HIPK2在口腔鳞状细胞癌中的胞质再定位表达及其与预后的关系

Cytoplasmic Relocalization of HIPK2 and Its Relationship to the Prognosis of Oral Squamous Cell Carcinoma

目的：探讨同源结构域相互作用蛋白激酶2（HIPK2）在口腔鳞状细胞癌（OSCC）中的表达及其与预后的关系。方法：采用组织微阵及免疫组化染色方法检测99例OSCC组织中HIPK2的表达,利用real-time PCR及细胞免疫荧光实验检测OSCC细胞系中HIPK2基因和蛋白表达水平。结果：HIPK2在99例OSCC组织的肿瘤中心、肿瘤前沿及淋巴结转移灶中表达显著高于癌旁正常上皮（P〈0.05）;肿瘤中心伴淋巴结转移比不伴淋巴结转移的表达低（P〈0.000 1）。HIPK2具有胞核阳性、胞核及胞质均阳性及仅胞质阳性3种表达模式,癌旁正常上皮主要表现为胞核阳性;肿瘤主要表现为胞核及胞质均阳性或仅胞质阳性。HIPK2的表达模式与患者临床分期及病理分级显著相关（P〈0.01）,而与性别及年龄无显著相关性（P〉0.05）。OSCC的总体生存率与HIPK2的表达模式有关,胞核及胞质均阳性、仅胞质阳性相对较强、仅胞质阳性相对较弱者的总体生存率依次降低（P=0.000 6）。HIPK2在OSCC细胞系中mRNA及蛋白的表达显著高于正常上皮细胞系（HIOEC）（P〈0.01）。结论：HIPK2在OSCC中表达升高,且以仅胞质阳性表达为主。HIPK2的表达及胞质再定位与OSCC的预后密切相关。

Objective： To explore the expression of HIPK2 in oral squamous cell carcinoma （OSCC） and its relationship to the prognosis of OSCC. Methods： The expression of HIPK2 in 99 OSCC tissues was detected by mieroarrays and immunohistochemisty （IHC）. The gene and protein expression levels of HIPK2 in the OSCC cell lines cence experiments. Results： Compared were examined by real-time PCR and cell immunofluores- with that in adjacent normal epithelium, the expression of HIPK2 was significantly upregulated in primary tumors, tumor fronts and lymphatic metastatic lesions（P〈0.05）. Levels of HIPK2 were lower in primary tumors that subsequently metasta- sized than those without metastases （P〈0. 000 1）. There were three expression patterns of HIPK2 including positive nucleus, positive both nucleus and cytoplasm, and only positive cyto- plasm. The main positive location of normal epithelium cells was nucleus, while tumor cells were positive in both nucleus and cytoplasm or only cytoplasm. The expression pattern of HIPK2 was significantly related to clinical stages and pathological grades of patients（P〈0.01）, but did not significantly correlate to gender and age（P〈0.05）. The HIPK2 expression patterns was also as- sociated with the overall survival of OSCC, of which, positive nucleus pattern, positive both nu- cleus and cytoplasm pattern, and only positive cytoplasm pattern was decreased in turn（P=0. 000 6）. The mRNA and protein expression levels of HIPK2 in OSCC cell lines were significantly higher than those in normal epithelial cell line（P%0.01）. Conclusion： HIPK2 expression is significantly elevated in OSCC and the main expression pattern is positive cytoplasm. The expression of HIPK2 and its cytoplasmic relocalization have strong relationship with the prognosis of OSCC.