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Identification of S100A8 and S100A9 as serological markers for colorectal cancer.

 Hye-Jung Kim  ;  Hyun Ju Kang  ;  Hanna Lee  ;  Seung-Taek Lee  ;  Myeong-Hee Yu  ;  Hoguen Kim  ;  Cheolju Lee 
 JOURNAL OF PROTEOME RESEARCH, Vol.8(3) : 1368-1379, 2009 
Journal Title
Issue Date
Adenosylhomocysteinase/blood ; Adenosylhomocysteinase/metabolism ; Amino Acid Sequence ; Biomarkers, Tumor/metabolism* ; Calgranulin A/blood ; Calgranulin A/metabolism* ; Calgranulin B/blood ; Calgranulin B/metabolism* ; Cell Line, Tumor ; Colorectal Neoplasms/metabolism* ; Electrophoresis, Gel, Two-Dimensional ; Humans ; Molecular Sequence Data ; NM23 Nucleoside Diphosphate Kinases/blood ; NM23 Nucleoside Diphosphate Kinases/metabolism ; Proteome/metabolism* ; RNA, Messenger/blood ; RNA, Messenger/metabolism ; Tandem Mass Spectrometry
Colorectal cancer ; DIGE ; S100A8 ; S100A9 ; Serological biomarker
In search of novel serological protein biomarkers for human colorectal cancer (CRC), we analyzed CRC tissues using two-dimensional difference in-gel electrophoresis (2D-DIGE) on a narrow range IPG strip (pH 5.5-6.7). By comparing tumor tissues with matched normal tissues in a pairwise manner (n = 6), we identified 34 up-regulated and 17 down-regulated spots with intensity changes greater than 2-fold (Student's t-test, p < 0.05). Expression of both mRNA and protein levels of four proteins, adenosylhomocysteinase, Nm23-H1, S100A8 and S100A9, in CRC tissues was further evaluated by semiquantitative RT-PCR and Western blot analysis. The results revealed that all four proteins were elevated in the tumor tissues. We also confirmed, by immunohistochemistry, that adenosylhomocysteinase and Nm23-H1 were overexpressed in tumor cell cytoplasm and that S100A8 and S100A9 proteins were strongly expressed in tumor infiltrating immune cells. Western blot analysis with fractionated plasma samples showed that S100A8 and S100A9 were significantly increased in the plasma of CRC patients (n = 77) and colorectal adenoma patients (n = 11), compared to healthy controls (n = 21). The area under a receiver operating characteristic (ROC) curve was 0.91 for S100A8 and 0.89 for S100A9, which was superior to the established tumor marker carcinoembryonic antigen with 0.78 for the area under the ROC curve. Some patients with inflammatory diseases such as pancreatitis also showed elevated levels of the proteins. Importantly, in comparison to the control group, both proteins showed a remarkable change at the early stage of cancer. Therefore, we suggest S100A8 and S100A9 as candidates for serological biomarkers in combination with other serum markers that aid CRC diagnosis.
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1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Kang, Hyun Ju(강현주)
Kim, Hogeun(김호근)
Lee, Hanna(이한나)
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