The expression of Dishevelled-3 and glutamine metabolism in malignant pleural mesothelioma

Our plain-English summary of The expression of Dishevelled-3 and glutamine metabolism in malignant pleural mesothelioma, by T. Li, S.C. Hou, J.H. Mao, et al (Journal of Clinical Pathology, 2012).

The study

• Authors: T. Li, S.C. Hou, J.H. Mao, Y.C. Wang, X.D. Lu, J.L. Tan, B. You, Y.P. Liu, J. Ni, A. Au, D.M. Jablons, Z. Xu, L. You
• Journal: Journal of Clinical Pathology
• Published: 2012;65(9):855-8
• Type of article: Letter
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Summary of the article

This short report examined whether expression of Dishevelled-3 (Dvl3), a Wnt pathway protein, and two glutamate-handling proteins, excitatory amino acid transporter 1 (EAAT1) and glutamine synthetase (GS), were associated with each other and with survival in malignant pleural mesothelioma (MPM). The authors used clinical data from 39 patients with primary MPM between 1997 and 2009 and 38 mesothelioma tissue samples. Seven of these samples included adjacent normal pleura, and normal pleura from three further patients was on tissue microarray sections. They also studied six mesothelioma cell lines and one normal mesothelial cell line (LP9). Methods were immunohistochemistry, real-time PCR, western blot, Kaplan–Meier and log-rank analysis, and Cox regression. EAAT1 staining was positive in 97.4% (37/38) of mesothelioma samples and 50% (5/10) of normal pleura samples. GS was positive in 91.7% (33/36) and 80% (8/10), and Dvl3 in 97.0% (32/33) and 43% (3/7). EAAT1 staining was associated with survival (p=0.028), as was Dvl3 staining (p=0.001; Cox regression p=0.007). GS staining correlated with EAAT1 (p=0.002) and Dvl3 (p=0.036) staining but not with survival (p=0.353). Disease stage correlated with survival (p<0.01). EAAT1 and GS staining was positive in five mesothelioma cell lines and negative in H28 and LP9. The authors concluded that stronger EAAT1 staining went with shorter survival and that EAAT1, GS and Dvl3 need further study as possible therapeutic targets.

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In plain English

This short laboratory report studied three proteins in malignant pleural mesothelioma: Dishevelled-3 (Dvl3), the glutamate transporter EAAT1, and the enzyme glutamine synthetase (GS). The authors used clinical data from 39 patients with primary malignant pleural mesothelioma (1997 to 2009). Of 38 tumour samples obtained, between 33 and 38 per protein were stained, along with normal pleura samples; six mesothelioma cell lines and one normal mesothelial cell line were also tested. EAAT1 staining was positive in 37 of 38 mesothelioma samples and 5 of 10 normal pleura samples. GS staining was positive in 33 of 36 and 8 of 10. Dvl3 staining was positive in 32 of 33 and 3 of 7. The degree of EAAT1 staining (p=0.028) and of Dvl3 staining (p=0.001) was associated with survival time. GS staining was not significantly associated with survival (p=0.353). Disease stage was also associated with survival. The article does not discuss asbestos exposure. The authors concluded that mesothelioma cells express more EAAT1 than normal cells, that further studies of the three proteins are needed, and that the proteins may serve as potential therapy targets.

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 study (short report) of protein staining in tumour and normal tissue samples and cell lines, with survival analysis
• Who was studied: 39 patients with primary malignant pleural mesothelioma (1997 to 2009), with 38 mesothelioma tissue samples. Seven of these included adjacent normal pleura, and normal pleura came from another three patients. The study also used mesothelioma cell lines H28, 211H, H2052, MS-1, H290 and H513 and the normal mesothelial cell line LP9. Samples were analysed under a University of California, San Francisco review board approval.
• Exposure: Not reported. The article does not describe asbestos or any other exposure of the patients. It measured expression of Dvl3, EAAT1 and GS.
• Main results:
  • Among the patients, disease stage correlated significantly with survival time (p<0.01); surgical procedure did not.
  • EAAT1 staining was positive in 97.4% (37/38) of mesothelioma samples and 50% (5/10) of normal pleura samples.
  • GS staining was positive in 91.7% (33/36) of mesothelioma samples and 80% (8/10) of normal pleura samples.
  • Dvl3 staining was positive in 97.0% (32/33) of mesothelioma samples and 43% (3/7) of normal pleura samples.
  • In the patient samples, the degree of EAAT1 staining was significantly associated with survival time (p=0.028). The authors described this as stronger staining going with shorter survival.
  • GS staining correlated with EAAT1 staining (p=0.002) and Dvl3 staining (p=0.036). Its association with survival time was not statistically significant (p=0.353).
  • Dvl3 staining correlated with EAAT1 staining (p=0.035) and was associated with survival time (p=0.001). In Cox regression analysis, Dvl3 staining was significantly correlated with survival time (p=0.007).
  • In the cell lines, EAAT1 and GS staining was positive in five mesothelioma lines (H2052, H513, MS-1, 211H, H290). It was negative in the mesothelioma line H28 and the normal line LP9.
  • By western blot, EAAT1 protein was high in H2052, MS-1, 211H, H513 and H290, and low in H28 and LP9.
• The authors' conclusion: The authors concluded that mesothelioma cells express more EAAT1 than normal cells and that further studies of EAAT1, Dvl3 and GS in mesothelioma are needed. They suggested the three proteins may serve as potential therapeutic targets in the future.
• Limitations the authors state:
  • Pathological type, stage, surgical procedure and survival information was not available for every sample.
  • Some patient samples were not available for staining: one for EAAT1, three for GS and six for Dvl3.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Mesothelioma, Pleura, Mesothelial Cells, Immunohistochemistry.

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