Correlation of Activated STAT3 Expression with Clinicopathologic Features in Lung Adenocarcinoma and Squamous Cell Carcinoma
Correlation of Activated STAT3 Expression with Clinicopathologic Features in Lung Adenocarcinoma and Squamous Cell Carcinoma
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肺腺癌和鳞状细胞癌中活化的 STAT3 表达与临床病理特征的相关性
DOI：
10.2165/11599190-000000000-00000
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发表时间：
2011-01-01
影响因子：
4
通讯作者：
Li, Kai
中科院分区：
文献类型：
--
作者：
Jiang, Richeng;Jin, Ziliang;Li, Kai
背景和目的：信号转导和转录激活因子（STAT）3是Janus激酶（JAK）/STAT信号通路中STAT家族转录因子的成员，参与细胞增殖和凋亡。STAT 3通过磷酸化（p-STAT 3）被激活，并且在许多恶性肿瘤中高度表达。本研究旨在探讨肺腺癌和肺鳞癌组织中STAT 3的活化（p-STAT 3蛋白水平）及其与肺腺癌和肺鳞癌临床病理特征的关系。方法：采用免疫组化法检测127例肺癌组织（腺癌100例，鳞癌27例）和56例正常肺组织中p-STAT 3的表达。从冷冻的患者组织样本中提取基因组DNA，并扩增和测序EGFR基因外显子18至21中的关键表皮生长因子受体（EGFR）突变位点。结果：根据p-STAT 3免疫反应的强度和百分比，将样本分为阴性和阳性p-STAT 3表达组。这183个样品中的103个（56.3%）显示出p-STAT 3的免疫反应性，并且与正常组织相比，该频率在癌组织中显著增加（p = 0.001）。p-STAT 3在127例癌组织中的阳性表达率为64.6%（82/127），而在56例正常组织中的阳性表达率为37.5%（21/56）。在127例非小细胞肺癌中，p-STAT 3免疫反应性与性别显著相关（p = 0.004），吸烟史（p = 0.006），EGFR突变状态（p = 0.003），临床分期（p = 0.034），淋巴结转移（p = 0.009）。我们的研究结果提示p-STAT 3在肺癌的发生和转移过程中起重要作用，其与EGFR突变状态的关系可能为未来的治疗提供潜在的靶向机会。
Background and Objective: Signal transducer and activator of transcription (STAT) 3, a member of the STAT family of transcription factors in the Janus kinase (JAK)/STAT signaling pathway, is involved in cell proliferation and apoptosis. STAT3 is activated through phosphorylation (p-STAT3) and is highly expressed in many malignancies. The aims of the present study were to evaluate STAT3 activation (p-STAT3 protein levels) in lung adenocarcinoma and squamous cell carcinoma, and to investigate its correlation with clinicopathologic features of these malignancies.Methods: Expression of p-STAT3 was detected by immunohistochemistry in tissue from 127 lung carcinomas (100 adenocarcinomas and 27 squamous cell carcinomas) and 56 normal lungs. Genomic DNA was extracted from frozen patient tissue samples, and key epidermal growth factor receptor (EGFR) mutation sites in exons 18 through 21 of the EGFR gene were amplified and sequenced.Results: On the basis of the intensity and percentage of p-STAT3 immunoreactivity, samples were divided into negative and positive p-STAT3 expression groups. 103 of these 183 samples (56.3%) showed immunoreactivity for p-STAT3, and this frequency was significantly increased in carcinoma tissue compared with normal tissue (p = 0.001). Positive p-STAT3 expression was detected in 82 of the 127 carcinomas (64.6%) but in only 21 of the 56 normal tissue samples (37.5%). Among the 127 cases of non-small cell lung cancer, p-STAT3 immunoreactivity was significantly correlated with sex (p = 0.004), smoking history (p = 0.006), EGFR mutation status (p = 0.003), clinical stage (p = 0.034), and lymph node metastasis (p = 0.009).Conclusion: Our results suggest that p-STAT3 is an important factor during carcinogenesis and metastasis of lung carcinoma, and its relationship to EGFR mutation status may provide potential targeting opportunities in future therapies.