Objective To investigate the value of combined measurement of alpha-fetoprotein (AFP) , carbohydrate antigen 19-9 (CA19-9) , and carcinoembryonic antigen (CEA) in the early diagnosis of primary liver cancer.Methods A total of 248 patients who visited the outpatient service or were hospitalized in The Second Hospital of Nanjing from October 2014 to December 2016 were enrolled and divided into primary liver cancer group with 88 patients and non-tumor liver disease group with 160 patients.A total of 130 healthy subjects who underwent physical examination were enrolled as normal control group.The Roche cobas e 411 analyzer was used to measure the serum levels of the tumor markers AFP, CA19-9, and CEA, and the sensitivities and specificities of these markers or a combination of them were analyzed.Beckman Coulter AU5800 was used to measure biochemical parameters for liver function, and Biotek ELX808 was used to measure hepatitis B virus markers and HCV antibody.The receiver operating characteristic (ROC) curve was used to analyze the results of measurements of serum AFP, CA19-9, and CEA alone or in combination in patients with primary liver cancer.A one-way analysis of variance was used for comparison of continuous data between multiple groups and the SNK-q test was used for further comparison between two groups;the t-test was used for comparison of continuous data between two groups.The chi-square test was used for comparison of categorical data between groups.The Spearman correlation analysis was also performed.Results In the primary liver cancer group and the non-tumor liver disease group, the patients with abnormal liver function had significantly higher levels of AFP and CA19-9 than those with normal liver function (primary liver cancer group:t=35.64 and 3.38, both P<0.05;non-tumor liver disease group:t=12.51 and 8.19, both P<0.05) .Among the patients with normal liver function, the primary liver cancer group had a significantly higher level of CEA than the non-tumor liver disease group and the normal control group (all P<0.05) .Among the patients with abnormal liver function, the primary liver cancer group had significantly higher levels of AFP, CA19-9, and CEA than the non-tumor liver disease group and the normal control group (all P<0.05) .The serum levels of AFP, CA19-9, and CEA increased with the increase in Child-Pugh class.Among the patients with abnormal liver function in the primary liver cancer group, Child-Pugh class B patients had significant increases in the levels of AFP, CA19-9, and CEA compared with Child-Pugh class A patients, and Child-Pugh class C patients had significant increases compared with Child-Pugh class B patients (all P<0.05) .Among the patients with abnormal liver function in the non-tumor liver disease group, Child-Pugh class B patients had significant increases in the levels of AFP and CA19-9 compared with Child-Pugh class A patients, and Child-Pugh class C patients had significant increases compared with Child-Pugh class B patients (all P<0.05) ;Child-Pugh class C patients had a significant increase in the level of CEA than Child-Pugh class A/B patients (P<0.05) .The primary liver cancer group had significantly higher positive rates of AFP, CA19-9, and CEA than the non-tumor liver disease group and the normal control group (all P<0.05) , and the positive rates of these tumor markers were significantly higher when measured in combination than when measured alone (all P<0.05) .In the primary liver cancer group, a combination of the three tumor markers had a sensitivity of 86.36% and a specificity of 92.35%, while AFP, CA19-9, and CEA measured alone had sensitivities of 71.59%, 52.27%, and 39.77%, respectively.In the patients with primary liver cancer, the areas under the ROC curve for serum AFP, CA19-9, CEA, and a combination of them were 0.776, 0.704, 0.681, and0.817, respectively.AFP was positively correlated with gamma-glutamyl transpeptidase in the primary liver cancer group (r=0.54, P=0.04) and was positively correlated with indirect bilirubin (IBil) in the normal control group (r=0.50, P=0.01) .In the primary liver cancer group, CA19-9 was positively correlated with alanine aminotransferase (ALT) , direct bilirubin (DBil) , IBil, total bilirubin (TBil) , and total bile acid (TBA) (r=0.58, 0.63, 0.61, 0.65, and 0.58, all P<0.05) , and in the non-tumor liver disease group, CA19-9 was positively correlated with ALT, alkaline phosphatase (ALP) , DBil, IBil, TBil, and TBA (r=0.51, 0.63, 0.66, 0.64, 0.70, and 0.59, all P<0.05) .Conclusion AFP can well reflect liver injury, but it may yield false-negative results in the diagnosis of primary liver cancer.A mild increase in CEA does not strongly indicate primary cancer.CA19-9 is easily influenced by the factors including ALP and bilirubin and has a high false-positive rate.Combined measurement of AFP, CA19-9, and CEA can improve the sensitivity of the diagnosis of primary liver cancer and is better than single measurement of AFP, CA19-9, or CEA.Therefore, it provides a strong basis for early diagnosis and treatment.
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