Original Article—Alimentary Tract

Journal of Gastroenterology

, Volume 45, Issue 12, pp 1201-1211

Dermokine as a novel biomarker for early-stage colorectal cancer

  • Tomoyuki TagiAffiliated withDepartment of Surgery, Kyoto Prefectural University of Medicine
  • , Takeshi MatsuiAffiliated withMedical Top Track (MTT) Program, Medical Research Institute, Tokyo Medical and Dental University
  • , Shojiro KikuchiAffiliated withDepartment of Surgery, Kyoto Prefectural University of MedicineDepartment of Surgery, Hyogo College of Medicine Email author 
  • , Sachi HoshiAffiliated withEisai Tsukuba Research Laboratories, Eisai Co., Ltd.
  • , Toshiya OchiaiAffiliated withDepartment of Surgery, Kyoto Prefectural University of Medicine
  • , Yukihito KokubaAffiliated withDepartment of Surgery, Kyoto Prefectural University of Medicine
  • , Yoko Kinoshita-IdaAffiliated withKAN Research Institute, Inc.
  • , Fumie Kisumi-HayashiAffiliated withKAN Research Institute, Inc.
  • , Koji MorimotoAffiliated withDepartment of Breast and Endocrine Surgery, Graduate School of Medicine, Osaka UniversityDepartment of Biochemistry, Graduate School of Medicine Osaka University
    • , Toshio ImaiAffiliated withKAN Research Institute, Inc.
    • , Issei ImotoAffiliated withDepartment of Human Genetics and Public Health, Graduate School of Medical Science, The University of TokushimaDepartment of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University
    • , Johji InazawaAffiliated withDepartment of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University
    • , Eigo OtsujiAffiliated withDepartment of Surgery, Kyoto Prefectural University of Medicine

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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.

Keywords

Serum marker Dermokine Colorectal cancer Early stage