Nanostring-based multigene assay to predict recurrence for gastric cancer patients after surgery

PLoS One. 2014 Mar 5;9(3):e90133. doi: 10.1371/journal.pone.0090133. eCollection 2014.

Abstract

Despite the benefits from adjuvant chemotherapy or chemoradiotherapy, approximately one-third of stage II gastric cancer (GC) patients developed recurrences. The aim of this study was to develop and validate a prognostic algorithm for gastric cancer (GCPS) that can robustly identify high-risk group for recurrence among stage II patients. A multi-step gene expression profiling study was conducted. First, a microarray gene expression profiling of archived paraffin-embedded tumor blocks was used to identify candidate prognostic genes (N=432). Second, a focused gene expression assay including prognostic genes was used to develop a robust clinical assay (GCPS) in stage II patients from the same cohort (N=186). Third, a predefined cut off for the GCPS was validated using an independent stage II cohort (N=216). The GCPS was validated in another set with stage II GC who underwent surgery without adjuvant treatment (N=300). GCPS was developed by summing the product of Cox regression coefficients and normalized expression levels of 8 genes (LAMP5, CDC25B, CDK1, CLIP4, LTB4R2, MATN3, NOX4, TFDP1). A prospectively defined cut-point for GCPS classified 22.7% of validation cohort treated with chemoradiotherapy (N=216) as high-risk group with 5-year recurrence rate of 58.6% compared to 85.4% in the low risk group (hazard ratio for recurrence=3.16, p=0.00004). GCPS also identified high-risk group among stage II patients treated with surgery only (hazard ratio=1.77, p=0.0053).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / surgery
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Chemoradiotherapy, Adjuvant
  • Disease-Free Survival
  • Gene Expression Profiling*
  • Humans
  • Kaplan-Meier Estimate
  • Lysosome-Associated Membrane Glycoproteins / genetics
  • Lysosome-Associated Membrane Glycoproteins / metabolism
  • Matrilin Proteins / genetics
  • Matrilin Proteins / metabolism
  • Membrane Proteins
  • NADPH Oxidase 4
  • NADPH Oxidases / genetics
  • NADPH Oxidases / metabolism
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / metabolism*
  • Neoplasm Recurrence, Local / prevention & control
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • Proportional Hazards Models
  • Risk
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / surgery
  • Transcriptome

Substances

  • Biomarkers, Tumor
  • CLIP4 protein, human
  • Carrier Proteins
  • LAMP5 protein, human
  • Lysosome-Associated Membrane Glycoproteins
  • MATN3 protein, human
  • Matrilin Proteins
  • Membrane Proteins
  • NADPH Oxidase 4
  • NADPH Oxidases
  • NOX4 protein, human

Grant support

This study was supported by an Intramural grant from the Samsung Medical Center. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.