mesothelioma pathogenesis — T. Henzi, W.V. Blum, et al. (2009)

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