Bang Heejin, Ha Sang Yun, Hwang Soo Hyun, Park Cheol-Keun
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Cancer Res Treat. 2015 Oct;47(4):844-52. doi: 10.4143/crt.2014.124. Epub 2015 Feb 13.
Paternally expressed gene 10 (PEG10), first identified as an imprinted gene, is paternally expressed and maternally silenced. In hepatocellular carcinoma (HCC), PEG10 has been identified as a potential target gene located within the amplified 7q21 locus. The purpose of this study was to investigate the expression of PEG10 protein in HCC and evaluate its prognostic significance.
PEG10 protein expression was examined by immunohistochemistry in tumor tissues from 218 HCC patients undergoing curative resection. Furthermore, the relationships between PEG10 expression and clinicopathologic features or postoperative survival of HCC patients were evaluated. The median follow-up period was 119.8 months for survivors.
PEG10 expression was observed in 148 of the 218 HCCs (67.9%) and was significantly correlated with younger age, female, higher Edmondson grade, microvascular invasion, intrahepatic metastasis, higher American Joint Committee on Cancer T-stage, and higher α-fetoprotein level. PEG10 expression was an independent predictor of early recurrence (p=0.013), and it showed an unfavorable influence on recurrence-free survival (p < 0.001). A subgroup analysis showed that among patients with α-fetoprotein ≤ 20 ng/mL (80 patients), the PEG10-positive group also showed an unfavorable influence on recurrence-free survival (p=0.002). Moreover, a multivariate survival analysis identified PEG10 as an independent predictor of shorter recurrence-free survival (p=0.005). PEG10 expression showed an unfavorable influence on overall survival (p=0.007) but was not an independent predictor of shorter overall survival (p=0.128).
PEG10 protein could be a potential biomarker predicting early recurrence and recurrence-free survival in HCC patients after curative resection, even in those with normal serum α-fetoprotein levels.
父源表达基因10(PEG10)最初被鉴定为印记基因,呈父源表达且母源沉默。在肝细胞癌(HCC)中,PEG10已被确定为位于扩增的7q21位点内的潜在靶基因。本研究旨在调查PEG10蛋白在HCC中的表达情况,并评估其预后意义。
采用免疫组织化学法检测218例行根治性切除的HCC患者肿瘤组织中PEG10蛋白的表达。此外,评估PEG10表达与HCC患者临床病理特征或术后生存的关系。幸存者的中位随访期为119.8个月。
218例HCC中有148例(67.9%)观察到PEG10表达,且与较年轻年龄、女性、较高的Edmondson分级、微血管侵犯、肝内转移、较高的美国癌症联合委员会T分期以及较高的甲胎蛋白水平显著相关。PEG10表达是早期复发的独立预测因素(p = 0.013),对无复发生存有不利影响(p < 0.001)。亚组分析显示,在甲胎蛋白≤20 ng/mL的患者(80例)中,PEG10阳性组对无复发生存也有不利影响(p = 0.002)。此外,多因素生存分析确定PEG10是无复发生存期较短的独立预测因素(p = 0.005)。PEG10表达对总生存有不利影响(p = 0.007),但不是总生存期较短的独立预测因素(p = 0.128)。
PEG10蛋白可能是预测HCC患者根治性切除术后早期复发和无复发生存的潜在生物标志物,即使是血清甲胎蛋白水平正常的患者。