title: Dikkopf-1 as a novel serologic and prognostic biomarker for lung and esophageal carcinomas.
abstract: Gene expression profile analysis of lung and esophageal carcinomas revealed that Dikkopf-1 (DKK1) was highly transactivated in the great majority of lung cancers and esophageal squamous cell carcinomas (ESCC). Immunohistochemical staining using tumor tissue microarrays consisting of 279 archived non-small cell lung cancers (NSCLC) and 280 ESCC specimens showed that a high level of DKK1 expression was associated with poor prognosis of patients with NSCLC as well as ESCC, and multivariate analysis confirmed its independent prognostic value for NSCLC. In addition, we identified that exogenous expression of DKK1 increased the migratory activity of mammalian cells, suggesting that DKK1 may play a significant role in progression of human cancer. We established an ELISA system to measure serum levels of DKK1 and found that serum DKK1 levels were significantly higher in lung and esophageal cancer patients than in healthy controls. The proportion of the DKK1-positive cases was 126 of 180 (70.0%) NSCLC, 59 of 85 (69.4%) SCLC, and 51 of 81 (63.0%) ESCC patients, whereas only 10 of 207 (4.8%) healthy volunteers were falsely diagnosed as positive. A combined ELISA assays for both DKK1 and carcinoembryonic antigen increased sensitivity and classified 82.2% of the NSCLC patients as positive whereas only 7.7% of healthy volunteers were falsely diagnosed to be positive. The use of both DKK1 and ProGRP increased sensitivity to detect SCLCs up to 89.4%, whereas false-positive rate in healthy donors was only 6.3%. Our data imply that DKK1 should be useful as a novel diagnostic/prognostic biomarker in clinic and probably as a therapeutic target for lung and esophageal cancer.
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Yamabuki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takano
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hayama
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Ishikawa
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kato
authors.forename: Masaki
authors.initials: M
authors.lastname: Miyamoto
authors.forename: Tomoo
authors.initials: T
authors.lastname: Ito
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ito
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyagi
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Nakayama
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujita
authors.forename: Masao
authors.initials: M
authors.lastname: Hosokawa
authors.forename: Eiju
authors.initials: E
authors.lastname: Tsuchiya
authors.forename: Nobuoki
authors.initials: N
authors.lastname: Kohno
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kondo
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yataro
authors.initials: Y
authors.lastname: Daigo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D004938:Esophageal Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D008175:Lung Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins