IDDF2018-ABS-0228 Human gut secretome profiling in malaysian adults: a case study on colorectal cancer

Abstract

Background Over the recent years, there has been a paradigm shift in the landscape of understanding colorectal cancer (CRC). Secretomics, a subset of oncoproteomics has emerged as an important tool for CRC biomarker discovery as tumours are known to secrete carcinogenic factors essential for cancer pathogenesis. However, secretomics studies in CRC had mainly focused on in-vitro human cell lines instead of direct assessment from the human gut. Therefore, we aim to identify the secreted proteins released from the human CRC-stricken gut by assessing the secretome in the stool samples. Methods Stools samples from 26 clinically-diagnosed CRC patients and 20 non-CRC control individuals were collected, homogenised and filtered followed by protein extraction and profiling by quantitative label-free proteomics using Nano-Liquid Chromatography TripleTOF Mass Spectrometry. The mass spectra datasets were searched using MaxQuant against the Homo sapiens Uniprot Fasta database. Statistical analyses were performed using Mann-Whitney, Kruskal-Wallis and Spearman correlation with p-value Results We identified a total of 3565 proteins secreted by human gut with 29% (1045 proteins) of the proteins, exclusively expressed in CRC and 64.4% (2296 proteins) in non-CRC. Intriguingly, out of the 1045 CRC-associated proteins, we found 12 gender-specific proteins that were significantly secreted in the female patients (p Conclusions Proteins identified in this secretome study of CRC-stricken gut have been previously associated with CRC carcinogenesis and were reported in tissues and serum samples. We are the first group to report such proteins as being secreted by human gut and detectable in the stool. Taken together, these proteins could be viewed as a promising biomarker for CRC diagnosis or prognosis.