AIM:To investigate the role of glycylproline dipeptidylaminopeptidase(GPDA)isoenzyme in the diagnosis ofprimary hepatocellular carcinoma(PHC),especially in patientswith negative alpha-fetoprotein(AFP).METHODS:A stage gradient polyacrylamide geldiscontinuous electrophoresis system was developed toseparate serum GPDA isoenzymes,which were determinedin 102 patients with PHC,45 cases with liver cirrhosis,24cases with chronic hepatitis,35 cases with benign liver space-occupying lesions,20 cases with metastatic liver cancer and50 cases with extra-hepatic cancer,as well as 80 healthysubjects.The relationships between GPDA isoenzymes andAFP,the sizes of tumors,as well as alanine aminotransferase(ALT)were also analyzed.RESULTS:Serum GPDA was separated into two isoenzymes,GPDA-S and GPDA-F.The former was positive in all subjects,while the latter was found mainly in majority of PHC(85.3 %)and a few cases with liver cirrhosis(11.1%),chronic hepatitis(33.3 %),metastatic liver cancer(15.0 %)and non-hepaticcancer(16.0 %).GPDA-F was negative in all healthy subjectsand patients with benign liver space-occupying lesions,including abscess,cysts and angioma.There was nocorrelation between GPDA-F and AFP concentration or tumorsize.GPDA-F was consistently positive and not correlatedwith ALT in PHC,but GPDA-F often converted to negative asdecline of ALT in benign liver diseases.The electrophoreticmigration of GPDA-F became sluggish after the treatmentof neuraminidase.CONCLUSION:GPDA-F is a new useful serum marker forPHC.Measurement of serum GPDA-F is helpful in diagnosisof PHC,especially in patients with negative AFP.GPDA-F isone kind of glycoproteins rich in sialic acid. AIM: To investigate the role of glycylproline dipeptidylaminopeptidase (GPDA) isoenzyme in the diagnosis of primary hepatocellular carcinoma (PHC), especially in patients with negative alpha-fetoprotein (AFP) .METHODS: A stage gradient polyacrylamide geldiscontinuous electrophoresis system was developed toseparate serum GPDA isoenzymes, which were determined in 102 patients with PHC, 45 cases with liver cirrhosis, 24 cases with chronic hepatitis, 35 cases with benign liver space-occupying lesions, 20 cases with metastatic liver cancer and 50 cases with extra-hepatic cancer, as well as 80 health diseases. relationships between GPDA isoenzymes and AFP, the sizes of tumors, as well as alanine aminotransferase (ALT) were also analyzed .RESULTS: Serum GPDA was separated into two isoenzymes, GPDA-S and GPDA-F.The former was positive in all subjects, while The latter was found mainly in majority of PHC (85.3%) and a few cases with liver cirrhosis (11.1%), chronic hepatitis (33.3%), metastatic liver cancer hepaticcancer (16.0%). GPDA-F was negative in all healthy subjects and patients with benign liver space-occupying lesions, including abscess, cysts and angioma. Having was nocorrelation between GPDA-F and AFP concentration or tumorsize. GPDA-F was consistently positive and not correlatedwith ALT in PHC, but GPDA-F often converted to negative asdecline of ALT in benign liver diseases.The electrophoretic migration of GPDA-F became sluggish after the treatment of neuraminidase. CONCLUSION: GPDA-F is a new useful serum marker for PHC. Measurement of serum GPDA-F is helpful in diagnosis of PHC, especially in patients with negative AFP. GPDA-F is of kind of glycoproteins rich in sialic acid.