Identification of serum proteins AHSG, FGA and APOA-I as diagnostic biomarkers for gastric cancer

Feiyu Shi,Qian Qin,Yingchao Li,Hong Wu,Qingxia Wei,Yaguang Li,Kai Qu,Tianyu Yu,Chengxin Shi,Junjun She,Xin Jin,Xiaofan Xiong,Liang Cheng,Fanni Li,Qi Sun

doi:10.1186/s12014-018-9194-0

Abstract

BackgroundThe development of clinically accessible biomarkers is critical for the early diagnosis of gastric cancer (GC) in patients. High-throughput proteomics techniques could not only effectively generate a serum peptide profile but also provide a new approach to identify potentially diagnostic and prognostic biomarkers for cancer patients.MethodsIn this study, we aim to identify potentially discriminating serum biomarkers for GC. In the discovery cohort, we screened potential biomarkers using magnetic-bead-based purification and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in 64 samples from 32 GC patients that were taken both pre- and post-operatively and 30 healthy volunteers that served as controls. In the validation cohort, the expression patterns and diagnostic values of serum FGA, AHSG and APOA-I were further confirmed by ELISA in 42 paired GC patients (pre- and post-operative samples from 16 patients with pathologic stage I/II and 26 with stage III/IV), 30 colorectal cancer patients, 30 hepatocellular carcinoma patients, and 28 healthy volunteers.ResultsClinProTools software was used and annotated 107 peptides, 12 of which were differentially expressed among three groups (P < 0.0001, fold > 1.5). These 12 peptide peaks were further identified as FGA, AHSG, APOA-I, HBB, TXNRD1, GSPT2 and CAKP5. ELISA data suggested that the serum levels of FGA, AHSG and APOA-I in GC patients were significantly different compared with healthy controls and had favorable diagnostic values for GC patients. Moreover, we found that the serum levels of these three proteins were associated with TNM stages and could reflect tumor burden.ConclusionOur findings suggested that FGA, AHSG and APOA-I might be potential serum biomarkers for GC diagnosis.

Highlights

The development of clinically accessible biomarkers is critical for the early diagnosis of gastric cancer (GC) in patients
The serum samples fractionated by MB-IMAC-Cu and MALDITOF–MS showed that pre-operative GC patients, post-operative GC patients and controls had proteomic profiles that ranged from 1000 to 10,000 Da (Fig. 1c)
Principal component analysis revealed that pre-operative GC patients, postoperative GC patients and control samples could be distinguished by several peptides (Fig. 1d, e), which suggested the possibility of exploring serum biomarkers to separate GC patients from control subjects

Summary

Introduction

The development of clinically accessible biomarkers is critical for the early diagnosis of gastric cancer (GC) in patients. High-throughput proteomics techniques could effectively generate a serum peptide profile and provide a new approach to identify potentially diagnostic and prognostic biomarkers for cancer patients. Gastric cancer (GC) is the fourth most common cancer with almost 1000,000 new cases diagnosed every year [1]. Shi et al Clin Proteom (2018) 15:18 biomarkers were considered the most important biomarkers to reflect tumor burden and have been applied for cancer diagnosis and post-operation monitoring. The conventional serum-based biomarkers for GC, such as carcino-embryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and CA72-4, did not have favorable specificity and sensitivity, which always resulted in delayed diagnosis [7, 8]. Ebert MP et al stated that the sensitivities of above three biomarkers are only 16–63, 20–56, and 18–51%, respectively [9]

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