Hwang Hye Won, Ha Sang Yun, Bang Heejin, Park Cheol-Keun
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Cancer Res Treat. 2015 Oct;47(4):853-61. doi: 10.4143/crt.2014.177. Epub 2015 Feb 16.
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.
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.
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).
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.
癌细胞常常表达在正常情况下于雄性生殖细胞中特异性或优先表达的基因。含ATP酶家族AAA结构域2(ATAD2)就是其中之一,它作为MYC依赖转录的重要辅助因子发挥作用。在肝细胞癌(HCC)中,ATAD2已被确定为位于扩增的8q24基因座内的候选驱动基因。然而,ATAD2蛋白表达在HCC中的预后意义仍不明确。
我们通过免疫组织化学研究了182例行根治性切除的HCC患者肿瘤组织中的ATAD2蛋白表达情况。分析了ATAD2表达与HCC患者临床病理变量或预后的相关性。
182例HCC中有119例(65.4%)观察到ATAD2表达,且倾向于成为早期复发的独立预测因子(p = 0.059)。ATAD2表达对无复发生存期(RFS)有不利影响(p < 0.001)。在肿瘤大小≤5.0 cm的患者(n = 109)、巴塞罗那临床肝癌分期0或A期的患者(n = 92)以及甲胎蛋白≤20 ng/mL的患者(n = 61)的亚组分析中,ATAD2阳性组对RFS有不利影响(分别为p = 0.008、p = 0.009和p = 0.013)。此外,ATAD2表达是RFS较短的独立预测因子(p = 0.002)。ATAD2表达对疾病特异性生存有不利影响(p = 0.001),但不是疾病特异性生存较短的独立预测因子(p = 0.109)。
ATAD2蛋白表达可能是HCC患者根治性切除后RFS的潜在预测因子,且ATAD2可能对早期HCC或血清甲胎蛋白水平正常的患者具有预后价值。