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学科主题: 临床医学
题名:
Proteomic Expression Signature Distinguishes Cancerous and Nonmalignant Tissues in Hepatocellular Carcinoma
作者: Lee, Nikki P.1; Chen, Lei1,3; Lin, Marie C.2; Tsang, Felice H.1; Yeung, Chun1; Poon, Ronnie T.1; Peng, Jirun3; Leng, Xisheng3; Beretta, Laura4; Sun, Stella1; Day, Philip J.5; Luk, John M.1
关键词: hepatocellular carcinoma ; tumor markers ; proteomics ; diagnosis and prognosis
刊名: JOURNAL OF PROTEOME RESEARCH
发表日期: 2009-03-01
DOI: 10.1021/pr800637z
卷: 8, 期:3, 页:1293-1303
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemical Research Methods
研究领域[WOS]: Biochemistry & Molecular Biology
关键词[WOS]: HEAT-SHOCK PROTEINS ; CATHEPSIN-B ; ALPHA-FETOPROTEIN ; PROGESTERONE-RECEPTOR ; CLINICAL-IMPLICATIONS ; CHRONIC HEPATITIS ; CYTOCHROME B(5) ; LIVER-CIRRHOSIS ; SERUM ; MARKER
英文摘要:

Hepatocellular carcinoma (HCC) is an aggressive liver cancer but clinically validated biomarkers that can predict natural history of malignant progression are lacking. The present study explored the proteome-wide patterns of HCC to identify biomarker signature that could distinguish cancerous and nonmalignant liver tissues. A retrospective cohort of 80 HBV-associated HCC was included and both the tumor and adjacent nontumor tissues were subjected to proteome-wide expression profiling by 2-DE method. The subjects were randomly divided into the training (n = 55) and validation (n = 25) subsets, and the data analyzed by classification-and-regression tree algorithm. Protein markers were characterized by MALDI-ToF/MS and confirmed by immunohistochemistry, Western blotting and qPCR assays. Proteomic expression signature composed of six biomarkers (haptoglobin, cytochrome b5, progesterone receptor membrane component 1, heat shock 27 kDa protein 1, lysosomal proteinase cathepsin B, keratin 1) was developed as a classifier model for predicting HCC. We further evaluated the model using both leave-one-out procedure and independent validation, and the overall sensitivity and specificity for HCC both are 92.5%, respectively. Clinical correlation analysis revealed that these biomarkers were significantly associated with serum AFP, total protein levels and the Ishak′s score. The described model using biomarker signatures could accurately distinguish HCC from nonmalignant tissues, which may also provide hints on how normal hepatocytes are transformed to malignant state during tumor progression.

语种: 英语
所属项目编号: N_HKU 718/03 ; ITS/120/07
项目资助者: Council of Hong Kong ; Innovation and Technology Fund ; Sun Chieh Yeh Research Foundation for Hepatobiliary and Pancreatic Surgery
WOS记录号: WOS:000264035000019
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63967
Appears in Collections:北京大学第二临床医学院_期刊论文

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作者单位: 1.Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA
2.Univ Hong Kong, Dept Surg, Ctr Canc Res, Hong Kong, Hong Kong, Peoples R China
3.Univ Hong Kong, Dept Chem, Hong Kong, Hong Kong, Peoples R China
4.Peking Univ, Dept Surg, Peoples Hosp, Beijing 100871, Peoples R China
5.Univ Manchester, Manchester Interdisciplinary Bioctr, Manchester, Lancs, England

Recommended Citation:
Lee, Nikki P.,Chen, Lei,Lin, Marie C.,et al. Proteomic Expression Signature Distinguishes Cancerous and Nonmalignant Tissues in Hepatocellular Carcinoma[J]. JOURNAL OF PROTEOME RESEARCH,2009,8(3):1293-1303.
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