Background and objective: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
背景与目的: 通过检测宣威肺腺癌细胞株（XWLC-05）中甲状腺转录因子（thyroid transcription factor 1, TTF-1）mRNA和蛋白表达及宣威肺腺癌标本组织TTF-1和Ki-67蛋白的表达，分析宣威肺腺癌中TTF-1与Ki-67表达相关性及对患者预后的影响。
方法: 利用qRT-PCR方法检测XWLC-05中TTF-1 mRNA和免疫组化分析TTF-1及Ki-67蛋白表达。同时收集2008年1月-2012年3月96例手术后宣威肺腺癌组织标本，免疫组化检测TTF-1及Ki-67的蛋白表达。
结果: XWLC-05中TTF-1 mRNA低表达，免疫组化TTF-1表达阴性，Ki-67 100%表达。96例肺癌患者TNM分期Ⅰ期-Ⅱ期66%（63/96）、Ⅲ期34%（33/96），TTF-1蛋白表达率93%（89/96），Ki-67为70%（67/96)，其中高分化腺癌TTF-1阳性表达率98%（31/39)，中低分化腺癌89%（51/57)。TTF-1阳性表达随着分化程度的增加而增高（P=0.002），与Ki-67的表达负相关（P=0.01），与性别、年龄、吸烟史及分期无关。Kaplan-Meier生存曲线显示患者中位无进展生存（median progression-free survival, PFS）与分期、TTF-1及Ki-67表达强度有关，Ⅰ期-Ⅱ期PFS高于Ⅲ期（46个月vs 32个月，P=0.001），TTF-1强阳性高于弱阳性和阴性组（45个月vs 35个月，P=0.036），Ki-67弱阳性和阴性高于强阳性组（46个月vs 40个月，P=0.048）。
结论: TTF-1在肺腺癌中可能是一个肿瘤抑制基因，基于它能抑制Ki-67的表达，并且可作为宣威肺腺癌好的预后指标。