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Serum metabolomics analysis for early detection of colorectal cancer
Authors:Kazuhiko?Uchiyama  Nobuaki?Yagi  Katsura?Mizushima  Yasuki?Higashimura  Yasuko?Hirai  Tetsuya?Okayama  Naohisa?Yoshida  Kazuhiro?Katada  Kazuhiro?Kamada  Osamu?Handa  Takeshi?Ishikawa  Tomohisa?Takagi  Hideyuki?Konishi  Yoshiaki?Kuriu  Masayoshi?Nakanishi  Eigo?Otsuji  Yoshito?Itoh  Email author" target="_blank">Yuji?NaitoEmail author
Institution:1.Molecular Gastroenterology and Hepatology,Kyoto Prefectural University of Medicine,Kyoto,Japan;2.Department of Endoscopy and Ultrasound Medicine,Kyoto Prefectural University of Medicine,Kyoto,Japan;3.Department of Gastroenterology,Murakami Memorial Hospital, Asahi University,Gifu,Japan;4.Department of Surgery, Division of Digestive Surgery,Kyoto Prefectural University of Medicine,Kyoto,Japan
Abstract:

Background

Although colorectal cancer (CRC) is one of the most common causes of cancer mortality, early-stage detection improves survival rates dramatically. Because cancer impacts important metabolic pathways, the alteration of metabolite levels as a potential biomarker of early-stage cancer has been the focus of many studies. Here, we used CE-TOFMS, a novel and promising method with small injection volume and high resolution, to separate and detect ionic compounds based on the different migration rates of charged metabolites in order to detect metabolic biomarkers in patients with CRC.

Methods

A total of 56 patients with CRC (n = 14 each of Stages I-IV), 60 healthy controls, and 59 patients with colonic adenoma were included in this study. Metabolome analysis was conducted by CE-TOFMS on serum samples of patients and controls using the Advanced Scan package (Human Metabolome Technologies).

Results

We obtained 334 metabolites in the serum, of which 139 were identified as known substances. Among these 139 known metabolites, 16 were correlated with CRC stage by upregulation and 44 by downregulation, with benzoic acid (r = ?0.649, t = 11.653, p = 6.07599E?24), octanoic acid (r = 0.557, t = 9.183, p = 7.9557E?17), decanoic acid (r = 0.539, t = 8.749, p = 1.24352E?15), and histidine (r = ?0.513, t = 8.194, p = 3.90224E?14) exhibiting significant correlation.

Conclusions

To the best of our knowledge, this is the first report to determine the correlation between serum metabolites and CRC stage using CE-TOFMS. Our results show that benzoic acid exhibited excellent diagnostic power and could potentially serve as a novel disease biomarker for CRC diagnosis.
Keywords:
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