Overexpression of the Chemokine Receptor CCR7 in Patients with Hepatocellular Carcinoma: Correlation with Disseminated Circulating Tumor Cells

Disseminated circulating tumor cells (CTCs) are cancer cells that have detached from the primary tumor and survived in the circulation, thus enable the spread of cancer from its site of origin. The chemokine receptor 7 (CCR7) has been linked to tumor dissemination and poor prognosis in solid tumors. However, its relationships with CTCs in liver cancer still not clear. This study aimed to identify the relationship between CCR7 and CTCs in hepatocellular carcinoma (HCC) patients, and to assess their predictive values as noninvasive markers. Seventy-one HCC patients and 20 normal individuals were included. CTCs were detected in the peripheral blood by flow cytometry defined as CD45¯CK19⁺CD90⁺cells. Expression of CCR7 was assessed by real time PCR. Clinical and routine laboratory investigations included tumor size and number of tumors detected by ultrasound. Also, alpha fetoprotein )AFP), CBC, PT, INR, ALT, AST, bilirubin, albumin, and creatinine were analyzed. Results indicated that HCC patients were classified according to their Childs-Pugh score system (CPSS) into 2 subgroups A5 (N=51) and A6 (n=20). It was found that CCR7^mRNA increased significantly in HCC patients and its elevation was correlated with CTCs count. Besides, there were significant differences in CCR7^mRNA and in CTCs between the studied groups. Both CCR7 and CTCs were significantly correlated with age, levels of ALT, and AST and negatively with platelets and serum albumin. CCR7 ^mRNA was correlated significantly with total bilirubin and tumor size, while CTCs was significantly correlated with AFP and INR. No significant difference between both groups regarding kidney function tests. The diagnostic efficiency of CTCs and CCR7 was assessed using ROC curve, where it was clear that CCR7 at cut off >1.02 could discriminate between patients and control with 93.1% sensitivity, 78.8% specificity, 88.5% PPV and 86.7% NPV, while CTCs concentration> 3.5 is the cutoff between patient and control groups with 91.4% sensitivity, 81.8% specificity, 89.8% PPV and 84.4 % NPV. The current results indicated that each of CCR7 and CTCs can be used as an efficient diagnostic marker, and both complement in reflecting different liver reserve status. Conclusion: CCR7 expression is increased with HCC progression. The combined assessment of CTCs and CCR7 could be considered as potential noninvasive biomarkers for HCC progression. Additional research with a greater number of patients is needed on this topic.