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Identification of Cystatin SN as a novel tumor marker for colorectal cancer.

Abstract
The goal of this study was to investigate Cystatin SN, a cysteine protease inhibitor, as a novel tumor marker for colorectal cancer (CRC). Gene expression profiles of mRNA from normal tissues and cancer cell lines were performed. Twenty-eight monoclonal antibodies for Cystatin SN were generated and serum Cystatin SN was quantified using ELISA in sera from 159 patients with CRC and 40 healthy controls. Cystatin SN was highly expressed in colon cancer cells. Employing a receiver-operating characteristic curve, we obtained an area under the curve of 0.708 for Cystatin SN, 0.819 for carcinoembryonic antigen (CEA) and 0.703 for carbohydrate antigen 19-9 (CA19-9). The combination assay of Cystatin SN, CEA and CA19-9 showed 62.9% sensitivity and 90.0% specificity. Especially, the sensitivity of the combination assay in stages I and II detection, in which stages curative operation would be possible, was improved over that of the assay testing only for CEA and CA19-9 (from 37.5 to 42.5% in stage I, from 49.0 to 60.8% in stage II). Furthermore, Western blot analysis revealed that Cystatin SN was increased in the urine from patients with CRC. Our results suggest the possibility of utilizing this novel tumor marker that can be tested in urine samples. These observations suggest that Cystatin SN in combination with CEA and CA19-9 is a useful tumor marker for detecting early stage CRC and that it is a unique urinary excretory protein, suggesting that Cystatin SN might be a novel candidate for use in mass screening for CRC.
AuthorsKyoko Yoneda, Hiroshi Iida, Hiroki Endo, Kunihiro Hosono, Tomoyuki Akiyama, Hirokazu Takahashi, Masahiko Inamori, Yasunobu Abe, Masato Yoneda, Koji Fujita, Shingo Kato, Yuichi Nozaki, Yasushi Ichikawa, Hiroshi Uozaki, Masashi Fukayama, Takahiro Shimamura, Tatsuhiko Kodama, Hiroyuki Aburatani, Chihiro Miyazawa, Keisuke Ishii, Naoki Hosomi, Mina Sagara, Masazumi Takahashi, Hideyuki Ike, Hiroaki Saito, Akihiko Kusakabe, Atsushi Nakajima
JournalInternational journal of oncology (Int J Oncol) Vol. 35 Issue 1 Pg. 33-40 (Jul 2009) ISSN: 1019-6439 [Print] Greece
PMID19513549 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Biomarkers, Tumor
  • CA-19-9 Antigen
  • CST1 protein, human
  • Carcinoembryonic Antigen
  • RNA, Messenger
  • Salivary Cystatins
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor (blood, genetics, metabolism, urine)
  • CA-19-9 Antigen (blood)
  • Carcinoembryonic Antigen (blood)
  • Case-Control Studies
  • Cell Line, Tumor
  • Colorectal Neoplasms (genetics, metabolism, pathology)
  • Early Detection of Cancer
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression Profiling (methods)
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mass Screening (methods)
  • Middle Aged
  • Neoplasm Staging
  • Oligonucleotide Array Sequence Analysis
  • Predictive Value of Tests
  • RNA, Messenger (metabolism)
  • ROC Curve
  • Salivary Cystatins (blood, genetics, metabolism, urine)
  • Sensitivity and Specificity
  • Up-Regulation

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