Dermokine as a novel biomarker for early-stage colorectal cancer

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-beta/gamma was expressed in colorectal tumors. Therefore, we focused on DK-beta/gamma as a new candidate diagnostic serum marker for early colorectal cancer. DK-beta/gamma 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-beta/gamma 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-beta/gamma 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-beta/gamma levels were determined in 130 patients with colorectal cancer and 25 healthy volunteers. Serum DK-beta/gamma 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-beta/gamma 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-beta/gamma is the most promising of the existing tumor biomarkers for the diagnosis of early-stage colorectal cancer.