Sakabe Tomohiko, Azumi Junya, Umekita Yoshihisa, Toriguchi Kan, Hatano Etsuro, Hirooka Yasuaki, Shiota Goshi
Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Tottori University, Yonago, Japan.
Division of Organ Pathology, Department of Pathology, Faculty of Medicine, Tottori University, Yonago, Japan.
Anticancer Res. 2017 Sep;37(9):4881-4888. doi: 10.21873/anticanres.11897.
BACKGROUND/AIM: Cancer stem cells (CSCs) are associated with prognosis of hepatocellular carcinoma (HCC). In our previous study, we created cDNA microarray databases on the CSC population of human HuH7 cells. In the present study, we identified genes that might serve as prognostic markers of HCC by employing existing databases.
Expressions of glutathione S-transferase pi 1 (GSTP1), lysozyme (LYZ), C-X-C motif chemokine ligand 5 (CXCL5), interleukin-8 (IL8) and dickkopf WNT signaling pathway inhibitor 1 (DKK1), the five most highly expressed genes in the CSC cDNA microarray databases, were examined in 99 patients with HCC by real-time polymerase chain reaction (qRT-PCR), and their clinical significance was analyzed.
The Kaplan-Meier analysis showed that both overall and cancer-specific survival were significantly longer in patients with low DKK1 expression than in those with high DKK1 expression. The multivariate analysis revealed that overall survival was negatively associated with albumin and positively associated with alkaline phosphatase (ALP), serosal invasion and stage, and cancer-specific survival was positively associated with ALP, portal vein invasion and DKK1 mRNA.
Expression of CSC-associated DKK1 mRNA might be an unfavorable prognostic marker for patients with HCC.
背景/目的：癌症干细胞（CSCs）与肝细胞癌（HCC）的预后相关。在我们之前的研究中，我们创建了关于人HuH7细胞CSC群体的cDNA微阵列数据库。在本研究中，我们通过利用现有数据库鉴定了可能作为HCC预后标志物的基因。
通过实时聚合酶链反应（qRT-PCR）检测了CSC cDNA微阵列数据库中表达最高的五个基因，即谷胱甘肽S-转移酶pi 1（GSTP1）、溶菌酶（LYZ）、C-X-C基序趋化因子配体5（CXCL5）、白细胞介素-8（IL8）和Dickkopf WNT信号通路抑制剂1（DKK1）在99例HCC患者中的表达情况，并分析了其临床意义。
Kaplan-Meier分析显示，DKK1低表达患者的总生存期和癌症特异性生存期均显著长于DKK1高表达患者。多因素分析显示，总生存期与白蛋白呈负相关，与碱性磷酸酶（ALP）、浆膜侵犯和分期呈正相关，癌症特异性生存期与ALP、门静脉侵犯和DKK1 mRNA呈正相关。
CSC相关的DKK1 mRNA表达可能是HCC患者不良预后的标志物。
