Circulating tumor cells and CXCR4 in the prognosis of hepatocellular carcinoma

Tao Bai; Rongyun Mai; Jiazhou Ye; Jie Chen; Lunan Qi; Juan Tang; Meng Wei; Lianda Zhang; Zhiwei Chen; Zhihong Tang; Lequn Li; Feixiang Wu

doi:10.21037/tcr.2020.01.14

Circulating tumor cells and CXCR4 in the prognosis of hepatocellular carcinoma

Transl Cancer Res. 2020 Mar;9(3):1384-1394. doi: 10.21037/tcr.2020.01.14.

Authors

Tao Bai^#^{1

2

3}, Rongyun Mai^#^{1

2

3}, Jiazhou Ye^#^{1

2

3}, Jie Chen^#^{1

2

3}, Lunan Qi^{1

2

3}, Juan Tang^{1

2

3}, Meng Wei^{1

2

3}, Lianda Zhang^{1

2

3}, Zhiwei Chen^{1

2

3}, Zhihong Tang^{1

2

3}, Lequn Li^{1

2

3}, Feixiang Wu^{1

2

3}

Affiliations

¹ Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 530021, China.
² Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning 530021, China.
³ Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Nanning 530021, China.

^# Contributed equally.

Abstract

Background: 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.

Methods: We used an advanced CanPatrol^TM 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.

Results: 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.

Conclusions: 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.

Keywords: Hepatocellular carcinoma (HCC); chemokine receptor; circulating tumor cells (CTCs); prognosis.