3 research outputs found
Identification of Adipophilin as a Potential Plasma Biomarker for Colorectal Cancer Using Label-Free Quantitative Mass Spectrometry and Protein Microarray
酵素触媒における電荷リレー系 : カルボキシペプチダーゼYの活性中心残基の構成と機能
京都大学0048新制・課程博士博士(農学)甲第7876号農博第1034号新制||農||776(附属図書館)学位論文||H11||N3239(農学部図書室)UT51-99-G470京都大学大学院農学研究科農芸化学専攻(主査)教授 林 力丸, 教授 佐藤 文彦, 教授 江崎 信芳学位規則第4条第1項該当Doctor of Agricultural ScienceKyoto UniversityDA
Identification of adipophilin as a potential plasma biomarker for colorectal cancer using label-free quantitative mass spectrometry and protein microarray.
[Background]: The aim of this study was to identify a new plasma biomarker for use in early detection of colorectal cancer.[Methods]: Using the combination of hollow fiber membrane (HFM)-based low-molecular weight protein enrichment and two-dimensional image converted analysis of liquid chromatography and mass spectrometry (2DICAL), we compared the plasma proteome of 22 colorectal cancer patients with those of 21 healthy controls. An identified biomarker candidate was then validated in two larger cohorts [validation-1 (n = 210) and validation-2 (n = 113)] using a high-density reverse-phase protein microarray. [Results]: From a total of 53, 009 mass peaks, we identified 103 with an area under curve (AUC) value of 0.80 or higher that could distinguish cancer patients from healthy controls. A peak that increased in colorectal cancer patients, with an AUC of 0.81 and P value of 0.0004 (Mann–Whitney U test), was identified as a product of the PLIN2 gene [also known as perilipin-2, adipose differentiation-related protein (ADRP), or adipophilin]. An increase in plasma adipophilin was consistently observed in colorectal cancer patients, including those with stage I or stage II disease (P < 0.0001, Welch's t test). Immunohistochemical analysis revealed that adipophilin is expressed primarily in the basal sides of colorectal cancer cells forming polarized tubular structures, and that it is absent from adjacent normal intestinal mucosae. [Conclusions]: Adipophilin is a plasma biomarker potentially useful for the detection of early-stage colorectal cancer. [Impact]: The combination of HFM and 2DICAL enables the comprehensive analysis of plasma proteins and is ideal for use in all biomarker discovery studies