To investigate the molecular markers of DNA copy number aberrations (CNAs) for extrahepatic metastasis in postoperative hepatocellular carcinoma (HCC).

The genomic CNA of 66 HCC samples was detected by high-resolution Agilent 244K array comparative genomic hybridization. The correlation between CNAs and extrahepatic metastasis in postoperative HCC was analyzed using univariate and multiple stepwise Cox regression models.

Univariate analysis showed that gains at 6p21.32, 15q11.2 and 20q12-13.13, and losses at 4q12 and 4q28.1-35.2, together with a history of hypertension, complete tumor capsule, TNM stage, platelet count and prothrombin time, were associated with increased risk of extrahepatic metastasis (all P<0.05). Multiple stepwise Cox regression analyses revealed that 6p21.32 gain (HR=3.65, 95% CI=1.38~9.62) and 4q28.1-35.2 loss (HR=0.24, 95% CI=0.09~0.65), together with a history of hypertension and TNM stage, were independent prognostic markers of extrahepatic metastasis. Survival analysis showed that non-metastatic survival among the 3 groups of HCCs with 6p21.32 gain, with 4q28.1-35.2 loss but without 6p21.32 gain, and without 6p21.32 gain and with 4q28.1-35.2 loss were significantly different (log-rank test, P<0.05).

Both 6p21.32 gain and 4q28.1-35.2 loss in HCC were two independent prognostic markers of postoperative extrahepatic metastasis. These findings may help to identify patients who are at risk of extrahepatic metastasis after surgery.

Hepatocellular carcinoma; Extrahepatic metastasis; Array comparative genomic hybridization; Copy number aberration