Li Bing, Shao Qing, Ji Dong, Li Fan, Guo Xiaodong, Chen Guofeng
Diagn Pathol. 2014 Oct 23;9:209. doi: 10.1186/s13000-014-0209-5.
N-Myc downstream-regulated gene 2 (NDRG2), as a tumor suppressor, has been demonstrated to inhibit tumor invasion and migration of hepatocellular carcinoma (HCC) by reducing the expression of CD24, which has been identified as a prognostic factor for HCC patients. However, the clinical significance of combined NDRG2 and CD24 expression in HCC remains unclear. Thus, the aim of the current study was to investigate the relationship of NDRG2 and CD24 expression with clinicopathological parameters and patients' survival.
Immunohistochemistry was performed to detect the expression and subcellular localizations of NDRG2 and CD24 proteins in 130 pairs of HCC and adjacent nonneoplastic liver tissues.
NDRG2 protein was strongly expressed in the cytoplasm and plasma membrane of hepatocytes in adjacent nonneoplastic liver tissues, whereas its immunostaining was weak or negative in HCC tissues. In contrast, CD24 protein exhibited the cytoplasm immunostaining in tumor cells of HCC tissues but showed negative expression in adjacent nonneoplastic liver tissues. The statistical analysis also showed that the expression levels of NDRG2 and CD24 proteins in HCC tissues were respectively lower and higher than those in adjacent nonneoplastic liver tissues significantly (both P<0.001). In addition, there was an inverse correlation between NDRG2 expression and CD24 expression in HCC tissues (P=0.02). Moreover, combined NDRG2 downregulation and CD24 upregulation (NDRG2-low/CD24-high) more frequently occurred in HCC tissues with high serum AFP (P=0.03), advanced tumor stage (P=0.001) and high tumor grade (P=0.02). Furthermore, HCC patients with NDRG2-low/CD24-high expression showed shortest 5-year disease-free survival and 5-year overall survival (both P<0.001) of four groups (NDRG2-low/CD24-high, NDRG2-low/CD24-low, NDRG2-high/CD24-high, NDRG2-high/CD24-low). Of note, the multivariate survival analysis showed that the combined aberrant expression of NDRG2 and CD24 proteins was an independent prognostic factor for both 5-year disease-free survival and 5-year overall survival (both P=0.01) in HCC.
These findings suggest that the downregulation of NDRG2 combined with the upregulation of CD24 may play a synergistic role in the occurrence and progression of HCC. A combined detection of NDRG2/CD24 expression may benefit us in determining the prognosis in patients with HCC.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_209.
N-Myc下游调控基因2（NDRG2）作为一种肿瘤抑制因子，已被证明可通过降低CD24的表达来抑制肝细胞癌（HCC）的肿瘤侵袭和迁移，而CD24已被确定为HCC患者的一个预后因素。然而，NDRG2和CD24联合表达在HCC中的临床意义仍不清楚。因此，本研究的目的是探讨NDRG2和CD24表达与临床病理参数及患者生存的关系。
采用免疫组织化学法检测130对HCC及癌旁非肿瘤肝组织中NDRG2和CD24蛋白的表达及亚细胞定位。
NDRG2蛋白在癌旁非肿瘤肝组织的肝细胞胞质和质膜中强表达，而在HCC组织中其免疫染色较弱或为阴性。相反，CD24蛋白在HCC组织的肿瘤细胞中呈胞质免疫染色，但在癌旁非肿瘤肝组织中呈阴性表达。统计学分析还显示，HCC组织中NDRG2和CD24蛋白的表达水平分别显著低于和高于癌旁非肿瘤肝组织（均P<0.001）。此外，HCC组织中NDRG2表达与CD24表达呈负相关（P=0.02）。而且，NDRG2下调与CD24上调联合（NDRG2低/CD24高）在血清AFP水平高（P=0.03）、肿瘤分期晚（P=0.001）和肿瘤分级高（P=0.02）的HCC组织中更常见。此外，NDRG2低/CD24高表达的HCC患者在四组（NDRG2低/CD24高、NDRG2低/CD24低、NDRG2高/CD24高、NDRG2高/CD24低）中5年无病生存率和5年总生存率最短（均P<0.001）。值得注意的是，多因素生存分析显示，NDRG2和CD24蛋白的联合异常表达是HCC患者5年无病生存率和5年总生存率的独立预后因素（均P=0.01）。
这些发现表明，NDRG2下调与CD24上调可能在HCC的发生和发展中起协同作用。联合检测NDRG2/CD24表达可能有助于我们判断HCC患者的预后。
本文的虚拟切片可在此处找到：http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_209 。
