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Smad2 and Smad6 as predictors of overall survival in oral squamous cell carcinoma patients
BACKGROUND: To test if the expression of Smad1-8 mRNAs were predictive of survival in patients with oral squamous cell carcinoma (SCC). PATIENTS AND METHODS: We analyzed, prospectively, the expression of Smad1-8, by means of Ribonuclease Protection Assay in 48 primary, operable, oral SCC. In additio...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885344/ https://www.ncbi.nlm.nih.gov/pubmed/20462450 http://dx.doi.org/10.1186/1476-4598-9-106 |
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author | Mangone, Flavia RR Walder, Fernando Maistro, Simone Pasini, Fátima S Lehn, Carlos N Carvalho, Marcos B Brentani, M Mitzi Snitcovsky, Igor Federico, Miriam HH |
author_facet | Mangone, Flavia RR Walder, Fernando Maistro, Simone Pasini, Fátima S Lehn, Carlos N Carvalho, Marcos B Brentani, M Mitzi Snitcovsky, Igor Federico, Miriam HH |
author_sort | Mangone, Flavia RR |
collection | PubMed |
description | BACKGROUND: To test if the expression of Smad1-8 mRNAs were predictive of survival in patients with oral squamous cell carcinoma (SCC). PATIENTS AND METHODS: We analyzed, prospectively, the expression of Smad1-8, by means of Ribonuclease Protection Assay in 48 primary, operable, oral SCC. In addition, 21 larynx, 10 oropharynx and 4 hypopharynx SCC and 65 matched adjacent mucosa, available for study, were also included. For survival analysis, patients were categorized as positive or negative for each Smad, according to median mRNA expression. We also performed real-time quantitative PCR (QRTPCR) to asses the pattern of TGFβ1, TGFβ2, TGFβ3 in oral SCC. RESULTS: Our results showed that Smad2 and Smad6 mRNA expression were both associated with survival in Oral SCC patients. Cox Multivariate analysis revealed that Smad6 positivity and Smad2 negativity were both predictive of good prognosis for oral SCC patients, independent of lymph nodal status (P = 0.003 and P = 0.029, respectively). In addition, simultaneously Smad2(- )and Smad6(+ )oral SCC group of patients did not reach median overall survival (mOS) whereas the mOS of Smad2(+)/Smad6(- )subgroup was 11.6 months (P = 0.004, univariate analysis). Regarding to TGFβ isoforms, we found that Smad2 mRNA and TGFβ1 mRNA were inversely correlated (p = 0.05, R = -0.33), and that seven of the eight TGFβ1(+ )patients were Smad2(-). In larynx SCC, Smad7(- )patients did not reach mOS whereas mOS of Smad7(+ )patients were only 7.0 months (P = 0.04). No other correlations were found among Smad expression, clinico-pathological characteristics and survival in oral, larynx, hypopharynx, oropharynx or the entire head and neck SCC population. CONCLUSION: Smad6 together with Smad2 may be prognostic factors, independent of nodal status in oral SCC after curative resection. The underlying mechanism which involves aberrant TGFβ signaling should be better clarified in the future. |
format | Text |
id | pubmed-2885344 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-28853442010-06-15 Smad2 and Smad6 as predictors of overall survival in oral squamous cell carcinoma patients Mangone, Flavia RR Walder, Fernando Maistro, Simone Pasini, Fátima S Lehn, Carlos N Carvalho, Marcos B Brentani, M Mitzi Snitcovsky, Igor Federico, Miriam HH Mol Cancer Research BACKGROUND: To test if the expression of Smad1-8 mRNAs were predictive of survival in patients with oral squamous cell carcinoma (SCC). PATIENTS AND METHODS: We analyzed, prospectively, the expression of Smad1-8, by means of Ribonuclease Protection Assay in 48 primary, operable, oral SCC. In addition, 21 larynx, 10 oropharynx and 4 hypopharynx SCC and 65 matched adjacent mucosa, available for study, were also included. For survival analysis, patients were categorized as positive or negative for each Smad, according to median mRNA expression. We also performed real-time quantitative PCR (QRTPCR) to asses the pattern of TGFβ1, TGFβ2, TGFβ3 in oral SCC. RESULTS: Our results showed that Smad2 and Smad6 mRNA expression were both associated with survival in Oral SCC patients. Cox Multivariate analysis revealed that Smad6 positivity and Smad2 negativity were both predictive of good prognosis for oral SCC patients, independent of lymph nodal status (P = 0.003 and P = 0.029, respectively). In addition, simultaneously Smad2(- )and Smad6(+ )oral SCC group of patients did not reach median overall survival (mOS) whereas the mOS of Smad2(+)/Smad6(- )subgroup was 11.6 months (P = 0.004, univariate analysis). Regarding to TGFβ isoforms, we found that Smad2 mRNA and TGFβ1 mRNA were inversely correlated (p = 0.05, R = -0.33), and that seven of the eight TGFβ1(+ )patients were Smad2(-). In larynx SCC, Smad7(- )patients did not reach mOS whereas mOS of Smad7(+ )patients were only 7.0 months (P = 0.04). No other correlations were found among Smad expression, clinico-pathological characteristics and survival in oral, larynx, hypopharynx, oropharynx or the entire head and neck SCC population. CONCLUSION: Smad6 together with Smad2 may be prognostic factors, independent of nodal status in oral SCC after curative resection. The underlying mechanism which involves aberrant TGFβ signaling should be better clarified in the future. BioMed Central 2010-05-12 /pmc/articles/PMC2885344/ /pubmed/20462450 http://dx.doi.org/10.1186/1476-4598-9-106 Text en Copyright ©2010 Mangone et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Mangone, Flavia RR Walder, Fernando Maistro, Simone Pasini, Fátima S Lehn, Carlos N Carvalho, Marcos B Brentani, M Mitzi Snitcovsky, Igor Federico, Miriam HH Smad2 and Smad6 as predictors of overall survival in oral squamous cell carcinoma patients |
title | Smad2 and Smad6 as predictors of overall survival in oral squamous cell carcinoma patients |
title_full | Smad2 and Smad6 as predictors of overall survival in oral squamous cell carcinoma patients |
title_fullStr | Smad2 and Smad6 as predictors of overall survival in oral squamous cell carcinoma patients |
title_full_unstemmed | Smad2 and Smad6 as predictors of overall survival in oral squamous cell carcinoma patients |
title_short | Smad2 and Smad6 as predictors of overall survival in oral squamous cell carcinoma patients |
title_sort | smad2 and smad6 as predictors of overall survival in oral squamous cell carcinoma patients |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885344/ https://www.ncbi.nlm.nih.gov/pubmed/20462450 http://dx.doi.org/10.1186/1476-4598-9-106 |
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