Dermokine as a novel biomarker for early-stage colorectal cancer
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- Tagi, T., Matsui, T., Kikuchi, S. et al. J Gastroenterol (2010) 45: 1201. doi:10.1007/s00535-010-0279-4
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.
KeywordsSerum markerDermokineColorectal cancerEarly stage
Carbohydrate antigen 19-9
Serum p53 antibody
Enzyme-linked immunosorbent assay
Stratified squamous epithelium
Cancer in situ, intraepithelial or invasion of lamina propria
Tumor invades the submucosa
Tumor invades the muscularis propria
Tumor invades through the muscularis propria into the subserosa, or into the nonperitonealized pericolic or perirectal tissues
Tumor directly invades other organs or structures and/or perforates visceral peritoneum. We followed the International Union Against Cancer (UICC) classification