Dermokine as a novel biomarker for early-stage colorectal cancer

被引:25
作者
Tagi, Tomoyuki [1 ]
Matsui, Takeshi [2 ]
Kikuchi, Shojiro [1 ,3 ]
Hoshi, Sachi [4 ]
Ochiai, Toshiya [1 ]
Kokuba, Yukihito [1 ]
Kinoshita-Ida, Yoko [5 ]
Kisumi-Hayashi, Fumie [5 ]
Morimoto, Koji [6 ,7 ]
Imai, Toshio [5 ]
Imoto, Issei [8 ,9 ]
Inazawa, Johji [9 ]
Otsuji, Eigo [1 ]
机构
[1] Kyoto Prefectural Univ Med, Dept Surg, Kamigyo Ku, Kyoto 6028566, Japan
[2] Tokyo Med & Dent Univ, Med Res Inst, MTT Program, Bunkyo Ku, Tokyo 1138510, Japan
[3] Hyogo Coll Med, Dept Surg, Nishinomiya, Hyogo 6638501, Japan
[4] Eisai & Co Ltd, Eisai Tsukuba Res Labs, Tsukuba, Ibaraki 3002635, Japan
[5] KAN Res Inst Inc, Chuo Ku, Kobe, Hyogo 6500047, Japan
[6] Osaka Univ, Grad Sch Med, Dept Breast & Endocrine Surg, Suita, Osaka 5650871, Japan
[7] Osaka Univ, Grad Sch Med, Dept Biochem, Suita, Osaka 5650871, Japan
[8] Univ Tokushima, Grad Sch Med Sci, Dept Human Genet & Publ Hlth, Tokushima 7708503, Japan
[9] Tokyo Med & Dent Univ, Dept Mol Cytogenet, Med Res Inst, Bunkyo Ku, Tokyo 1138510, Japan
关键词
Serum marker; Dermokine; Colorectal cancer; Early stage; P53; GENE; IDENTIFICATION; ANTIGEN; GENOME; SERUM;
D O I
10.1007/s00535-010-0279-4
中图分类号
R57 [消化系及腹部疾病];
学科分类号
100201 [内科学];
摘要
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.
引用
收藏
页码:1201 / 1211
页数:11
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