Smad2 and Smad6 as predictors of overall survival in oral squamous cell carcinoma patients

Molecular Cancer

Research

Fernando Walder¹  Flavia RR Mangone²  Fátima S Pasini²  M Mitzi Brentani²  Igor Snitcovsky²  Simone Maistro²  Miriam HH Federico²  Marcos B Carvalho³  Carlos N Lehn³ 

[1] Departamento de Otorrinolaringologia, Universidade Federal de São Paulo, São Paulo, Brasil;Serviço de Cirurgia de Cabeça e Pescoço, Hospital Heliópolis, São Paulo, Brasil;Disciplina de Oncologia, Departamento de Radiologia, LIM 24, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Avenida Dr Arnaldo 455, São Paulo, Brasil;Serviço de Cirurgia de Cabeça e Pescoço, Hospital Heliópolis, São Paulo, Brasil;

关键词: Squamous Cell Carcinoma;    Oral Squamous Cell Carcinoma;    Oral Squamous Cell Carcinoma;    Oral Squamous Cell Carcinoma Patient;    Larynx Cancer;   

DOI  :  10.1186/1476-4598-9-106

 received in 2009-05-08, accepted in 2010-05-12,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundTo test if the expression of Smad1-8 mRNAs were predictive of survival in patients with oral squamous cell carcinoma (SCC).Patients and MethodsWe 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.ResultsOur 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.ConclusionSmad6 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.

【 授权许可】

CC BY   
© Mangone et al; licensee BioMed Central Ltd. 2010