Objective: This study aimed to evaluate the relationships between members of APOBEC3 in tumor tissues and hepatocellular carcinoma (HCC) aggressiveness and prognosis. Methods: Using the expression profile GSE36376 from Gene Expression Omnibus (GEO), we compared APOBEC3 expression between tumor and non-tumor tissues, and correlated this with clinico-pathological features and outcomes of HCC patients. Results: A3B, A3D, A3F and A3H were overexpressed in HCC tumor tissues compared to non-tumor

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... ues (all P≤0.001). Cox regression shown that A3G was negatively associated with overall survival of HCC patients (HR=2.277, 95% CI=1.324-3.915, P=0.033), in contrast, A3C level in tumor tissues might play a positive role in HCC overall survival (HR=0.364, 95% CI=0.182-0.727, P=0.004). Interestingly, A3F contributed to a poor disease-free survival of HCC (HR=3.383, 95% CI=1.249-9.715, P=0.017), while A3H may be a positive factor associated with HCC disease-free survival (HR=0.25, 95% CI=0.098-0.636, P=0.004). Cirrhosis, tumor size and intrahepatic metastasis were associated with HCC poor disease-free survival (HR=1.838, 95% CI=1.308-2.583, P<0.001; HR= 1.095, 95% CI=1.042-1.15, P<0.001 and HR=3.669, 95% CI=2.447-5.5, P<0.001; respectively). Logistic regression analysis indicated that up-regulation of A3F in tumor tissues promoted HCC vascular invasion, intrahepatic metastasis and AFP elevation (all P<0.05). In contrast, A3H might decrease these risks (all P<0.05). Conclusions: APOBEC3G and APOBEC3F might be risk factors for HCC development and survival, while APOBEC3C and APOBEC3H should play positive roles in HCC aggressiveness and prognosis. Further investigation for APOBEC3 mechanisms are needed in the future.