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Fatty Acid Binding Protein 6 Is Overexpressed in Colorectal Cancer

Authors' Affiliations: ¹ Department of Surgery and Molecular Oncology, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan; ² Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama, Japan; ³ Department of Surgery, Jikei University School of Medicine, Minato-ku, Tokyo, Japan; and ⁴ Department of Biochemistry, Niigata University School of Medicine, Niigata, Japan

Requests for reprints: Masaki Mori, Department of Surgery and Molecular Oncology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu 874-0838, Japan. Phone: 81-977-1645; Fax: 81-977-1651; E-mail: mmori{at}beppu.kyushu-u.ac.jp.

Purpose: Fatty acid binding protein 6 (FABP6) is a cancer-related protein that acts as an intracellular transporter of bile acid in the ileal epithelium. Because bile acids are implicated in the carcinogenesis of colorectal cancer, we evaluated FABP6 expression in colorectal cancer.

Experimental Design: The expression of FABP6 mRNA was evaluated in 78 paired samples of cancer/normal tissue representing colorectal cancer cases, plus 16 adenomas, and 16 metastatic lymph nodes. An immunohistochemical study was conducted with paraffin sections. In vitro transfection was done to determine FABP6's biological roles.

Results: The expression of FABP6 mRNA was significantly higher in cancer (75 of 78, 96.2%) than in normal tissue (P < 0.001). The expression of mRNA was increased in cancer compared with adenoma, but was dramatically decreased in node metastases. Tumors with high FABP6 expression were smaller in size (P < 0.01), more often in the left colon (P < 0.05), and had shallower invasion into the bowel wall (P < 0.05) compared with those with low expression. There was no significant difference between high- and low-expression tumors regarding clinicopathologic variables such as histologic type, lymph node, or liver metastasis, Dukes' classification, and prognosis. Immunohistochemical study revealed that FABP6 expression was primarily observed in cancer cells. In vitro transfection revealed that transfectants showed weaker invasiveness (P < 0.05), more dominant proliferation (P < 0.001), and less apoptosis than mock cells.

Conclusions: The expression of FABP6 was higher in primary colorectal cancers and adenomas than in normal epithelium, but was dramatically decreased in lymph node metastases, suggesting that FABP6 may play an important role in early carcinogenesis.

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