title: Dermokine as a novel biomarker for early-stage colorectal cancer.
abstract: BACKGROUND
  Colorectal cancer is a common disease that is usually detected at an advanced stage, because early-stage cancer is mostly asymptomatic and appropriate serologic biomarkers have not been established. We have previously identified dermokine (DK) as a peptide secreted by keratinocytes and we found that DK-β/γ was expressed in colorectal tumors. Therefore, we focused on DK-β/γ as a new candidate diagnostic serum marker for early colorectal cancer.
  
  
  METHODS
  DK-β/γ expression in human colorectal cancer cell lines and tissues was assessed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. We established an experimental enzyme-linked immunosorbent assay (ELISA) to detect DK-β/γ in the serum of colorectal cancer patients, and we compared the sensitivities of common diagnostic markers, carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, and serum p53 antibody (S-p53).
  
  
  RESULTS
  Immunohistochemical staining of colon tumor tissue with anti-DK monoclonal antibody (mAb) revealed that DK-β/γ was more commonly expressed in the early stages of colorectal cancer (Tis-T1; i.e., cancer in situ, intraepithelial or invasion of lamina propria [Tis]; tumor invades the submucosa [T1]) than in late-stage tumors (T2-T4; i.e., tumor invades the muscularis propria [T2]; tumor invades through the muscularis propria into the subserosa, or into the nonperitonealized pericolic or perirectal tissues [T3]; tumor directly invades other organs or structures and/or perforates visceral peritoneum [T4]). Serum DK-β/γ levels were determined in 130 patients with colorectal cancer and 25 healthy volunteers. Serum DK-β/γ was detected in 33.3% of patients with early colorectal cancer (Tis-T1), which was higher than the rates for S-p53 (24.2%), CEA (9.1%), and CA19-9 (0%). The serum DK-β/γ test was complementary to the other marker tests. Therefore, when the combined four-marker test (DK/CEA/CA19-9/S-p53) was carried out, the diagnostic sensitivity for Tis and T1 tumors reached 60.6%.
  
  
  CONCLUSIONS
  Serum DK-β/γ is the most promising of the existing tumor biomarkers for the diagnosis of early-stage colorectal cancer.
authors.affiliation: Department of Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Tagi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsui
authors.forename: Shojiro
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Sachi
authors.initials: S
authors.lastname: Hoshi
authors.forename: Toshiya
authors.initials: T
authors.lastname: Ochiai
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Kokuba
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kinoshita-Ida
authors.forename: Fumie
authors.initials: F
authors.lastname: Kisumi-Hayashi
authors.forename: Koji
authors.initials: K
authors.lastname: Morimoto
authors.forename: Toshio
authors.initials: T
authors.lastname: Imai
authors.forename: Issei
authors.initials: I
authors.lastname: Imoto
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
authors.forename: Eigo
authors.initials: E
authors.lastname: Otsuji
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D009367:Neoplasm Staging; D011506:Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; C495568:DMKN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins