Study On The Relationship Among Circulating Tumor Cell,immunoinflammatory Indexes And Prognosis For Hepatocellular Carcinoma

Background:Primary liver cancer has developed into one of the most common malignant tumors in the current world,and the incidence and mortality are on the rise.More than half of the patients with liver cancer are here in China,which pose a great burden to medical care.Hepatocellular carcinoma(HCC)accounts for a significant proportion and remains the major type of primary liver cancer.Surgical approaches including hepatectomy and liver transplantation are still the major treatments,but only a small proportion of HCC patients conform to the indications at diagnosis.Even worse,early-stage recurrence and metastasis rate remains high.Therefore,more sensitive,efficient and specific predictors for HCC are urgently needed.Recent studies have shown that circulating tumor cell and preoperative immunoinflammatory index may be independent predictors of prognosis for the disease,but the mechanism has not been fully illuminated.In addition,relationship among circulating tumor cell,immunoinflammatory indexes,and their potential prediction of prognosis for hepatocellular carcinoma are still unclear.Objective:Our study aims to explore the relationship among different types of circulating tumor cell(including multicellular clone CTC,namely MC-CTC and oligocellular clone CTC,namely OC-CTC),preoperative immunoinflammatory indexes and clinical features of hepatocellular carcinoma,and make a preliminary investigation on the significance of circulating tumor cell combined with immunoinflammatory indexes as new biomarkers to predict earlystage metastasis and recurrence and prognosis for patients with hepatocellular carcinoma.Methods:HCC patients who underwent radical surgery and peripheral venous blood drawn for CTC culture and immunoinflammatory indexes detection in Department of Organ Transplantation,Naval Medical University from December 2015 to February 2017 were included for retrospective analysis,and the final follow-up date was January 31,2022.The relationship among circulating tumor cell,clinical features and immunoinflammatory indexes,and their values on prognosis were analyzed respectively.Results:Part 1 Analysis of circulating tumor cell and immunoinflammatory indexes on the long-term prognosis for patients with hepatocellular carcinomaChild-Pugh score(HR = 3.939,95% CI: 1.241-12.502,P = 0.020),satellite nodule(HR = 3.929,95% CI: 1.200-12.868,P = 0.024)and CTC count(HR = 1.013,95% CI:1.004-1.022,P = 0.003)were independent risk factors affecting the long-term survival of patients with HCC.Pathological grade(HR = 3.647,95% CI: 1.367-9.731,P = 0.010),microvascular invasion(HR = 3.879,95% CI: 1.229-12.240,P = 0.021),CTC count(HR= 1.009,95% CI: 1.000-1.017,P = 0.045)and high preoperative ANRI level(HR = 6.555,95% CI: 2.391-17.975,P < 0.001)were independent risk factors for postoperative recurrence of HCC.Part 2 Study on relationship among circulating tumor cell,clinical features and immunoinflammatory indexes in patients with hepatocellular carcinoma1、There was a positive correlation between CTC count and preoperative MLR or SIRI level in HCC patients(P = 0.017;P = 0.024);There was no significant correlation between CTC count and age,gender,cirrhosis,Child-Pugh score,number of tumors,diameter of the largest tumor,serum AFP level,tumor stage,surgery option,pathological grade,microvascular invasion,tumor capsule,satellite nodule and preoperative ALRI,ANRI,APRI,CAR,NLR,PLR,SII.(P > 0.05).2、There was no significant correlation between MC-CTC and age,gender,cirrhosis,Child-Pugh score,number of tumors,diameter of the largest tumor,serum AFP level,tumor stage,surgery option,pathological grade,microvascular invasion,tumor capsule,satellite nodule and immunoinflammatory indexes(P > 0.05).3、OC-CTC count was positively correlated with preoperative MLR and SIRI level in HCC patients(P = 0.009;P = 0.014);There was no significant correlation between OC-CTC count and age,gender,cirrhosis,Child-Pugh score,number of tumors,diameter of the largest tumor,serum AFP level,tumor stage,surgery option,pathological grade,microvascular invasion,tumor capsule,satellite nodule and preoperative ALRI,ANRI,APRI,CAR,NLR,PLR,SII.(P > 0.05).OC-CTC count showed some similarities with CTC count.Part 3 Exploration of relationship between circulating tumor cell and early-stage recurrence in postoperative hepatocellular carcinoma patientsCTC count(HR = 1.012,95% CI: 1.000-1.024,P = 0.048)and tumor capsule invasion(HR = 4.814,95% CI: 1.345-17.232,P = 0.016)were risk factors for early-stage recurrence after radical surgery of HCC.Conclusions:1、Higher CTC count indicated worse long-term survival outcomes of HCC patients after hepatectomy or liver transplantation,and higher risk of postoperative early-stage recurrence.2、High preoperative ANRI level(ANRI > 16.50)might significantly increase the risk of recurrence and metastasis in postoperative HCC patients.3、CTC count was positively correlated with preoperative MLR and SIRI.OC-CTC showed some similarities with CTC count,and there was no remarkable relationship among MC-CTC,clinical features and immunoinflammatory indexes.