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

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.

Complement Component 3 (C3) Concentrations in Cancer Patients: A Systematic Review and Meta-Analysis

“…Experimentally, it was reported that complement C3 can be considered as an early diagnostic marker for some type of cancers [40,44,45]. The above described research supports the results of our metaanalysis from different angles, indicating that our analytical results are reliable.…”

Modelling biological age based on plasma peptides in Han Chinese adults

“…As in previous studies [ 27 , 28 , 43 ], all plasma samples were fractionated using weak cation exchange magnetic beads to gather and enrich the proteins or peptides, according to the instructions provided by the supplier (ClinProt™, Bruker Daltonics, Billerica, USA) [ 44 , 45 ]. The samples were purified and isolated through three steps: binding, washing, and elution.…”

“…Plasma peptides, such as hormones, cytokines and growth factors, promote homeostasis in many biological processes [26]. Additionally, some plasma peptides have been found to be associated with age-related diseases, including Alzheimer's disease, hypertension, type 2 diabetes, and colorectal cancer [27][28][29][30][31]. Furthermore, our previous study shows that some peptides are highly correlated with chronological age in a Chinese population, such as fragment of apolipoprotein A-I, fibrinogen alpha, albumin and so on [19].…”

The Relevance of Mass Spectrometry Analysis for Personalized Medicine through Its Successful Application in Cancer “Omics”

“…The identification of these peptides was performed using LC-MS/MS. Notably; MALDI-TOF MS and LC-MS/MS were applied to analyze; diagnose human disease and identify potential biomarkers of health status using biosamples such as serum/plasma; saliva and urine [110].…”