Study On The Prognostic Value Of AFP,CEA And Ki67 In Intrahepatic Cholangiocarcinoma

Background:Intrahepatic cholangiocarcinoma is the second most common primary malignant tumor of the liver after hepatocellular carcinoma.Due to the complex anatomical structure of the disease and the lack of specific tumor markers,the disease was in the middle and advanced stage at the time of diagnosis.That is to say,early diagnosis of this disease is difficult.In the process of disease progression,tumors are prone to invasive growth and jumping metastasis,which often leads to poor prognosis.At present,surgical resection is still the first choice for the treatment of ICC,but the factors affecting the postoperative prognosis of patients are not completely clear.Nowadays,with the continuous development of clinical diagnosis and treatment technology and the research and development of new immune targeted drugs,the survival time of ICC patients has been improved to a certain extent,but its long-term survival rate is still not as expected.Therefore,it is still very important to explore the factors that affect the prognosis of ICC.Objective:The aim of this study was to investigate the correlation between the expression levels of AFP,CEA and Ki67 in ICC tumor tissues and the clinicopathological characteristics.In addition,their roles in assessing the prognosis of ICC were also analyzed.Methods:This study retrospectively analyzed patients who underwent radical surgical resection in the Department of Hepatobiliary Surgery of Henan Provincial People’s Hospital from January 2012 to January2019 and were diagnosed with intrahepatic cholangiocarcinoma by postoperative pathology.The complete clinical data and postoperative survival data of patients were collected by a combination of outpatient,inpatient,medical record review and telephone follow-up.The expression levels of AFP,CEA and Ki67 in tumor tissues were evaluated by immunohistochemistry,and their correlation with clinicopathological features was analyzed.Kaplan Meier method was used to calculate the overall survival rate of patients and draw the survival curve.Univariate and Cox multivariate statistical analysis were used to identify independent risk factors for disease-free survival(DFS)and overall survival(OS)in patients.Results:1、According to the results of immunohistochemistry,among the 103 patients,45(43.7%)cases were in the high AFP expression group,58(56.3%)cases were in the low AFP expression group;47(45.6%)cases were in the CEA high expression group,and 56(54.4%)cases were in the CEA low expression group;57 cases(55.3%)were in the high Ki67 expression group and 46 cases(44.7%)were in the low Ki67 expression group.2、There were significant differences in ALB,tumor differentiation,tumor diameter and tumor number between the AFP high-expression group and the low-expression group(P<0.05).There was a statistically significant difference between the CEA high expression group and the low expression group in terms of diabetes history indicators(P<0.05),and the expression level of Ki67 was associated with CA12-5,ALT,lymph node metastasis,and vascular invasion(P<0.05).3、Univariate analysis indicated that ICC patients with higher AFP(P<0.001),CEA(P<0.017),Ki67(P=0.001),CA19-9(P=0.032),CA12-5(P=0.037),tumor diameter ≥5cm(P=0.023),multiple tumors(P=0.016),lymph node metastasis(P=0.006),vascular invasion(P=0.048),not receiving adjuvant treatment(P=0.024),and TNM III+IV staging(P<0.001)had worse OS.Meanwhile,higher AFP(P<0.001),CEA(P=0.012),Ki67(P=0.002),CA19-9(P=0.018),CA12-5(P=0.014),tumor diameter ≥5cm(P=0.013),multiple tumors(P=0.008),lymph node metastasis(P=0.023),not receiving adjuvant treatment(P=0.008),and TNM III+IV staging(P<0.001)were associated with worse DFS.4 、 Cox multivariate analysis showed that the high expression of AFP(HR=2.004,95%CI:1.146-3.504 P=0.015),CEA(HR=2.226,95%CI:1.283-3.861 P=0.004),Ki67(HR=3.785,95%CI:2.073-6.909 P<0.001)and TNM III+IV staging(HR=2.900,95%CI:1.498-5.757 P=0.002)were independent risk factors affecting the overall survival of ICC patients.Furthermore,higher AFP(HR=2.172,95%Cl: 1.291-3.654 P=0.003),CEA(HR=1.934,95%Cl: 1.180-3.169 P=0.009),Ki67(HR= 2.203,95%Cl:1.291-3.761 P=0.004)and TNM III+IV staging(HR=1.678,95%Cl:1.025-2.749 P=0.040)were independent risk factors affecting the DFS of ICC patients.5、The results of Kaplan-Meier survival curve survival analysis showed that the 1-year and 3-year survival rates of ICC patients in the high expression group of AFP,CEA and Ki67 were significantly lower than those in the low expression group(P<0.05).The two and three combination indexes based on AFP,CEA and Ki67 were independent risk factors for the prognosis of ICC.The prediction performance of combined index was higher than that of single index.The area under ROC curve of “AFP+CEA+Ki67” was the largest(AUC=0.724,95% CI: 0.681-0.764),which has the highest monitoring efficiency.Conclusion:1、The expression levels of AFP,CEA and Ki67 in tumor tissues are related to the prognosis of ICC.The 1-year and 3-year survival rates of patients in the high expression group are significantly lower than those in the low expression group.2、The high expression of AFP,CEA and Ki67 are independent risk factors for prognosis of ICC patients after hepatectomy.The combination of AFP,CEA and Ki67 could significantly improve the prognosis of ICC.And they could represent a valuable addition to the existing prognostic factors to find an ideal and individual therapeutic approach for ICC patients.