title: 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.
authors.affiliation: Gastroenterology Division, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Yoneda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iida
authors.forename: Hiroki
authors.initials: H
authors.lastname: Endo
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Hosono
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Akiyama
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Takahashi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Inamori
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Abe
authors.forename: Masato
authors.initials: M
authors.lastname: Yoneda
authors.forename: Koji
authors.initials: K
authors.lastname: Fujita
authors.forename: Shingo
authors.initials: S
authors.lastname: Kato
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Nozaki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ichikawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uozaki
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shimamura
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Chihiro
authors.initials: C
authors.lastname: Miyazawa
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ishii
authors.forename: Naoki
authors.initials: N
authors.lastname: Hosomi
authors.forename: Mina
authors.initials: M
authors.lastname: Sagara
authors.forename: Masazumi
authors.initials: M
authors.lastname: Takahashi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ike
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Saito
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kusakabe
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakajima
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D018395:CA-19-9 Antigen / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055088:Early Detection of Cancer; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000378:metabolism; D012372:ROC Curve; D055333:Salivary Cystatins / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D012680:Sensitivity and Specificity; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; C525171:CST1 protein, human; D002272:Carcinoembryonic Antigen; D012333:RNA, Messenger; D055333:Salivary Cystatins