Bai Tao, Mai Rongyun, Ye Jiazhou, Chen Jie, Qi Lunan, Tang Juan, Wei Meng, Zhang Lianda, Chen Zhiwei, Tang Zhihong, Li Lequn, Wu Feixiang
Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, China.
Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning 530021, China.
Transl Cancer Res. 2020 Mar;9(3):1384-1394. doi: 10.21037/tcr.2020.01.14.
This study was to determine circulating tumor cells (CTCs) and the expression of CXC chemokine receptor type 4 (CXCR4) in primary hepatocellular carcinoma (HCC) and the relationships with prognosis.
We used an advanced CanPatrol CTC-enrichment technique to collect CTCs for isolation and characterization from blood samples. The RNA in situ hybridization (RNA-ISH) method, which is based on branched DNA (bDNA) signal amplification technology, was used to determine the expression of CXCR4 according to epithelial-mesenchymal transition (EMT) markers in 99 patients with primary liver cancer in blood samples pre-operatively. The relationship between the EMT markers and HCC was determined.
The positive rates of CTCs and CXCR4 were 89.9% and 58.8%, respectively. CTCs were positively correlated with the Barcelona clinic liver cancer (BCLC) staging, tumor diameter and number, envelope, microsatellite damage, portal vein thrombosis, alpha-fetoprotein (AFP), and hepatitis B DNA, and negatively correlated with Edmondson grade. There were significant differences in the expression of CXCR4 between interstitial CTCs and mixed CTCs. A total of 99 patients underwent CTCs testing prior to surgery. The tumor-free survival time of HCC patients with interstitial CTCs <1 (13.3 months) was significantly longer than patients with interstitial CTCs ≥1 (5.0 months) pre-operatively.
CTC-positivity was shown to be associated with HCC and can be used as an independent prognostic factor for HCC. High CXCR4 protein expression was more common in mixed CTCs.
本研究旨在确定原发性肝细胞癌（HCC）中循环肿瘤细胞（CTC）及CXC趋化因子受体4（CXCR4）的表达情况及其与预后的关系。
我们采用先进的CanPatrol CTC富集技术从血样中收集CTC进行分离和鉴定。基于分支DNA（bDNA）信号放大技术的RNA原位杂交（RNA-ISH）方法，根据术前血样中99例原发性肝癌患者上皮-间质转化（EMT）标志物来确定CXCR4的表达。确定EMT标志物与HCC之间的关系。
CTC和CXCR4的阳性率分别为89.9%和58.8%。CTC与巴塞罗那临床肝癌（BCLC）分期、肿瘤直径和数量、包膜、微卫星损伤、门静脉血栓形成、甲胎蛋白（AFP）及乙肝DNA呈正相关，与Edmondson分级呈负相关。间质CTC和混合CTC中CXCR4的表达存在显著差异。共有99例患者在手术前进行了CTC检测。术前间质CTC<1的HCC患者无瘤生存时间（13.3个月）显著长于间质CTC≥1的患者（5.0个月）。
CTC阳性与HCC相关，可作为HCC的独立预后因素。高CXCR4蛋白表达在混合CTC中更为常见。
