Downregulation of polo-like kinase 4 in hepatocellular carcinoma associates with poor prognosis.
Downregulation of polo-like kinase 4 in hepatocellular carcinoma associates with poor prognosis.
复制标题
肝细胞癌中 Polo 样激酶 4 的下调与不良预后相关
DOI：
10.1371/journal.pone.0041293
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Yun J
中科院分区：
文献类型：
--
作者：
Liu L;Zhang CZ;Cai M;Fu J;Chen GG;Yun J
Polo 样激酶 4 (PLK4) 属于丝氨酸/苏氨酸激酶家族，对于中心粒复制和细胞周期进展至关重要。 PLK4 已被提议作为肝细胞癌 (HCC) 的肿瘤抑制因子。然而，其在 HCC 中的表达和意义尚未得到充分研究。在本研究中，我们使用定量实时 PCR 和蛋白质印迹发现 PLK4 在 HCC 细胞系和新鲜癌症组织中显着下调。免疫组织化学数据还显示，与相应的邻近非肿瘤组织相比，72.4% (178/246) 的 HCC 组织中 PLK4 表达降低。此外，PLK4表达与临床病理参数显着相关，包括临床分期（P = 0.034）、血清甲胎蛋白（AFP）（P = 0.019）和肿瘤大小（P = 0.032）。此外，通过Kaplan-Meier法评估的总生存期（P = 0.002）和无病生存期（P = 0.012）表明，PLK4低表达的HCC患者的生存期短于PLK4高表达的患者。此外，多变量分析表明PLK4是总生存期（HR，0.556；95%CI，0.376−0.822；P = 0.003）和无病生存期（HR，0.547；95%CI，0.382−0.783；P = 0.001）的独立预测因子。总的来说，我们的研究表明 PLK4 在 HCC 中显着下调，可以作为患有这种致命疾病的患者的潜在预后标志物。
Polo-like kinase 4 (PLK4), belonging to serine/threonine kinase family, is critical for centriole replication and cell cycle progression. PLK4 has been proposed as a tumor suppressor in hepatocellular carcinoma (HCC). However, its expression and significance in HCC have not been well studied. In the present study, we found that PLK4 was markedly downregulated in both HCC cell lines and fresh cancer tissues, using quantitative real-time-PCR and western blot. Immunohistochemistry data also revealed that decreased expression of PLK4 was present in 72.4% (178/246) of HCC tissues, compared with the corresponding adjacent nontumorous tissues. Furthermore, PLK4 expression significantly correlated with clinicopathological parameters, including clinical stage (P = 0.034), serum α-fetoprotein (AFP) (P = 0.019) and tumor size (P = 0.032). Moreover, HCC patients with low PLK4 expression survived shorter than those with high PLK4 expression, as indicated by overall survival (P = 0.002) and disease-free survival (P = 0.012) assessed by the Kaplan–Meier method. In addition, multivariate analysis suggested PLK4 as an independent predictor of overall survival (HR, 0.556; 95%CI, 0.376−0.822; P = 0.003) and disease-free survival (HR, 0.547; 95%CI, 0.382−0.783; P = 0.001). Collectively, our study demonstrated that PLK4 was remarkably downregulated in HCC and could be served as a potential prognostic marker for patients with this deadly disease.
登录
查看更多内容
影响因子：
9.2
作者：
Eckerdt, Frank;Yamamoto, Tomomi M.;Maller, James L.
通讯作者：
Maller, James L.
影响因子：
21.3
作者：
Habedanck, R;Stierhof, YD;Nigg, EA
通讯作者：
Nigg, EA
DOI：
10.1073/pnas.91.14.6388
发表时间：
1994-07-05
影响因子：
11.1
作者：
FODE, C;MOTRO, B;DENNIS, JW
通讯作者：
DENNIS, JW
影响因子：
82.9
作者：
Kononen, J;Bubendorf, L;Kallioniemi, OP
通讯作者：
Kallioniemi, OP
DOI：
10.3350/kjhep.2010.16.3.308
发表时间：
2010-09
期刊：
The Korean journal of hepatology
影响因子：
--
作者：
Kwon OS;Jung YK;Kim YS;Kim SG;Kim YS;Lee JI;Lee JW;Kim YS;Chun BC;Kim JH
通讯作者：
Kim JH