ATAD2 as a Poor Prognostic Marker for Hepatocellular Carcinoma after Curative Resection

PURPOSE: Cancer cells frequently express genes that are specifically or preferentially expressed in male germ cells under normal conditions. The ATPase family AAA domain-containing 2 (ATAD2) is one such and works as an important cofactor for MYC-dependent transcription. In hepatocellular carcinoma (HCC), ATAD2 has been identified as a candidate driver gene located within the amplified 8q24 locus. However, the prognostic significance of ATAD2 protein expression in HCC remains uncertain. MATERIALS AND METHODS: We investigated ATAD2 protein expression by immunohistochemistry in tumor tissue from 182 HCC patients who underwent curative resection. Associations of ATAD2 expression with clinicopathologic variables or prognosis of HCC patients were analyzed. RESULTS: ATAD2 expression was observed in 119 (65.4%) of the 182 HCCs and tended to be independent predictor of early recurrence (p=0.059). ATAD2 expression showed an unfavorable influence on recurrence-free survival (RFS) (p < 0.001). Subgroup analysis among patients with tumor size ≤ 5.0 cm (n=109), patients at Barcelona Clinic Liver Cancer stage 0 or A (n=92), and patients with α-fetoprotein ≤ 20 ng/mL (n=61), the ATAD2-positive groups unfavorably influenced RFS (p=0.008, p=0.009, and p=0.013, respectively). In addition, ATAD2 expression was an independent predictor of shorter RFS (p=0.002). ATAD2 expression showed an unfavorable influence on disease-specific survival (p=0.001), but was not an independent predictor of shorter disease-specific survival (p=0.109). CONCLUSION: ATAD2 protein expression may be a potential predictor of RFS in HCC patients after curative resection and ATAD2 may have prognostic value in patients with early stage HCC or normal serum α-fetoprotein level.