DAPK1在甲状腺乳头状癌中的表达及意义

Expression of death-associated protein kinase 1 in papillary thyroid carcinoma

背景与目的:死亡相关蛋白激酶(DAPK1)是凋亡的正性调节因子之一,在肿瘤的发生发展中具有重要作用。本研究通过检测甲状腺乳头状癌组织和相应的癌旁组织中DAPK1 mRNA表达及细胞凋亡情况,探讨DAPK1与细胞凋亡的关系及其在甲状腺乳头状癌发生发展中的作用。方法:本研究采用45例由癌及癌旁组织组成的配对甲状腺癌乳头状标本,其中癌旁组织的病理类型分别为:正常甲状腺、结节性甲状腺肿、滤泡状腺瘤,各15例,每例取癌及癌旁组织各一份,分别行连续切片。用原位杂交法检测DAPK1 mRNA表达;用原位末端标记(TUNEL)法检测相应组织中细胞凋亡,计算凋亡指数(AI)。结果:甲状腺乳头状癌组织中的DAPK1 mRNA阳性表达率和AI分别为37.78%(17/45),(0.74±0.30)%;癌旁组织中为71.11%(32/45),(1.39±0.29)%。两者在癌旁组织中的表达均显著高于癌组织(P<0.01)。癌组织中DAPK1 mRNA呈阳性表达者,其AI为(0.94±0.22)%;表达阴性者,其AI为(0.62±0.28)%,两者间差异有非常显著性(P<0.001)。在连续切片上,DAPK1mRNA阳性细胞的分布区域与凋亡阳性细胞的分布相似。淋巴结癌转移阳性的癌组织DAPK1 mRNA阳性表达率低于淋巴结转移阴性的病例(17.65%vs 50%,P<0.05)。DAPK1的表达与患者的年龄、性别、肿瘤大小、周围浸润情况无关(P>0.05)。结论:DAPK1有肿瘤抑制作用,其表达低下或缺失可能参与了甲状腺乳头状癌的发生发展过程。检测DAPK1表达水平可作为判断甲状腺乳头状癌转移和预后的参考指标。

Background and purpose： Death-associated protein kinase-1 （DAPK） is a pro-apoptosis protein, and plays a important role in oncagenesis and development . This study is to investigate the expression of mRNA of DAPK1 and its association with apoptosis in papillary thyroid carcinoma（PTC）. Methods： The expression of DAPK1 mRNA was detected by in situ hybridization in 45 cases of PTC and 45 cases of normal thyroid tissues next to tumors that consist of three part of tissue： normal thyroid tissue, nodular goiter and follicular adenoma. The apoptosis in corresponding issues was tested by TUNEL assay and the apoptosis index （AI） was evaluated. Results： The positive rate of DAPK1mRNA in PTC and para-PTC tissues were 37.78% and 71.11% , respectively. The positive rate of DAPK1 mRNA in counterpart thyroid issues was higher than that in tumor tissues （P 〈0.01）. The AI in PTC was （0.74±0.30） %, compared to （1.39±0. 29）% in counteqoart thyroid issues （P 〈0. 001）. The AI in normal thyroid issue was （ 1.35± 0.28） %, （ 1.36 ± 0. 24） % in nodular goiter and （ 1.46 ± 0. 34） % in thyroid adenoma. The AI of PTC with DAPK1 mRNA positive was （0. 94 ±0.22） % ; compared to the tumor with DAPK1 mRNA negative was （0. 62 ± 0.28）%, P 〈0.001. On continuous sections, the distribution of DAPKlmRNA positive cells was similar to cells in which the apoptosis was evident. The positive rate of DAPK1mRNA expression in the cases with lymph node involvement was lower than that without lymph node involvement （P 〈 0.05）. The expression of DAPK1 mRNA was not associated with the age, sex, or tumor size of the patlents（P 〉0.05）. Conclusions： As an apoptosis promoter, DAPK1 may function as an inhibitor of tumor, and low expression or loss DAPK1 gene may be involved in the oncogenesis of PTC. The detection of the expression of DAPK1 may be helpful for judging metastasis and prognosis of PTC.