演題

RS1-16-9-3

大腸癌におけるα1-6フコース転移酵素とp53

[演者] 岡山 洋和:1
[著者] 野田 勝:3, 芦澤 舞:1, 中島 隆宏:1, 青砥 慶太:1, 千田 峻:1, 小船戸 康英:2, 大木 進司:1, 丸橋 繁:2, 河野 浩二:1
1:福島県立医科大学医学部 消化管外科学講座, 2:福島県立医科大学医学部 肝胆膵・移植外科学講座, 3:福島県立医科大学医学部 乳腺外科学講座

Colorectal cancer (CRC) is a molecularly heterogeneous disease with diverse clinical behaviors. During carcinogenesis, CRC cell surface glycans are known to undergo drastic changes, which can be attributed to dysregulation of multiple glycosyltransferases, contributing to distinct biological functions and unique tumor phenotypes. We conducted comprehensive glycosyltransferase gene expression analyses using multiple datasets, consisting of more than 940 samples based on microarray and RNA-sequence. This led us to identify a genomically distinct subclass with poor outcomes, in which the expression of α1-6 fucosyltransferase gene was upregulated. Also, this gene was consistently highly expressed in wild-type P53 tumors compared to that of mutant P53 in three independent datasets, containing approximately 700 samples. Immunohistochemistry (IHC) for α1-6 fucosyltransferase was performed in CRC specimens obtained from 335 patients who underwent surgery in our department. However, the protein expression of α1-6 fucosyltransferase was not associated with any of clinicopathological features, and it had no significant impact on patient survival. No association was found between α1-6 fucosyltransferase and the P53 status determined by the nuclear accumulation of P53 protein, and the P53 status itself was not prognostic in our cohort. Strikingly, when stage II and III patients were stratified according to the P53 status, positive staining of α1-6 fucosyltransferase was significantly associated with better overall survival only in tumors with negative P53, while it was marginally correlated with even worse survival in positive P53 tumors. Similar prognostic effect were observed in analyses of cancer-specific and disease-free survival. Collectively, our results suggest that the expression of α1-6 fucosyltransferase can be a biomarker for patients with stage II and III CRC, and its prognostic value may be highly dependent upon the status of P53.
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