Coexpression of Stemness Factors Oct4 and Nanog Predict Liver Resection
Coexpression of Stemness Factors Oct4 and Nanog Predict Liver Resection
复制标题
干细胞因子 Oct4 和 Nanog 的共表达预测肝切除
DOI：
10.1245/s10434-012-2314-6
复制
发表时间：
2012-09-01
影响因子：
3.7
通讯作者：
Fan, Jia
中科院分区：
文献类型：
--
作者：
Yin, Xin;Li, Yi-Wei;Fan, Jia
Oct4和Nanog是与干细胞自我更新和分化相关的两个主要转录因子。本研究的目的是评估这两种干性标志物与肝细胞癌 (HCC) 复发、转移和预后之间的相关性。通过免疫组织化学在 228 名 HCC 患者（主要与乙型肝炎相关）组成的随机队列中评估 Oct4 和 Nanog 的表达，并在另一个由 95 名患者组成的独立队列（B 队列）中进行验证。通过单变量和多变量分析进行生存分析。通过蛋白质印迹法和定量实时 PCR 法检测 5 种不同转移潜能的 HCC 细胞系中 Oct4 和 Nanog 的表达水平。在组织微阵列中，Oct4 和 Nanog 的共表达与肿瘤大小 (P = .001) 和血管侵犯 (P = .02) 显着相关，并且是术后复发的独立预测因子（风险比 [HR] = 1.57，95 % 置信区间 [95 % CI] 1.21-2.04，P = .01），预后不良（HR = 2.20，95 % CI 1.71-2.88，P < .001）。这种相关性在队列 B 的患者中得到了进一步验证。重要的是，这种相关性在早期 HCC 或甲胎蛋白 (AFP) 阴性 HCC 患者中仍然显着。此外，在人HCC细胞系中，Oct4和Nanog的表达随着转移潜能的增加而增加。干细胞标记物Oct4和Nanog在HCC中的共表达表明了肿瘤的侵袭性行为并预测了更差的临床结果，这可能是识别术后复发高风险患者的有用生物标志物。
Oct4 and Nanog are two major transcription factors related to the stem cell self-renewal and differentiation. The aim of this study was to evaluate the correlation between these two stemness markers with recurrence, metastasis, and prognosis of hepatocellular carcinoma (HCC).Expression of Oct4 and Nanog was evaluated by immunohistochemistry in a random cohort of 228 HCC patients (cohort A), predominantly hepatitis B related, and validated in another independent cohort of 95 patients (cohort B). Survival analysis was performed by univariate and multivariate analyses. Oct4 and Nanog expression levels in 5 HCC cell lines with different metastatic potential were detected by Western blot assay and quantitative real-time PCR assay.In tissue microarrays, coexpression of Oct4 and Nanog was dramatically associated with big tumor size (P = .001) and vascular invasion (P = .02) and was an independent predictor of postoperative recurrence (hazard ratio [HR] = 1.57, 95 % confidence interval [95 % CI] 1.21-2.04, P = .01) and poor prognosis (HR = 2.20, 95 % CI 1.71-2.88, P < .001). This association was further validated in patients in cohort B. Importantly, this correlation remained significant in patients with early-stage HCC or alpha-fetoprotein (AFP) negative HCC. In addition, expression of Oct4 and Nanog increased in a concordant manner with the increase of metastatic potential in human HCC cell lines.Coexpression of stemness markers Oct4 and Nanog in HCC indicated the aggressive tumor behaviors and predicted a worse clinical outcome, which may be a useful biomarker to identify patients at high risk of postoperative recurrence.