Dermokine as a novel biomarker for early-stage colorectal cancer
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
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.
- Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71–96. CrossRef
- Levin B, Lieberman DA, McFarland B, Smith RA, Brooks D, Andrews KS, et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA Cancer J Clin. 2008;58:130–60. CrossRef
- Kuusela P, Jalanko H, Roberts P, Sipponen P, Mecklin JP, Pitkanen R, et al. Comparison of CA 19–9 and carcinoembryonic antigen (CEA) levels in the serum of patients with colorectal diseases. Br J Cancer. 1984;49:135–9.
- Zamcheck N, Pusztaszeri G. CEA, AFP and other potential tumor markers. CA Cancer J Clin. 1975;25:204–14. CrossRef
- Matsui T, Hayashi-Kisumi F, Kinoshita Y, Katahira S, Morita K, Miyachi Y, et al. Identification of novel keratinocyte-secreted peptides dermokine-alpha/-beta and a new stratified epithelium-secreted protein gene complex on human chromosome 19q13.1. Genomics. 2004;84:384–97. CrossRef
- Moffatt P, Salois P, St-Amant N, Gaumond MH, Lanctot C. Identification of a conserved cluster of skin-specific genes encoding secreted proteins. Gene. 2004;334:123–31. CrossRef
- Naso MF, Liang B, Huang CC, Song XY, Shahied-Arruda L, Belkowski SM, et al. Dermokine: an extensively differentially spliced gene expressed in epithelial cells. J Invest Dermatol. 2007;127:1622–31.
- Toulza E, Galliano MF, Jonca N, Gallinaro H, Mechin MC, Ishida-Yamamoto A, et al. The human dermokine gene: description of novel isoforms with different tissue-specific expression and subcellular location. J Invest Dermatol. 2006;126:503–6. CrossRef
- Tanami H, Tsuda H, Okabe S, Iwai T, Sugihara K, Imoto I, et al. Involvement of cyclin d3 in liver metastasis of colorectal cancer, revealed by genome-wide copy-number analysis. Lab Invest. 2005;85:1118–29. CrossRef
- Matsuda T, Fujii T, Saito Y, Nakajima T, Uraoka T, Kobayashi N, et al. Efficacy of the invasive/non-invasive pattern by magnifying chromoendoscopy to estimate the depth of invasion of early colorectal neoplasms. Am J Gastroenterol. 2008;103:2700–6. CrossRef
- Kudo S, Lambert R, Allen JI, Fujii H, Fujii T, Kashida H, et al. Nonpolypoid neoplastic lesions of the colorectal mucosa. Gastrointest Endosc. 2008;68:S3–47.
- Bodmer WF. Cancer genetics: colorectal cancer as a model. J Hum Genet. 2006;51:391–6. CrossRef
- Kinzler KW, Vogelstein B. Lessons from hereditary colorectal cancer. Cell. 1996;87:159–70. CrossRef
- Kondo Y, Issa JP. Epigenetic changes in colorectal cancer. Cancer Metastasis Rev. 2004;23:29–39. CrossRef
- Gold P, Freedman SO. Specific carcinoembryonic antigens of the human digestive system. J Exp Med. 1965;122:467–81. CrossRef
- Locker GY, Hamilton S, Harris J, Jessup JM, Kemeny N, Macdonald JS, et al. ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol. 2006;24:5313–27. CrossRef
- Koprowski H, Herlyn M, Steplewski Z, Sears HF. Specific antigen in serum of patients with colon carcinoma. Science. 1981;212:53–5. CrossRef
- Levine AJ. P53, the cellular gatekeeper for growth and division. Cell. 1997;88:323–31. CrossRef
- Sigal A, Rotter V. Oncogenic mutations of the p53 tumor suppressor: the demons of the guardian of the genome. Cancer Res. 2000;60:6788–93.
- Vousden KH. P53: death star. Cell. 2000;103:691–4. CrossRef
- Crawford LV, Pim DC, Bulbrook RD. Detection of antibodies against the cellular protein p53 in sera from patients with breast cancer. Int J Cancer. 1982;30:403–8. CrossRef
- Dermokine as a novel biomarker for early-stage colorectal cancer
Journal of Gastroenterology
Volume 45, Issue 12 , pp 1201-1211
- Cover Date
- Print ISSN
- Online ISSN
- Springer Japan
- Additional Links
- 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