Novel urinary protein biomarker panel for early diagnosis of gastric cancer

Takaya Shimura,Tomonori Yamada,Ayumu Taguchi,Hiroyasu Iwasaki,Samir M Hanash,Tamaki Yamada,Yusuke Okuda,Hong Wang,Mika Kitagawa,Delphine Dayde,Hiromi Kataoka,Masahide Ebi

doi:10.1038/s41416-020-01063-5

Abstract

BackgroundWith the goal of discovering non-invasive biomarkers for early diagnosis of GC, we conducted a case-control study utilising urine samples from individuals with predominantly early GC vs. healthy control (HC).MethodsAmong urine samples from 372 patients, age- and sex-matched 282 patients were randomly divided into three groups: 18 patients in a discovery cohort; 176 patients in a training cohort and 88 patients in a validation cohort.ResultsAmong urinary proteins identified in the comprehensive quantitative proteomics analysis, urinary levels of TFF1 (uTFF1) and ADAM12 (uADAM12) were significantly independent diagnostic biomarkers for GC, in addition to Helicobacter pylori status. A urinary biomarker panel combining uTFF1, uADAM12 and H. pylori significantly distinguished between HC and GC patients in both training and validation cohorts. On the analysis for sex-specific biomarkers, this combination panel demonstrated a good AUC of 0.858 for male GC, whereas another combination panel of uTFF1, uBARD1 and H. pylori also provided a good AUC of 0.893 for female GC. Notably, each panel could distinguish even stage I GC patients from HC patients (AUC = 0.850 for males; AUC = 0.845 for females).ConclusionsNovel urinary protein biomarker panels represent promising non-invasive biomarkers for GC, including early-stage disease.

Highlights

With the goal of discovering non-invasive biomarkers for early diagnosis of Gastric cancer (GC), we conducted a case-control study utilising urine samples from individuals with predominantly early GC vs. healthy control (HC)
+ H.pylori: area under the curve (AUC) = 0.832, 95% confidence interval (CI), 0.773–0.892) (Fig. 2a). These results suggested that a urinary biomarker panel combining urinary levels of trefoil factor 1 (TFF1) (uTFF1), uADAM12 and H. pylori status might provide a good diagnostic biomarker for GC
Receiver operating characteristic (ROC) analysis of a urinary biomarker panel combining uTFF1 and uADAM12 for the validation cohort showed significant differentiation between HC and GC groups

Summary

Introduction

With the goal of discovering non-invasive biomarkers for early diagnosis of GC, we conducted a case-control study utilising urine samples from individuals with predominantly early GC vs. healthy control (HC). A urinary biomarker panel combining uTFF1, uADAM12 and H. pylori significantly distinguished between HC and GC patients in both training and validation cohorts. On the analysis for sex-specific biomarkers, this combination panel demonstrated a good AUC of 0.858 for male GC, whereas another combination panel of uTFF1, uBARD1 and H. pylori provided a good AUC of 0.893 for female GC. Endoscopy with pathological diagnosis from a biopsy sample is currently the gold standard for diagnosing GC but is unsuitable for mass-screening due to the high invasiveness, risk, and financial and time costs. Testing with H. pylori antibody is not recommended for population-based screening due to insufficient evidence. It may offer a good predictor of future GC development, but does not provide a suitable indicator of current GC

Methods

Results

Conclusion