Abstract

So far, stomach-specific biomarkers, gastric cancer(GC)-related environmental factors, and cancer-associated biomarkers are three major classes of serological biomarkers with GC warning potential, joint detection of which is expected to increase the diagnosis efficiency. We investigated whether the combination of serum pepsinogens(PGs), IgG anti-Helicobacter pylori (HpAb), and osteopontin (OPN) can be used as a panel for GC diagnose. Serum was collected from 365 GC patients and 729 healthy individuals,furtherly 332 cases and 332 age- and sex-matched controls were selected for the matched analysis. Serum levels were measured by ELISA. Logistic regression and receiver operator characteristic curve (ROC) were used to assess the associations of biomarkers with GC and the discriminative performance of biomarkers for GC. The area under ROC from three-dimensional combination of PGI/II-HpAb-OPN (0.826) was significantly higher than two-dimensional combination of PGI/II-HpAb (0.786, P < 0.001), PGI/II-OPN (0.787, P < 0.001), and OPN-HpAb (0.801, P = 0.006), as well as one-biomarker of PGI/II (0.735, P < 0.001), HpAb (0.737, P < 0.001) and OPN(0.713, P < 0.001), respectively. The combination of PGI/II-HpAb-OPN, yielded a sensitivity of 70.2% and specificity of 78.3% at the predicted probability of 0.493 as the optimal cutoff point. Three-dimensional combined biomarkers assay could improve diagnostic accuracy for gastric cancer.

Highlights

  • More accurate biomarkers for prediction of gastric cancer (GC) may contribute for early detection to reduce the mortality

  • Serum levels of PGII, HpAb, and OPN were statistically significantly higher in the GC cases compared with the unmatched controls (P < 0.001) or the matched controls (P < 0.001)

  • The results from the present study suggested that the combination of serum PGI/II, HpAb and OPN had a stronger predictive ability for the presence of GC than any individual biomarker or any combination of two biomarkers did

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Summary

Introduction

More accurate biomarkers for prediction of gastric cancer (GC) may contribute for early detection to reduce the mortality. Available serological biomarkers for GC could be classified into three major categories: stomach-specific biomarkers, GC-related environmental factors and cancer-associated biomarkers, which have been investigated extensively for detecting GC These three types of biomarkers have distinguishing features. Our previous cross-sectional findings that serum anti-H.pylori IgG antibody titer was positively correlated with grade of histological gastritis and mucosal bacterial density[12]. The latter includes those closely related to the occurrence www.nature.com/scientificreports/. We first jointly measured the expression of pepsinogen (PGI, PGII, PGI/PGII ratio), HpAb and OPN in serum, aiming to clarify whether the three-dimensional combined biomarkers assay could improve diagnostic accuracy for gastric cancer

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