High Levels of Nucleolar Expression of Nucleolin Are Associated with Better Prognosis in Patients with Stage II Pancreatic Ductal Adenocarcinoma

High Levels of Nucleolar Expression of Nucleolin Are Associated with Better Prognosis in Patients with Stage II Pancreatic Ductal Adenocarcinoma
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DOI:
10.1158/1078-0432.ccr-09-3411
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发表时间:
2010-07-15
影响因子:
11.5
通讯作者:
Wang, Huamin
Wang, Huamin
中科院分区:
医学1区
文献类型:
--
作者:
Peng, Lan;Liang, John;Wang, Huamin

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目的:核仁素是一种主要的核仁蛋白,已被证明在快速分裂的细胞中过表达,并在细胞增殖和存活中起重要作用。然而,核仁素在胰腺导管腺癌(PDA)的表达和意义还没有研究。实验设计:我们使用了一个组织微阵列组成的1.0毫米的核心肿瘤和配对的非肿瘤胰腺组织从69 pancreaticostomy标本与第二阶段PDA。核仁素的表达通过免疫组织化学和图像分析定量评分。核仁素表达被分类为核仁素-高或核仁素-低,使用中值核仁素标记指数3.5%作为截止。结果:PDAs和PDA细胞系均呈核仁染色,核仁蛋白染色阳性率分别为100%和100%。核仁素在PDA和PDA细胞系中的表达高于非肿瘤性导管上皮细胞。在69例II期PDA中,34例(49%)核仁素高。核仁素高的PDA患者的中位总生存期为65.2 +/- 16.3个月,而核仁素低的患者的中位总生存期为19.5 +/- 3.3个月(P = 0.03,对数秩方法)。核仁素的表达和其他临床病理参数之间没有显着的相关性被发现。在多变量分析中,核仁素的表达是一个预后因素,患者的年龄,性别,肿瘤的大小,分化,和淋巴结状态独立于患者的II期PDA患者的总生存期。结论:核仁素过表达的PDA和PDA细胞系。核仁素的高水平核仁表达是II期PDA患者生存率较好的独立预后标志。临床癌症研究; 16(14); 3734-42。(C)2010年AACR。
Purpose: Nucleolin is a major nucleolar protein that has been shown to be overexpressed in rapidly dividing cells and plays an essential role in cell proliferation and survival. However, the expression and significance of nucleolin in pancreatic ductal adenocarcinoma (PDA) have not been studied.Experimental Design: We used a tissue microarray consisting of 1.0-mm cores of tumor and paired nonneoplastic pancreatic tissue from 69 pancreaticoduodenectomy specimens with stage II PDA. Nucleolin expression was evaluated by immunohistochemistry and scored quantitatively by image analysis. Nucleolin expression was classified as nucleolin-high or nucleolin-low using the median nucleolin labeling index of 3.5% as cutoff. Staining results were correlated with clinicopathologic features and survival.Results: Both PDAs and PDA cell lines showed nucleolar staining for nucleolin. Nucleolin expression was higher in PDAs and PDA cell lines than in nonneoplastic ductal epithelial cells. Among the 69 stage II PDAs, 34 (49%) were nucleolin-high. The median overall survival was 65.2 +/- 16.3 months for patients who had nucleolin-high PDAs compared with 19.5 +/- 3.3 months for patients whose tumors were nucleolin-low (P = 0.03, log-rank method). No significant correlation between nucleolin expression and other clinicopathologic parameters was found. In multivariate analysis, nucleolin expression was a prognostic factor for overall survival in patients with stage II PDA independent of patient's age, gender, tumor size, differentiation, and lymph node status.Conclusions: Nucleolin was overexpressed in PDAs and PDA cell lines. A high level of nucleolar expression of nucleolin was an independent prognostic marker for better survival for patients with stage II PDAs. Clin Cancer Res; 16(14); 3734-42. (C)2010 AACR.