Selected reaction monitoring for colorectal cancer diagnosis using a set of five serum peptides identified by BLOTCHIP®-MS analysis
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Colorectal cancer (CRC) is one of the most predominant types of cancer, and it is the fourth most common cause of cancer-related death and it is important to diagnose CRC in early stage to decrease the mortality by CRC. In our previous study, we identified a combination of five peptides as a biomarker candidate to diagnose CRC by BLOTCHIP®-MS analysis using a set of healthy control subjects and CRC patients (stage II–IV). The aim of the present study was to validate the serum biomarker peptides reported in our previous study using a second cohort and to establish their potential usefulness in CRC diagnosis.
A total of 56 patients with CRC (n = 14 each of stages I–IV), 60 healthy controls, and 60 patients with colonic adenoma were included in this study. The five peptides were extracted and analyzed by selected reaction monitoring using ProtoKey® Colorectal Cancer Risk Test Kit (Protosera, Inc., Amagasaki, Japan).
The results clearly showed that the four CRC groups, stages I–IV, could be sufficiently discriminated from the control group and colonic polyp group. This five-peptide set could identify CRC at each stage compared to the control population in this validation cohort, including those with early-stage disease. The AUC values for each stage of CRC compared to the control population were 0.779, 0.946, 0.852, and 0.973 for stages I, II, III, and IV, respectively.
In this case–control validation study, we confirmed high diagnostic performance for CRC using five peptides that were identified in our previous study as serum biomarker candidates for the detection of CRC.
KeywordsColorectal cancer Biomarker Peptidome BLOTCHIP®-MS analysis
This work was supported by Grants-in-Aid for Scientific Research (KAKENHI) (B) to Y.N. (No. 16H05289) from the Japan Society for the Promotion of Science (JSPS), and by an Adaptable and Seamless Technology Transfer Program through target-driven R&D (to Y.N.) from the Japan Agency for Medical Research and Development (AMED), a Grant-in-Aid for Scientific Research (KAKENHI) (C) to K.U. (No. 15K08313) from the Japan Society for the Promotion of Science (JSPS), a Grant-in-Aid for Scientific Research (KAKENHI) (C) to T.T. (No. 16K09322) from the Japan Society for the Promotion of Science (JSPS). Statistical analysis was assisted by Hajime Yamakage (Satista Co., Ltd.).
Designed the experiments and wrote the paper: YN, NA, and KU. Analyzed the data: YN, NA, DN, KA, L-J L, KT and KU. Sample collection: YN, NA, KU, TO, NY, KK, KK, OH, TI, TT, HK, YK, NM, EO, and YI. Manipulation of samples: KM, YH, and YH. Overall supervision: NA, YN, and YI. All authors read and approved the final manuscript.
- 4.Edwards BK, Ward E, Kohler BA, et al. Annual report to the nation on the status of cancer, 1975-2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer. 2010;116(3):544–73 Epub 2009/12/10.CrossRefPubMedPubMedCentralGoogle Scholar
- 22.Uchiyama K, Naito Y, Yagi N, et al. Peptidomic analysis via one-step direct transfer technology for colorectal cancer biomarker discovery. J Proteomics Bioinform. 2015;5:1.Google Scholar
- 24.World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. Seoul: From the 59th World Medical Association Assembly [database on the internet]. 2008. http://www.wma.net/en/30publications/10policies/b3/17c.pdf.
- 25.Team RC. R: A language and environment for statistical computing. R Foundation for Statistical Computing. 2014.Google Scholar
- 26.Bendix Carstensen MP, Esa Laara, Michael Hills. Epi: A package for statistical analysis in epidemiology. R package version 1.1.67. 2015.Google Scholar