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


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 CanPatrolTM 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.

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