Identification and validation of PGLS as a metabolic target for early screening and prognostic monitoring of gastric cancer.

Abstract

BackgroundGastric cancer is the third leading cause of cancer‐related death in the world. The purpose of the present study is to investigate the expression and prognostic significance of 6‐phosphogluconolactonase (PGLS) in gastric cancer.MethodsThe protein extracted from a panel of four pairs of gastric cancer tissues and adjacent tissues, labeled with iTRAQ (8‐plex) reagents, and followed by LC‐ESI‐MS/MS. The expressions of proteins were further validated by immunohistochemistry analysis. The expression levels of mRNA were analyzed and validated in the Oncomine database. The correlations of PGLS with prognostic outcomes were evaluated with Kaplan‐Meier plotter database.ResultsThe present study found that PGLS was significantly up‐regulated in gastric cancer by using iTRAQ‐based proteomics and immunohistochemistry analysis. The sensitivity of PGLS in gastric cancer was 72.9%. The high expression of PGLS was significantly correlated with TNM staging in gastric cancer (p = 0.02). The overexpression of PGLS predicts worse overall survival (OS) and post‐progression survival (PPS) for gastric cancer (OS, HR = 1.48, p = 2.1e‐05; PPS, HR = 1.35, p = 0.015). Specifically, the high PGLS expression predicts poor OS, PPS in male gastric cancer patients, in patients with lymph node metastasis and in patients with Her‐2 (‐).ConclusionsThese findings suggested that PGLS was aberrantly expressed in gastric cancer and predicts poor overall survival, post‐progression survival for gastric cancer patients. The present study collectively supported that PGLS is an important target for early determining and follow‐up monitoring for gastric cancer.