International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, the Second Military Medical University, Shanghai, China; National Center for Liver Cancer, Shanghai, China; Department of Liver Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
Cancer. 2014 May 15;120(10):1520-31. doi: 10.1002/cncr.28593. Epub 2014 Feb 22.
The functions of cytoskeleton-associated membrane protein 4 (CKAP4), one kind of type II transmembrane protein, are associated with the palmitoyl acyltransferase DHHC2. The objective of the current study was to investigate CKAP4/DHHC2 expression and its prognostic significance in patients with hepatocellular carcinoma (HCC).
Two independent cohorts of 416 patients with HCC were enrolled. All the patients included had defined clinicopathologic and follow-up data. Using real-time polymerase chain reaction and immunohistochemical assay, CKAP4 and DHHC2 expression were evaluated. The association between CKAP4/DHHC2 expression and HCC-specific disease-free survival and overall survival was analyzed by Kaplan-Meier curves, the log-rank test, and Multivariate Cox regression analyses.
The data documented that CKAP4 expression was much higher in HCC tumor tissues compared with adjacent normal tissues and its expression was significantly correlated with tumor size, intrahepatic metastases, portal venous invasion, and Barcelona Clinic Liver Cancer stage of disease in 2 cohorts of patients. On survival analysis, patients with high CKAP4 expression appeared to have a favorable overall survival and a longer disease-free survival compared with those with low expression. DHHC2 expression was also examined in tissue microarray analysis by immunohistochemistry and the results demonstrated that 87.6% of the cases had low expression of DHHC2. Kaplan-Meier analysis indicated that a high level of DHHC2 expression predicted favorable overall survival and disease-free survival rates in both the training cohort and validation set. Furthermore, the combination of CKAP4 and DHHC2 was found to have a more powerful efficiency in prognosis prediction than either one alone.
To the best of our knowledge, the current study is the first to demonstrate that the expression of CKAP4 and its palmitoyl acyltransferase DHHC2 correlates with disease progression and metastasis in patients with HCC and may provide prognostic and therapeutic value.
细胞骨架相关膜蛋白 4（CKAP4）是一种 II 型跨膜蛋白，其功能与棕榈酰转移酶 DHHC2 相关。本研究旨在探讨 CKAP4/DHHC2 的表达及其在肝细胞癌（HCC）患者中的预后意义。
本研究纳入了 416 例 HCC 患者的两个独立队列，所有患者均具有明确的临床病理和随访资料。采用实时聚合酶链反应和免疫组织化学检测 CKAP4 和 DHHC2 的表达。通过 Kaplan-Meier 曲线、对数秩检验和多因素 Cox 回归分析，分析 CKAP4/DHHC2 表达与 HCC 特异性无病生存和总生存的关系。
数据显示，CKAP4 在 HCC 肿瘤组织中的表达明显高于相邻正常组织，且其表达与肿瘤大小、肝内转移、门静脉侵犯和巴塞罗那临床肝癌分期显著相关。生存分析显示，CKAP4 高表达组患者的总生存和无病生存均优于 CKAP4 低表达组。通过免疫组织化学方法在组织微阵列分析中检测 DHHC2 表达，结果显示 87.6%的病例 DHHC2 表达较低。Kaplan-Meier 分析表明，DHHC2 高表达预示着训练队列和验证队列的总生存和无病生存率均较好。此外，CKAP4 和 DHHC2 的联合表达比单独一种表达具有更强的预后预测能力。
据我们所知，本研究首次证明 CKAP4 的表达及其棕榈酰转移酶 DHHC2 与 HCC 患者的疾病进展和转移相关，可能具有预后和治疗价值。
