Identification of Cystatin SN as a novel tumor marker for colorectal cancer.
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.
Yoneda
Kyoko
K
Gastroenterology Division, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama 236-0004, Japan.
Iida
Hiroshi
H
Endo
Hiroki
H
Hosono
Kunihiro
K
Akiyama
Tomoyuki
T
Takahashi
Hirokazu
H
Inamori
Masahiko
M
Abe
Yasunobu
Y
Yoneda
Masato
M
Fujita
Koji
K
Kato
Shingo
S
Nozaki
Yuichi
Y
Ichikawa
Yasushi
Y
Uozaki
Hiroshi
H
Fukayama
Masashi
M
Shimamura
Takahiro
T
Kodama
Tatsuhiko
T
Aburatani
Hiroyuki
H
Miyazawa
Chihiro
C
Ishii
Keisuke
K
Hosomi
Naoki
N
Sagara
Mina
M
Takahashi
Masazumi
M
Ike
Hideyuki
H
Saito
Hiroaki
H
Kusakabe
Akihiko
A
Nakajima
Atsushi
A
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
D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; C525171:CST1 protein, human; D002272:Carcinoembryonic Antigen; D012333:RNA, Messenger; D055333:Salivary Cystatins