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The thyroid transcription factor 1 (TTF-1) gene is associated with the differentiation of lung epithelial cells and has been reported to be an independent prognostic factor for lung adenocarcinoma patients. The aim of the present study was to detect the expression of TTF-1 in human lung cancer cell lines and to evaluate the association of overexpressed TTF-1 with Ki-67 and apoptosis in the A549 cell line. We also investigated the expression of TTF-1 and Ki-67 in Xuanwei lung adenocarcinoma. TTF-1 mRNA expression was evaluated in 10 non-small cell lung cancer (NSCLC) cell lines by quantitative real-time RT-PCR (qRT-PCR). Overexpression of TTF-1 in A549 cells was achieved by transient transfection. The TTF-1 and Ki-67 proteins were detected by immunohistochemistry and apoptosis was detected by flow cytometry. We also investigated immunohistochemically the expression of TTF-1 and Ki-67 in 62 resected cases of Xuanwei lung adenocarcinoma. Overall the expression of TTF-1 mRNA in the 10 cell lines was low. Overexpression of TTF-1 mRNA was found only in 3 (30%) of 10 NSCLC cell lines, including 1 (25%) of 4 adenocarcinoma cell lines. A549 cells overexpressing TTF-1 were found to have repressed expression of Ki-67 (P=0.012) and increased apoptosis (P=0.000). Immunohistochemical analysis of resected cases of Xuanwei lung adenocarcinoma (n=62) showed the expression of TTF-1 in 58 (93%) of 62 and Ki-67 in 22 (35%) of 62. Patients with strong immunohistochemical expression TTF-1 were statistically associated with well-differentiated phenotype (P=0.006) and inverse correlation with Ki-67 expression (P=0.016). These data suggest that TTF-1 may serve as a tumor suppressor gene based on its inverse correlation with Ki-67 proliferative activity and increase of cellular apoptosis.

The present study aims to detect the expressions of the thyroid transcription factor 1 (TTF-1) mRNA and protein in Xuanwei lung adenocarcinoma line (XWLC-05). We also investigated the relationship of TTF-1 with Ki-67 protein and analyzed the prognostic value of the TTF-1 protein in Xuanwei lung adenocarcinoma patients.The expression of TTF-1 mRNA was evaluated by quantitative real-time RT-PCR (qRT-PCR), while proteins of TTF-1 and Ki-67 were detected by immunohistochemistry in XWLC-05. The expressions of TTF-1 and Ki-67 was detected in 96 resected cases of Xuanwei lung adenocarcinoma by immunohistochemistry from January 2008 to March 2012.TTF-1 mRNA was low and protein was absent in XWLC-05. The expression of Ki67 protein was 100% (high proliferative activity) in XWLC-05. All samples were Xuanwei lung adenocarcinoma (n=96) and TNM stages were I-II 66% (63/96) and III 34% (33/96). Immunohistochemical analysis showed the expression of TTF-1 in 89 (93%) of 96 and Ki-67 in 69 (70%) of 96. The positive rate of TTF-1 protein was 38 (96%) of 39 in well-differentiated phenotype and 51 (89%) 57 in moderately/poorly-differentiated phenotype. Patients with strong immunohistochemical expression of TTF-1 were statistically associated with well-differentiated phenotype (P=0.002), has inverse correlation with Ki-67 expression (P=0.01), and no correlation with age, sex, smoking history, and stages. The result from the Kaplan-Meier survival analysis showed that stages TTF-1 and Ki-67 were significantly associated with the prognosis of Xuanwei lung adenocarcinoma patients. The median progression-free survival in patients with I-II stages, strong positive expression TTF-1 and negative, and weak expressions Ki-67 groups was remarkably higher than those patients with III stage (46 months vs 32 months, P=0.001), negative and weak expressions TTF-1 (45 months vs 35 months, P=0.036) and strong positive expression Ki-67 groups (46 months vs 40 months, P=0.048), respectively.Our results presented here suggest that TTF-1 may serve as a tumor suppressor gene based on its inverse correlation with Ki-67 proliferative activity. Patients with strong TTF-1 protein expression group tend to have a significantly better prognosis than patients with negative and weak TTF-1 protein expression group in Xuanwei lung adenocarcinoma.