Snail expression is associated with a poor prognosis in malignant pleural mesotheliomas

Our plain-English summary of Snail expression is associated with a poor prognosis in malignant pleural mesotheliomas, by M. Kobayashi, C.L. Huang, M. Sonobe, et al (The Annals of Thoracic Surgery, 2013).

The study

• Authors: M. Kobayashi, C.L. Huang, M. Sonobe, R. Kikuchi, M. Ishikawa, N. Imamura, J. Kitamura, S. Iwakiri, K. Itoi, R. Yasumizu, H. Date
• Journal: The Annals of Thoracic Surgery
• Published: 2013;95(4):1181-8
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Malignant pleural mesotheliomas (MPMs) are aggressive tumors with a poor prognosis. We aimed to clarify the mechanisms of epithelial-to-mesenchymal transition (EMT) in MPMs by analyzing the expressions of EMT-associated transcription factors and E-cadherin in relation to tumor proliferation rates and patient survival.

Methods: One hundred nine patients with MPMs were investigated. Among these patients, there were 61 epithelioid tumors, 21 sarcomatoid tumors, 20 biphasic tumors, and 7 desmoplastic tumors. Immunohistochemical analyses were performed to evaluate the expressions of Snail, ZEB1, Twist, E-cadherin, and the Ki-67 proliferation index.

Results: The expressions of Snail and ZEB1 were significantly higher in the nonepithelioid tumors than in the epithelioid tumors (p<0.0001 and p=0.0051, respectively). Furthermore, the E-cadherin expression was significantly lower in the Snail-high tumors than in the Snail-low tumors (p=0.0423). The E-cadherin expression was significantly lower in the nonepithelioid tumors than in the epithelioid tumors (p=0.0126). The Ki-67 proliferation index was significantly higher in the nonepithelioid tumors than in the epithelioid tumors (p=0.025). Patient survival was significantly lower in patients with Snail-high MPMs than in those with Snail-low MPMs (p=0.0016), especially in patients with nonepithelioid tumors (p=0.0089). The multivariate analysis also demonstrated that nuclear Snail expression was a significant predictor of poor prognosis in patients with MPMs (p=0.0142).

Conclusions: The Snail expression is associated with EMT and a poor prognosis in MPMs. Snail could be a potential molecular target for the treatment of patients with MPMs.

Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

In plain English

This study, from three hospitals in Japan, examined tumor tissue from 109 consecutive patients diagnosed with malignant pleural mesothelioma between 1998 and 2010. There were 61 epithelioid tumors and 48 nonepithelioid (sarcomatoid, biphasic or desmoplastic) tumors. Staining measured proteins linked to epithelial-to-mesenchymal transition, a shift toward more aggressive tumor cells: Snail, ZEB1, Twist and E-cadherin, plus the growth marker Ki-67. Asbestos exposure was recorded as yes for 52 patients, no for 33 and unknown for 24; fiber types were not described. Nonepithelioid tumors had more Snail and ZEB1 and less E-cadherin than epithelioid tumors. Two-year survival was 18.7% with Snail-high tumors versus 41.1% with Snail-low tumors (p=0.0016). In multivariate analysis, high Snail had a hazard ratio of 2.396 (95% confidence interval 1.190 to 3.047). Snail was significantly associated with reported asbestos exposure, but asbestos exposure was not a significant survival factor. The authors concluded that Snail expression is associated with EMT and a poor prognosis and could be a potential treatment target. They said some results might partly reflect the small number of patients.

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: Clinicopathologic study: immunohistochemical staining of tumor tissue from consecutive patients, analyzed against tumor type and patient survival (Kaplan-Meier, log-rank and Cox multivariate analysis)
• Who was studied: 109 consecutive patients with malignant pleural mesothelioma diagnosed at Kyoto University Hospital, Hyogo Prefectural Amagasaki Hospital, or Hyogo Prefectural Tsukaguchi Hospital in Japan, January 1998 to December 2010. They had 61 epithelioid, 21 sarcomatoid, 20 biphasic and 7 desmoplastic tumors. 81 were male and 28 female; median age was 65 (range 47 to 82).
• Exposure: The study's main factors were tumor protein markers (Snail, ZEB1, Twist, E-cadherin, Ki-67), not asbestos. Asbestos exposure was recorded as a patient characteristic: yes in 52 patients (47.8%), no in 33 (30.2%), unknown in 24 (22%). No fiber types, sources or doses were given.
• Main results:
  • The Ki-67 proliferation index was significantly higher in nonepithelioid tumors than in epithelioid tumors (54.1% versus 40.2%).
  • The 2-year survival rate was significantly lower in patients with nonepithelioid tumors than in those with epithelioid tumors (18.8% versus 48.0%).
  • The percentage of tumor cells with nuclear Snail staining was significantly higher in nonepithelioid tumors than in epithelioid tumors (48.9% versus 26.1%; the abstract gives p<0.0001).
  • E-cadherin-positive tumor cells were 8.6% in nonepithelioid tumors and 21.3% in epithelioid tumors, a significant difference (p=0.0126).
  • Nuclear ZEB1 staining was significantly higher in nonepithelioid tumors than in epithelioid tumors (16.1% versus 6.4%; p=0.0051). Twist staining did not differ by tumor type.
  • E-cadherin-positive tumor cells were significantly fewer in Snail-high tumors (9.0%) than in Snail-low tumors (19.7%) (p=0.0423). No significant E-cadherin difference was found by ZEB1 or Twist status.
  • The Ki-67 index was higher in Snail-high than in Snail-low tumors (51.9% versus 42.8%), but the difference was not statistically significant.
  • Among all 109 patients, the 2-year survival rate was significantly lower with Snail-high tumors than with Snail-low tumors (18.7% versus 41.1%; p=0.0016).
  • Among the 48 patients with nonepithelioid tumors, 2-year survival was 4.1% with Snail-high tumors versus 38.9% with Snail-low tumors (p=0.0089).
  • Survival was lower with ZEB1-high tumors than with ZEB1-low tumors, but not significantly so (p 0.0733). There was no significant survival difference by Twist status.
  • In the multivariate Cox analysis, three factors were significant prognostic factors:
• Snail status: hazard ratio 2.396 (95% CI 1.190 to 3.047; p=0.0142).
• Tumor histologic type: hazard ratio 1.973 (CI 1.200 to 3.245).
• Pathologic stage: hazard ratio 1.423 (CI 1.004 to 2.015).
  • Nuclear Snail expression was significantly associated with asbestos exposure: 39.4% of tumor cells in exposed patients versus 26.4% in unexposed patients (Table 2, p 0.0322). E-cadherin, ZEB1 and Twist showed no difference by asbestos exposure.
  • In the multivariate survival analysis, asbestos exposure (yes versus no) was not a significant factor: hazard ratio 0.745 (95% CI 0.441 to 1.259; p 0.2710).
• The authors' conclusion: The authors concluded that Snail expression is associated with epithelial-to-mesenchymal transition and a poor prognosis in malignant pleural mesotheliomas, and that Snail could be a potential molecular target for treatment.
• Limitations the authors state:
  • The authors said that the lack of significant survival differences by ZEB1 status, Twist status and treatment might partly result from the relatively small number of patients.

Topics

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

Medical terms in this study, explained in our Lexicon: Prognosis, Pleural Mesothelioma, Epithelioid, Sarcomatoid, Biphasic Mesothelioma, Desmoplastic Mesothelioma, Ki-67, Multivariate Analysis.

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• NF2 blocks Snail-mediated p53 suppression in mesothelioma — J.H. Cho, S.J. Lee, et al. (2015)
• High Expression of SMO and GLI1 Genes with Poor Prognosis in Malignant Mesothelioma — G.Y. Ma, S. Shi, et al. (2023)

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