核孔蛋白 2 在人卵巢恶性生殖细胞肿瘤中的过表达与不良预后相关。
Overexpression of karyopherin 2 in human ovarian malignant germ cell tumor correlates with poor prognosis.
机构信息
State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
出版信息
PLoS One. 2012;7(9):e42992. doi: 10.1371/journal.pone.0042992. Epub 2012 Sep 4.
BACKGROUND
The aim of this study was to identify a biomarker useful in the diagnosis and therapy of ovarian malignant germ cell tumor (OMGCT).
METHODS
The karyopherin 2 (KPNA2) expression in OMGCT and normal ovarian tissue was determined by standard gene microarray assays, and further validated by a quantitative RT-PCR and immunohistochemistry. The correlation between KPNA2 expression in OMGCT and certain clinicopathological features were analyzed. Expression of SALL4, a stem cell marker, was also examined in comparison with KPNA2.
RESULTS
KPNA2 was found to be over-expressed by approximately eight-fold in yolk sac tumors and immature teratomas compared to normal ovarian tissue by microarray assays. Overexpression was detected in yolk sac tumors, immature teratomas, dysgerminomas, embryonal carcinomas, mature teratomas with malignant transformation and mixed ovarian germ cell tumors at both the transcription and translation levels. A positive correlation between KPNA2 and SALL4 expression at both the transcription level (R = 0.5120, P = 0.0125), and the translation level (R = 0.6636, P<0.0001), was presented. Extensive expression of KPNA2 was positively associated with pathologic type, recurrence and uncontrolled, ascitic fluid presence, suboptimal cytoreductive surgery necessity, resistance/refraction to initial chemotherapy, HCG level and SALL4 level in OMGCT patients. KPNA2 was found to be an independent factor for 5-year disease-free survival (DFS) of OMGCT (P = 0.02). The 5-year overall survival (OS) and DFS rate for KPNA2-low expression patients (88% and 79%, n = 48) were significantly higher than the OS and DFS rate for KPNA2-high expression patients (69% and 57.1%, n = 42)(P = 0.0151, P = 0.0109, respectively). The 5-year OS and DFS rate for SALL4-low expression patients (84% and 74%, n = 62) was marginally significantly higher than the high expression patients (78.6% and 71.4%, n = 28)(P = 0.0519, P = 0.0647, respectively).
CONCLUSIONS
KPNA2 is a potential candidate molecular marker and important prognostic marker in OMGCT patients.
背景
本研究旨在寻找一种对卵巢恶性生殖细胞肿瘤（OMGCT）的诊断和治疗有用的生物标志物。
方法
采用标准基因微阵列检测试剂盒检测 OMGCT 和正常卵巢组织中的核蛋白输入因子 2（KPNA2）表达，并通过定量 RT-PCR 和免疫组织化学进一步验证。分析 KPNA2 在 OMGCT 中的表达与某些临床病理特征的相关性。同时检测干细胞标志物 SALL4 的表达，并与 KPNA2 进行比较。
结果
通过微阵列检测试剂盒发现，卵黄囊瘤和未成熟畸胎瘤中 KPNA2 的表达水平约为正常卵巢组织的 8 倍。在转录和翻译水平上，KPNA2 在卵黄囊瘤、未成熟畸胎瘤、无性细胞瘤、胚胎癌、成熟畸胎瘤伴恶性转化和混合性卵巢生殖细胞肿瘤中均有表达。KPNA2 和 SALL4 的转录水平（R = 0.5120，P = 0.0125）和翻译水平（R = 0.6636，P<0.0001）呈正相关。在 OMGCT 患者中，KPNA2 的广泛表达与病理类型、复发、腹水存在、肿瘤减灭术不充分、对初始化疗的耐药/抵抗、HCG 水平和 SALL4 水平有关。KPNA2 是影响 OMGCT 患者 5 年无病生存率（DFS）的独立因素（P = 0.02）。KPNA2 低表达患者的 5 年总生存率（OS）和 DFS 率（88%和 79%，n = 48）明显高于 KPNA2 高表达患者（69%和 57.1%，n = 42）（P = 0.0151，P = 0.0109）。SALL4 低表达患者的 5 年 OS 和 DFS 率（84%和 74%，n = 62）略高于高表达患者（78.6%和 71.4%，n = 28）（P = 0.0519，P = 0.0647）。
结论
KPNA2 是 OMGCT 患者潜在的候选分子标志物和重要的预后标志物。
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