Liu Bin, Ren Zhong, Shi Yang, Guan Chao, Pan Zimin, Zong Zhihong
Department of Otorhinolaryngology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
Laryngoscope. 2008 Nov;118(11):1976-80. doi: 10.1097/MLG.0b013e31817fd3fa.
OBJECTIVES/HYPOTHESIS: Constitutive activation of signal transducers and activators of transcription (STAT) 3 has been observed in many solid tumors including head and neck squamous cell carcinoma. Expression and activation of STAT3 in laryngeal carcinoma have not been fully understood. The study aims to investigate the expression and activation of STAT3 in laryngeal carcinoma, the relationship between activated STAT3 and its downstream target gene CyclinD1 and the related clinicopathological factors of activated STAT3.
Prospective.
Sixty-four samples of laryngeal squamous cell carcinoma and 12 samples of control mucosa obtained from total laryngectomy cases were analyzed using Western blot analysis and reverse transcriptase-polymerase chain reaction. Statistical analysis was performed using SPSS.
The overexpression of both STAT3 and CyclinD1 mRNA was observed in all samples of laryngeal squamous cell carcinoma. The mRNA levels of STAT3 and CyclinD1 in carcinoma tissue were 2.1- and 2.3-fold higher than those in control mucosa, respectively; the differences were statistically significant (P < .01). The overexpression of STAT3, p-STAT3, and CyclinD1 protein was also observed in all tumor samples. The protein levels of STAT3, p-STAT3, and CyclinD1 in carcinoma tissue were 1.6-, 4.5-, and 2.0-fold higher than those in control mucosa respectively; the differences were statistically significant (P < .01). There was a positive correlation between p-STAT3 protein and CyclinD1 mRNA (Pearson correlation coefficient = 0.827, P < .01). There were significant correlations between the overexpression of p-STAT3 protein and clinical T stage (P < .01), and tumor size (P < .05). The p-STAT3 protein level of patients in T1, T2 was higher than that of patients in T3, T4. The p-STAT3 protein level of patients with tumor size within 20 mm was higher than that of patients with tumor size more than 20 mm.
High expression and activation of STAT3 exist in laryngeal carcinomas. Activated STAT3 may take effect on promoting transcription of its downstream target gene CyclinD1. The role of activation of STAT3 in laryngeal carcinogenesis needs further research.
目的/假设：在包括头颈部鳞状细胞癌在内的许多实体瘤中都观察到信号转导和转录激活因子（STAT）3的组成性激活。喉癌中STAT3的表达和激活尚未完全明确。本研究旨在探讨喉癌中STAT3的表达和激活情况、激活的STAT3与其下游靶基因细胞周期蛋白D1（CyclinD1）之间的关系以及激活的STAT3相关的临床病理因素。
前瞻性研究。
采用蛋白质免疫印迹分析和逆转录聚合酶链反应，对64例喉鳞状细胞癌样本和12例全喉切除病例的对照黏膜样本进行分析。使用SPSS进行统计学分析。
在所有喉鳞状细胞癌样本中均观察到STAT3和CyclinD1 mRNA的过表达。癌组织中STAT3和CyclinD1的mRNA水平分别比对照黏膜高2.1倍和2.3倍；差异具有统计学意义（P <.01）。在所有肿瘤样本中也观察到STAT3、磷酸化STAT3（p-STAT3）和CyclinD1蛋白的过表达。癌组织中STAT3、p-STAT3和CyclinD1的蛋白水平分别比对照黏膜高1.6倍、4.5倍和2.0倍；差异具有统计学意义（P <.01）。p-STAT3蛋白与CyclinD1 mRNA之间存在正相关（Pearson相关系数 = 0.827，P <.01）。p-STAT3蛋白的过表达与临床T分期（P <.01）和肿瘤大小（P <.05）之间存在显著相关性。T1、T2期患者的p-STAT3蛋白水平高于T3、T4期患者。肿瘤大小在20 mm以内的患者的p-STAT3蛋白水平高于肿瘤大小超过20 mm的患者。
喉癌中存在STAT3的高表达和激活。激活的STAT3可能对促进其下游靶基因CyclinD1的转录起作用。STAT3激活在喉癌发生中的作用需要进一步研究。
