Second Department of Surgery, Wakayama Medical University, Wakayama, Japan.
Cbs Bioscience, Inc, Daejeon, Korea.
J Surg Res. 2020 Jan;245:302-308. doi: 10.1016/j.jss.2019.07.077. Epub 2019 Aug 14.
Epithelial-mesenchymal transition genes have prognostic influence on hepatocellular carcinoma (HCC). Previously, the following four epithelial-mesenchymal transition-related genes were considered to be significantly influential: E-cadherin (CDH1), inhibitor of DNA binding 2 (ID2), matrix metalloproteinase 9 (MMP9), and transcription factor 3 (TCF3). A prognostic prediction model, NRISK4 = (-0.333 × [CDH1] - 0.400 × [ID2] + 0.339 × [MMP9] + 0.387 × [TCF3]) was constructed, but from patients with HCC with predominantly hepatitis B virus infection. We therefore aim to validate if this model also fits patients with HCC and hepatitis C virus (HCV) infection.
We collected HCC tissue samples from 67 patients with HCV infection. Discrimination of the NRISK4 was re-estimated using receiver operating curve analysis and we redefined the appropriate cutoff value. Using this cutoff value, patients were divided into two groups (high/low risk patients) and we compared their clinicopathological factors and prognosis.
Area under the curve of NRISK4 prediction was 0.70 and an appropriate cutoff value was 3.19 in this cohort. Patients were divided into high- (n = 25) and low-risk (n = 42) patients for prognosis. There were no significant differences in tumor factors between the two groups. Cancer-specific survival rates at 5 y after surgery on high- and low-risk patients were 45% and 68%, respectively (P = 0.02). At 2 y after surgery, recurrence rates were 68% and 37% among high- and low-risk patients, respectively (P = 0.01). Aggressive recurrences were highly observed in the high-risk patients (P = 0.01).
NRISK4 model could also successfully validate prognosis of patients with HCC with HCV infection similarly to in the previous report of patients with hepatitis B virus infection, especially in the early period after surgery.
上皮-间充质转化基因对肝细胞癌（HCC）有预后影响。此前，以下四个上皮-间充质转化相关基因被认为具有显著影响：E-钙黏蛋白（CDH1）、DNA 结合抑制因子 2（ID2）、基质金属蛋白酶 9（MMP9）和转录因子 3（TCF3）。构建了一个预后预测模型 NRISK4 =（-0.333×[CDH1]-0.400×[ID2]+0.339×[MMP9]+0.387×[TCF3]），但该模型来自于主要感染乙型肝炎病毒的 HCC 患者。因此，我们旨在验证该模型是否也适用于丙型肝炎病毒（HCV）感染的 HCC 患者。
我们收集了 67 例 HCV 感染的 HCC 组织样本。使用接收者操作特征曲线分析重新估计 NRISK4 的区分能力，并重新定义了适当的截止值。使用该截止值，将患者分为两组（高/低危患者），并比较其临床病理因素和预后。
该队列中，NRISK4 预测的曲线下面积为 0.70，适当的截止值为 3.19。将患者分为高风险（n=25）和低风险（n=42）两组进行预后比较。两组间肿瘤因素无显著差异。高、低危患者术后 5 年的癌症特异性生存率分别为 45%和 68%（P=0.02）。术后 2 年，高、低危患者的复发率分别为 68%和 37%（P=0.01）。高危患者的复发率较高（P=0.01）。
NRISK4 模型也可以成功验证 HCV 感染 HCC 患者的预后，与乙型肝炎病毒感染患者的先前报告相似，尤其是在术后早期。
