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甲状腺转录因子1在宣威肺腺癌中的表达及临床意义

[Expression and clinical significance of the thyroid transcription factor 1 in Xuanwei lung adenocarcinoma].

作者信息

Zu Yunfen, Wang Xicai, Liu Xin, Chen Yan, Li Chengwen, Shang Xueqin, Xie Yucheng, Zhao Hongyuan, Wang Jiying

机构信息

Department of Oncology, the Second People Hospital of Yunnan Province, Kunming 650021, China.

出版信息

Zhongguo Fei Ai Za Zhi. 2013 Mar;16(3):131-7. doi: 10.3779/j.issn.1009-3419.2013.03.03.

Abstract

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.

摘要

背景与目的

本研究旨在检测甲状腺转录因子1(TTF-1)mRNA和蛋白在宣威肺腺癌系(XWLC-05)中的表达情况。我们还研究了TTF-1与Ki-67蛋白的关系,并分析了TTF-1蛋白在宣威肺腺癌患者中的预后价值。

方法

采用定量实时逆转录聚合酶链反应(qRT-PCR)评估TTF-1 mRNA的表达,采用免疫组织化学法检测XWLC-05中TTF-1和Ki-67蛋白。2008年1月至2012年3月,采用免疫组织化学法检测96例手术切除的宣威肺腺癌病例中TTF-1和Ki-67的表达。

结果

XWLC-05中TTF-1 mRNA水平低且无蛋白表达。XWLC-05中Ki67蛋白表达为100%(高增殖活性)。所有样本均为宣威肺腺癌(n = 96),TNM分期I-II期占66%(63/96),III期占34%(33/96)。免疫组织化学分析显示,96例中有89例(93%)表达TTF-1,96例中有69例(70%)表达Ki-67。高分化表型的39例中有38例(96%)TTF-1蛋白呈阳性,中/低分化表型的57例中有51例(89%)呈阳性。TTF-1免疫组织化学强表达患者与高分化表型具有统计学相关性(P = 0.002),与Ki-67表达呈负相关(P = 0.01),与年龄、性别、吸烟史和分期无关。Kaplan-Meier生存分析结果显示,TTF-1和Ki-67分期与宣威肺腺癌患者的预后显著相关。I-II期、TTF-1强阳性表达且Ki-67阴性和弱阳性表达组患者的无进展生存期中位数显著高于III期患者(46个月对32个月,P = 0.001)、TTF-1阴性和弱阳性表达患者(45个月对35个月,P = 0.036)以及Ki-67强阳性表达组患者(46个月对四十个月,P = 0.048)。

结论

我们的研究结果表明,基于TTF-1与Ki-67增殖活性呈负相关,TTF-1可能作为一种肿瘤抑制基因。在宣威肺腺癌中,TTF-1蛋白强表达组患者的预后明显优于TTF-1蛋白阴性和弱阳性表达组患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de80/6015132/bac52344cae8/zgfazz-16-3-131-1.jpg

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