Abstract
Background
IL34 involves in host immunity regulated carcinogenesis. Alpha-fetoprotein (AFP) is related to the development of HCC. We explored if combination of IL-34 and APF could improve the diagnostic value in HBV related hepatocellular carcinoma (HBVHCC).
Methods
Serum was obtained from HBV patients or healthy control. Liver tissue was obtained from liver biopsy in CHB, HBV related cirrhosis patients or curative resection in HBVHCC patients. Serum IL34 and MCSF were measured. Hepatic IL34, MCSF and CD68+ tumor associate macrophages (TAMs) were determined.
Results
Serum IL34 was 1.7, 1.3 or 2.3-fold higher in HBVHCC than that of CHB, HBV related cirrhosis, or healthy control, which was inhibited following transhepatic arterial chemoembolization (TACE) in HBVHCC patients. Intrahepatic IL34 was higher in HBVHCC than that of the other three groups. Intra-hepatic IL34 was associated with high HBVDNA, HBeAg−, poor differentiation and small tumor size of HBVHCC patients. Intra-hepatic TAMs in HBVHCC were increased 1.7 or 1.3-fold, compared to that from CHB or HBV-cirrhosis patients. Intra-hepatic TAMs were associated with high HBVDNA, high tumor differentiation, small tumor size, abnormal AFP and more tumor number. AFP plus serum IL-34, showed the highest AUC (0.837) with sensitivity (0.632) and highest specificity (0.931), suggesting that AFP plus IL-34 enhances the reliability for prediction of the development of HBVHCC among CHB patients.
Conclusions
Circulating and intra-hepatic IL34 was upregulated gradually in HBV disease progression from CHB, cirrhosis and HCC. IL-34 may be used as a diagnostic biomarker and potential therapeutic target for the management of HBVHCC.