Liu Yifei, Qian Li, Yang Juanjuan, Huang Hua, Feng Jia, Li Xiaoli, Bian Tingting, Ke Honggang, Liu Jian, Zhang Jianguo
Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China,
Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
Onco Targets Ther. 2018 Oct 25;11:7459-7469. doi: 10.2147/OTT.S166878. eCollection 2018.
Lung cancer is one of the most common malignancies in the world and is at the forefront of causes of all cancer deaths. Identification of new prognostic predictors or therapeutic targets might improve a patient's survival rate.
The Homeodomain interacting protein kinases (HIPKs) function as modulators of cellular stress responses and regulate cell differentiation, proliferation and apoptosis, but the function of HIPK3 is remain unknown.
We used quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting methods to detective the expression of HIPK3. A total of 206 samples were obtained from patients and Immunochemical evaluation to determine HIPK3 protein expression. HIPK3 protein levels in in non-small cell lung cancer (NSCLC) were correlated with the clinical characteristics of patients and their 5-year survival rate. In addition, HIPK3 knockdown by specific RNAi promoted cell proliferation, migration, and invasion in A549 and HCC827 cancer cell lines.
The quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting methods to demonstrate that HIPK3 expression was significantly down-regulated in non-small cell lung cancer (NSCLC) tissues compared with that in normal lung tissues. At the same time, the results of immunohistochemistry assays showed that low expression of HIPK3 was significantly associated with pathology grade; tumor, node, and metastases (TNM) stage; lymph node metastasis; Ki-67 expression; and the 5-year survival rate in NSCLC patients. Univariate analysis revealed that HIPK3 expression, Ki-67 expression, tumor diameter, TNM stage, and age were significantly associated with a poor prognosis. The multivariable analysis illustrated that HIPK3, tumor diameter, TNM, Ki-67 expression, and age had effects on the overall survival of NSCLC patients independently. Kaplan-Meier survival curves revealed that NSCLC patients with a lower HIPK3 expression had a poorer prognosis. In addition, in vivo results also confirmed that HIPK3 over-expression could inhibit tumor growth.
Our findings confirmed that low expression of HIPK3 in NSCLC tissues was significantly correlated with poor survival rates after curative resection. HIPK3 could potentially be used as a valuable biomarker in the prognosis of the survival of NSCLC patients.
肺癌是世界上最常见的恶性肿瘤之一，在所有癌症死亡原因中位居前列。识别新的预后预测指标或治疗靶点可能会提高患者的生存率。
同源结构域相互作用蛋白激酶（HIPKs）作为细胞应激反应的调节因子，调节细胞分化、增殖和凋亡，但HIPK3的功能尚不清楚。
我们使用定量实时聚合酶链反应（qRT-PCR）和蛋白质印迹法检测HIPK3的表达。从患者中获取了总共206个样本，并通过免疫化学评估来确定HIPK3蛋白表达。非小细胞肺癌（NSCLC）中HIPK3蛋白水平与患者的临床特征及其5年生存率相关。此外，通过特异性RNAi敲低HIPK3可促进A549和HCC827癌细胞系的细胞增殖、迁移和侵袭。
定量实时聚合酶链反应（qRT-PCR）和蛋白质印迹法表明，与正常肺组织相比，非小细胞肺癌（NSCLC）组织中HIPK3表达明显下调。同时，免疫组织化学分析结果显示，HIPK3低表达与病理分级、肿瘤、淋巴结和转移（TNM）分期、淋巴结转移、Ki-67表达以及NSCLC患者的5年生存率显著相关。单因素分析显示，HIPK3表达、Ki-67表达、肿瘤直径、TNM分期和年龄与预后不良显著相关。多变量分析表明，HIPK3、肿瘤直径、TNM、Ki-67表达和年龄独立影响NSCLC患者的总生存期。Kaplan-Meier生存曲线显示，HIPK3表达较低的NSCLC患者预后较差。此外，体内结果也证实HIPK3过表达可抑制肿瘤生长。
我们的研究结果证实，NSCLC组织中HIPK3低表达与根治性切除术后生存率低显著相关。HIPK3有可能作为NSCLC患者生存预后的有价值生物标志物。
