| Objective:Circulating tumor cells(CTCs)are the "seeds" of tumor metastasis,and their clinical application values such as prognosis prediction and efficacy evaluation in various solid malignant tumors have been widely confirmed.In recent years,more and more studies have found that CTC may be involved in the regulation of the tumor immune microenvironment and the early formation of micro-metastases by aggregating with immune cells(such as white blood cells)in the blood circulation.The study showed that tumor patients with CTC-WBC cell clusters detected in peripheral blood before surgery had a significantly shorter time to recurrence.However,the clinical value of CTC-WBC cell clusters for predicting metastasis in hepatocellular carcinoma(HCC)patients remains unclear.The purpose of this study was to investigate the correlation between CTC-WBC cell clusters and the clinicopathological characteristics of HCC patients,and to observe the difference in Metastasis free survival(MFS)between patients with detected CTC-WBC cell clusters and those with undetected HCC.To explore the possibility of CTC-WBC cell clusters as a new biomarker for predicting early recurrence of liver cancer,combined with conventional imaging detection methods,to provide new clinical ideas for the development of more sensitive and accurate tumor metastasis diagnosis and monitoring methods.Methods and Materials:This study retrospectively analyzed 136 patients with hepatocellular carcinoma who were treated in NanFang Hospital of Southern Medical University from October 2014 to March 2020.Use CanPatrol? noval CTC typing detection technology to separate and enrich CTCs and CTC-WBC cell clusters in peripheral blood of patients;combined with multiple RNA probe in situ hybridization method,realize the epithelial-mesenchymal transition(Epithelial to Mesenchymal Transition,EMT)of CTC type.Chi-square test was used to calculate and analyze the correlation between CTC-WBC cell map and clinicopathological characteristics of liver cancer patients,and Kaplan-Meier survival curve and Cox regression analysis were used to evaluate the prognosis of patients.Results:The positive rate of CTC detection in 136 HCC patients was 93.4%(127/136),with a median of 9/5 mL(range:0-118/5 mL).The positive rates of E-CTC and EMT-CTC were 66.1%(84/127)and 82.3%(112/127),respectively;the range and median number were 2/5 mL(range:1-46/5 mL).)and 8/5 mL(range:1-84/5 mL).The detection rate of CTC-WBC cell clusters was 31.6%(43/127),with a median of 1 cell/5 mL(range:1-4 cells/5 mL).CTC-WBC clusters were associated with TNM staging(P=0.036),portal vein tumor thrombus(P=0.022)and extrahepatic metastasis(P=0.001).No correlation was found between the number of total CTCs,the number of EMT-CTCs and the clinicopathological features of liver cancer.There was a correlation(all P values were greater than 0.05).Among liver cancer patients with CTC detection before treatment,the recurrence-free survival of patients with CTC-WBC clusters detected was significantly shorter than that of patients without detection(P=0.014).Twenty-two patients underwent multiple CTC tests,and 11 of them had tumor recurrence confirmed by imaging during follow-up.Longitudinal analysis of CTC detection results showed that the number of CTC-WBC clusters in the recurrence group was significantly higher than that in the non-relapse group(P=0.005).Imaging examinations showed a trend of tumor recurrence at 10 months.Conclusion:GTC-WBC cell clusters are significantly associated with poor prognosis of liver cancer patients,and it is expected to become a new biomarker for accurate prognosis of liver cancer.Dynamic monitoring of the changes of total CTC,EMT-CTC,especially CTC-WBC clusters before treatment,after treatment and during re-examination is helpful for early indication of tumor recurrence and metastasis. |
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