Impact Of PRFA On CTCs In Peripheral Vein And Clinical Implication Of CTCs Phenotype In Portal Vein Of CLM

Background and purposeLiver malignant tumors include primary liver cancer and secondary liver cancer(metastatic liver cancer).Primary liver cancer is one of the highest death rates of cancer in the world.Especially in China,the annual incidence of primary liver cancer accounts for about half of the global annual incidence.Moreover,the hepatic blood flow is abundant because of the hepatic artery and portal vein double blood supply.Due to the characteristics of blood supply and local special microenvironment,the liver is the most common metastatic site of malignant tumor.Percutaneous radiofrequency ablation(PRFA)converts radiofrequency waves into heat energy,which leads to target tissue dehydration and eventually results in the coagulative necrosis of target cells.This efficacious technique has been used for more than 20 years,and PRFA has become an increasingly common therapeutic technique for patients with hepatocellular carcinoma or metastatic liver cancer.Circulating tumor cells(CTCs)is the main subject of our study.CTCs are tumor cells in the circulatory system that originate from solid tumor lesions,and they possess the potential to develop into metastases.Cancer cells enter the circulatory system as a result of diagnostic or therapeutic surgery or spontaneous tumor shedding.CTCs are closely related to hematogenous metastasis of colorectal cancer(CRC),representing the poor prognosis of patients with colorectal cancer.Up till the present moment,reports on the effect of PRFA on CTCs are limited.Compared with surgery,PRFA had been reported to increase the number of CTCs in peripheral circulation.Nevertheless,such reports included only a small number of patients with hepatocellular carcinoma and/or colorectal liver metastases,and they did not explore changes in the phenotypes of CTC and other related factors.Moreover,the diameter of capillaries ranges from 5 to 10 ?m,while the diameter of tumor cells can reach 20 ?m.Logically,because of the mechanical filtration of capillary network or microcirculation,CTCs may be arrested in capillaries.Exploring the difference between the number and phenotype of CTCs in portal vein and peripheral vein can help us gain a more comprehensive and profound understanding of the CTCs-filtration-function of capillary network and the clinical significance of different phenotypes of CTCs in portal vein.Therefore,our research consists of two parts:The first part aims to further explore the impact of PRFA on number and phenotypes of CTCs in patients with hepatocellular carcinoma or metastatic liver cancer.The second part aims to investigate the clinical implication of different phenotypes of CTCs in portal vein of patients with colorectal liver metastases(CLM).MethodsIn the first part research,a total of 43 patients with hepatocellular carcinoma or 7 types of metastatic liver tumors were treated with PRFA.We collected blood samples from the peripheral vein 30 min before and 3 days after PRFA.Besides,we also collected blood cell analysis and liver function indexes of all patients,as well as immune cell subsets and tumor markers in some patients at the same two time points.Then combined with the general situation,the tumor background,the PRFA operating factors and the history of treatment,comprehensive statistical analyses were made.As for the second par't research,21 patients with CLM were enrolled in this study.Peripheral venous(PeV)and portal vein(PoV)blood specimens were collected from each patient,and comprehensive statistical analyses were conducted combined with individual clinical data of each patient.ResultsBased on a comprehensive statistical analysis of multiple clinical data,patient background and CTCs quantity and phenotype,we obtained the following main results for the first research purpose:(?)Total CTC level increased after PRFA,particularly the mesenchymal phenotype CTCs.(?)The number of ablation points showed a partial correlation with the changes in the number of CTCs.(?)Lymphocytes decreased significantly after PRFA,and CTCs increased significantly in patients with reduced lymphocytes.We found following results after studying the second purpose:(?)No difference was found in the number of CTCs between PoV and PeV,but the number of epithelial CTCs from PoV is higher than that from PeV.(?)Epithelial CTCs in PoV associate with the number of liver metastatic nodules.(?)The proportion of epithelial CTCs in PoV is higher in CLM patients with increased level of serum CEA and low lymphocytes.Conclusion1.Total CTCs level increased after PRFA,particularly the mesenchymal phenotype CTCs.2.The number of ablation points showed a partial correlation with the changes in the number of CTC.3.Lymphocytes decreased significantly after PRFA,and CTCs increased significantly in patients with reduced lymphocytes.4.No difference was found in the number of CTCs between PoV and PeV,but the number of epithelial CTCs from PoV is higher than that from PeV.5.Epithelial CTCs in the PoV relates to a more aggressive CLM.