An algorithm-based meta-analysis of genome- and proteome-wide data identifies a combination of potential plasma biomarkers for colorectal cancer

Danuta R Gawel,Andreas Matussek,Sandra Lilja,Mikael Benson,Renate Slind Olsen,Xinxiu Li,Huan Zhang,Samuel Schäfer,Margaretha Stenmarker,Eun Jung Lee

doi:10.1038/s41598-019-51999-9

Abstract

Screening programs for colorectal cancer (CRC) often rely on detection of blood in stools, which is unspecific and leads to a large number of colonoscopies of healthy subjects. Painstaking research has led to the identification of a large number of different types of biomarkers, few of which are in general clinical use. Here, we searched for highly accurate combinations of biomarkers by meta-analyses of genome- and proteome-wide data from CRC tumors. We focused on secreted proteins identified by the Human Protein Atlas and used our recently described algorithms to find optimal combinations of proteins. We identified nine proteins, three of which had been previously identified as potential biomarkers for CRC, namely CEACAM5, LCN2 and TRIM28. The remaining proteins were PLOD1, MAD1L1, P4HA1, GNS, C12orf10 and P3H1. We analyzed these proteins in plasma from 80 patients with newly diagnosed CRC and 80 healthy controls. A combination of four of these proteins, TRIM28, PLOD1, CEACAM5 and P4HA1, separated a training set consisting of 90% patients and 90% of the controls with high accuracy, which was verified in a test set consisting of the remaining 10%. Further studies are warranted to test our algorithms and proteins for early CRC diagnosis.

Highlights

Screening programs for colorectal cancer (CRC) often rely on detection of blood in stools, which is unspecific and leads to a large number of colonoscopies of healthy subjects
We propose a strategy for identification of potential protein biomarkers for CRC that can be measured in blood, which is based on meta-analysis of published genome- and proteome- wide analyses of CRC tumor tissues and adjacent tissues (AT)[15,16,17,18]
We preselected proteins that were (a) differentially expressed; (b) upregulated in CRC samples compared to AT samples; and (c) predicted to be secreted by the Human Protein Atlas

Summary

Introduction

Screening programs for colorectal cancer (CRC) often rely on detection of blood in stools, which is unspecific and leads to a large number of colonoscopies of healthy subjects. There is the need for improved and more accurate biomarker for early diagnosis of CRC Several such biomarkers have been proposed, including assays for multiple proteins, microRNAs, DNA methylation, or tumor DNA in blood or stools[6,7,8,9,10,11,12]. In order to identify optimal combinations of a limited number of proteins, we used our recently described classification algorithm[20] We tested those biomarkers in plasma from patients with newly diagnosed CRC and healthy controls

Objectives

Methods

Results

Conclusion