Transforming growth factor-β1 and α-smooth muscle actin in stromal fibroblasts are associated with a poor prognosis in patients with clinical stage I–IIIA nonsmall cell lung cancer after curative resection

The aims of this study were to investigate the expression of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) in surgical resection specimens from nonsmall cell lung cancer (NSCLC) and to evaluate the prognostic significance of this gene expression in stromal fibroblasts for patients with clinical stage I–IIIA NSCLC. The immunohistochemical expression of TGF-β1 and α-SMA was evaluated in 78 formalin-fixed paraffin-embedded tumor specimens from clinical stage I–IIIA NSCLC. Correlations between this gene expression and the clinicopathologic characteristics were determined by chi-square test. The prognostic impact of this gene expression in stromal fibroblasts with regard to overall survival (OS) was determined by Kaplan-Meier and Cox hazard proportional model. The percentages of high TGF-β1 expression in stromal fibroblasts and cancer cells were 19.2 % (15/78) and 35.9 % (28/78), respectively. There were 28.2 % (22/78) of patients with high α-SMA expression in stromal fibroblasts. The analysis revealed a significant positive association between TGF-β1 expression in stromal fibroblasts and in cancer cells (χ ² = 4.86, p = 0.03). No significant association was found between TGF-β1 in cancer cells and α-SMA expression in stromal fibroblasts (χ ² = 0.978, p = 0.326). The 3-year OS rates with low and high TGF-β1 expression in stromal fibroblasts were 52.4 and 26.7 %, respectively (χ ² = 5.42, p = 0.019). The 3-year OS rates with low and high α-SMA expression in stromal fibroblasts were 53.9 and 31.0 %, respectively (χ ² = 5.01, p = 0.025). The multivariate analysis revealed that clinical stage and TGF-β1 and α-SMA expression levels in stromal fibroblasts were identified as independent predictive factors of OS. The results suggest that the expression level of TGF-β1 and α-SMA in stromal fibroblasts may have prognostic significance in patients with clinical stage I–IIIA NSCLC after curative resection.