Dermokine as a novel biomarker for early-stage colorectal cancer.
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.
Tagi
Tomoyuki
T
Department of Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, 602-8566, Japan.
Matsui
Takeshi
T
Kikuchi
Shojiro
S
Hoshi
Sachi
S
Ochiai
Toshiya
T
Kokuba
Yukihito
Y
Kinoshita-Ida
Yoko
Y
Kisumi-Hayashi
Fumie
F
Morimoto
Koji
K
Imai
Toshio
T
Imoto
Issei
I
Inazawa
Johji
J
Otsuji
Eigo
E
D014408:Biomarkers, Tumor / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D009367:Neoplasm Staging; D011506:Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; C495568:DMKN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins