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学科主题: 临床医学
题名:
Association of mortalin (HSPA9) with liver cancer metastasis and prediction for early tumor recurrence
作者: Yi, Xin1,2; Luk, John M.1; Lee, Nikki P.1; Peng, Jirun2; Leng, Xisheng2; Guan, Xin-Yuan1; Lau, George K.3; Beretta, Laura4; Fan, Sheung-Tat1
刊名: MOLECULAR & CELLULAR PROTEOMICS
发表日期: 2008-02-01
DOI: 10.1074/mcp.M700116-MCP200
卷: 7, 期:2, 页:315-325
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]: HSP70 FAMILY-MEMBER ; HEPATOCELLULAR-CARCINOMA ; HEPATITIS-C ; ALPHA-FETOPROTEIN ; UP-REGULATION ; BIOMARKER DISCOVERY ; IDENTIFICATION ; EXPRESSION ; PROTEINS ; DISEASE
英文摘要:

Hepatocellular carcinoma (HCC) is well known for poor prognosis and short survival because of high recurrence rate even after curative surgery. Today there is no available biomarker or biochemical test to indicate HCC recurrence, and this study aims to identify protein markers that can discriminate postoperative patients with early recurrence (ER), i.e. disease relapsed within the first year. In this study, 103 hepatitis B-related HCC patients were recruited, and 68 of them were used for ER-related biomarker discovery study. Proteomic expression patterns of matched tumor and adjacent non-tumor tissues from these patients plus 16 normal liver tissues were delineated by the two-dimensional gel electrophoresis differential profiling method. Significant protein spots were evaluated by hierarchical clustering analysis. SSP4612 that yielded the highest receiver operating characteristic (ROC) curve value for the ER subgroup of HCC was subsequently identified by tandem mass spectrometry, and the corresponding expression patterns were further confirmed by quantitative PCR, Western blot, and immunohistochemistry. Correlation analysis with clinicopathological data was also examined. Proteomic profiling analysis revealed overexpression of mortalin (gene HSPA9) in HCC when compared with the non-tumor and normal liver tissues (area under the curve (AUC) = 0.821). Furthermore, elevated mortalin level was also detected in the ER subgroup of HCC versus the recurrence-free state (where no cancer recurs for >1 year) (AUC = 0.833, sensitivity = 90.9%, specificity = 71.4%). Metastatic HCC cell lines also exhibited higher levels of mortalin and HSPA9 mRNA. Clinically, mortalin overexpression in HCC was closely associated with advanced tumor stages and venous infiltration, having implications for increased malignancy and aggressive behavior. Mortalin (HSPA9) is associated with HCC metastasis and thus suggested as a tumor marker for predicting early recurrence, which may have immediate clinical applications for cancer surveillance after curative surgery.

语种: 英语
WOS记录号: WOS:000253417300009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50520
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.Univ Hong Kong, Dept Surg, Pokfulam, Hong Kong, Peoples R China
2.Peking Univ, Peoples Hosp, Dept Surg, Beijing 100871, Peoples R China
3.Univ Hong Kong, Jockey Club Clin Res Ctr, Pokfulam, Hong Kong, Peoples R China
4.Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA

Recommended Citation:
Yi, Xin,Luk, John M.,Lee, Nikki P.,et al. Association of mortalin (HSPA9) with liver cancer metastasis and prediction for early tumor recurrence[J]. MOLECULAR & CELLULAR PROTEOMICS,2008,7(2):315-325.
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