Serum peptidome profiling for the diagnosis of colorectal cancer: discovery and validation in two independent cohorts

// Hao Wang 1, * , Chenghua Luo 2, * , Shengtao Zhu 3, 4 , Honghong Fang 1 , Qing Gao 1 , Siqi Ge 1, 5 , Haixia Qu 6 , Qingwei Ma 6 , Hongwei Ren 7 , Youxin Wang 1 and Wei Wang 1, 5 1 Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China 2 Department of Retroperitoneal Tumors Surgery, Peking University International Hospital, Beijing 102206, China 3 Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing 100069, China 4 National Center for Clinical Medical Research of Digestive Diseases, Beijing 100069, China 5 School of Medical and Health Sciences, Edith Cowan University, Perth 6027, Australia 6 Bioyong (Beijing) Technology Co., Ltd., Beijing 100085, China 7 School of Life Sciences, Peking University, Beijing 100871, China * These authors have contributed equally to this work Correspondence to: Wei Wang, email: wei.wang@ecu.edu.au Youxin Wang, email: wangy@ccmu.edu.cn Keywords: colorectal cancer, peptidome, MALDI-TOF MS, diagnosis panel Received: May 18, 2017     Accepted: June 29, 2017     Published: July 26, 2017 ABSTRACT Colorectal cancer (CRC) is one of the most common malignant neoplasms worldwide. Except for the existing fecal occult blood test, colonoscopy and sigmoidoscopy, no widely accepted in vitro diagnostic methods have been available. To identify potential peptide biomarkers for CRC, serum samples from a discovery cohort (100 CRC patients and 100 healthy controls) and an independent validation cohort (91 CRC patients and 91 healthy controls) were collected. Peptides were fractionated by weak cation exchange magnetic beads (MB-WCX) and analysed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Five peptides (peaks at m/z 1895.3, 2020.9, 2080.7, 2656.8 and 3238.5) were identified as candidate biomarkers for CRC. A diagnostic panel based on the five peptides can discriminate CRC patients from healthy controls, with an accuracy of 91.8%, sensitivity of 95.6%, and specificity of 87.9% in the validation cohort. Peptide peaks at m/z 1895.3, 2020.9 and 3238.5 were identified as the partial sequences of complement component 4 (C4), complement component 3 (C3) and fibrinogen α chain (FGA), respectively. This study potentiated peptidomic analysis as a promising in vitro diagnostic tool for diagnosis of CRC. The identified peptides suggest the involvement of the C3, C4 and FGA in CRC pathogenesis.