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

Abstract

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.

Association of lung adenocarcinoma clinical stage with gene expression pattern in noninvolved lung tissue

“…SMAD6 (SMAD family member 6) encodes a signal transducer involved in different pathways, including BMP and TGF‐beta/activin signaling. In oral squamous cell carcinoma, patients with SMAD6‐negative tumors had a poor survival rate compared with patients with SMAD6‐positive tumors,10, 11 whereas opposite findings were reported for nonsmall cell lung cancer (NSCLC) 12. The reported reduced viability of lung cancer cell lines with knocked down SMAD6 expression12 contrasts with our findings of downregulated SMAD6 mRNA expression in lung ADCA (Fig.…”

Interferon Stimulated Gene - ISG15 is a Potential Diagnostic Biomarker in Oral Squamous Cell Carcinomas

“…Studies have revealed differential expression of several genes in OSCC lesions such as cyclin D1, EGFR, Tetranectin, NuclearS100A7, Smad2, Smad6, DeltaNp63 and PCD4, that have been proposed as potential biomarker to predict transforming potential of precancerous lesions and prognosis of well differentiated carcinomas (Ginos et al, 2004;O'Donnell et al, 2005;Saintigny et al, 2009;Arellano-Garcia et al, 2010;Mangone et al, 2010;Reis et al, 2010;Tripathi et al, 2010). However, none of the molecules have had an expression level similar to the findings of present study.…”

Epithelial to mesenchymal transition in head and neck squamous cell carcinoma

“…50 In HNSCC patient tumors, high expression of SMAD6 and low expression of SMAD2 correlated with better survival, whereas, low levels of SMAD7 correlated with decreased survival. 51 Taken together, these studies demonstrate that TGFβ1 promotes EMT through multiple mechanisms in HNSCC. 48 …”