Dermokine as a novel biomarker for early-stage colorectal cancer
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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.
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).
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%.
Serum DK-β/γ is the most promising of the existing tumor biomarkers for the diagnosis of early-stage colorectal cancer.
- Dermokine as a novel biomarker for early-stage colorectal cancer
Journal of Gastroenterology
Volume 45, Issue 12 , pp 1201-1211
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- Print ISSN
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- Springer Japan
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- Serum marker
- Colorectal cancer
- Early stage
- Industry Sectors
- Author Affiliations
- 1. Department of Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, 602-8566, Japan
- 2. Medical Top Track (MTT) Program, Medical Research Institute, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
- 3. Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan
- 4. Eisai Tsukuba Research Laboratories, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki, 300-2635, Japan
- 5. KAN Research Institute, Inc., Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan
- 6. Department of Breast and Endocrine Surgery, Graduate School of Medicine, Osaka University, Yamadaoka, Suita, Osaka, 565-0871, Japan
- 7. Department of Biochemistry, Graduate School of Medicine Osaka University, office 1-3 Yamadaoka, Suita, Osaka, 565-0871, Japan
- 8. Department of Human Genetics and Public Health, Graduate School of Medical Science, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan
- 9. Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan