ATAD2 as a Poor Prognostic Marker for Hepatocellular Carcinoma after Curative Resection
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Purpose Cancer cells frequently express genes that are specifically or preferentially expressed inmale 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 genelocated within the amplified 8q24 locus. However, the prognostic significance of ATAD2protein expression in HCC remains uncertain. Materials and MethodsWe investigated ATAD2 protein expression by immunohistochemistry in tumor tissue from182 HCC patients who underwent curative resection. Associations of ATAD2 expressionwith clinicopathologic variables or prognosis of HCC patients were analyzed. ResultsATAD2 expression was observed in 119 (65.4%) of the 182 HCCs and tended to be independentpredictor of early recurrence (p=0.059). ATAD2 expression showed an unfavorableinfluence on recurrence-free survival (RFS) (p < 0.001). Subgroup analysis among patientswith tumor size ! 5.0 cm (n=109), patients at Barcelona Clinic Liver Cancer stage 0 or A(n=92), and patients with "-fetoprotein ! 20 ng/mL (n=61), the ATAD2-positive groupsunfavorably 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 expressionshowed an unfavorable influence on disease-specific survival (p=0.001), but was notan independent predictor of shorter disease-specific survival (p=0.109). ConclusionATAD2 protein expression may be a potential predictor of RFS in HCC patients after curativeresection and ATAD2 may have prognostic value in patients with early stage HCC or normalserum "-fetoprotein level.
Abstract
Purpose Cancer cells frequently express genes that are specifically or preferentially expressed inmale 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 genelocated within the amplified 8q24 locus. However, the prognostic significance of ATAD2protein expression in HCC remains uncertain. Materials and MethodsWe investigated ATAD2 protein expression by immunohistochemistry in tumor tissue from182 HCC patients who underwent curative resection. Associations of ATAD2 expressionwith clinicopathologic variables or prognosis of HCC patients were analyzed. ResultsATAD2 expression was observed in 119 (65.4%) of the 182 HCCs and tended to be independentpredictor of early recurrence (p=0.059). ATAD2 expression showed an unfavorableinfluence on recurrence-free survival (RFS) (p < 0.001). Subgroup analysis among patientswith tumor size ! 5.0 cm (n=109), patients at Barcelona Clinic Liver Cancer stage 0 or A(n=92), and patients with "-fetoprotein ! 20 ng/mL (n=61), the ATAD2-positive groupsunfavorably 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 expressionshowed an unfavorable influence on disease-specific survival (p=0.001), but was notan independent predictor of shorter disease-specific survival (p=0.109). ConclusionATAD2 protein expression may be a potential predictor of RFS in HCC patients after curativeresection and ATAD2 may have prognostic value in patients with early stage HCC or normalserum "-fetoprotein level.
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