PLoS ONE (Jan 2014)

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

  • Jeeyun Lee,
  • Insuk Sohn,
  • In-Gu Do,
  • Kyoung-Mee Kim,
  • Se Hoon Park,
  • Joon Oh Park,
  • Young Suk Park,
  • Ho Yeong Lim,
  • Tae Sung Sohn,
  • Jae Moon Bae,
  • Min Gew Choi,
  • Do Hoon Lim,
  • Byung Hoon Min,
  • Joon Haeng Lee,
  • Poong Lyul Rhee,
  • Jae J Kim,
  • Dong Il Choi,
  • Iain Beehuat Tan,
  • Kakoli Das,
  • Patrick Tan,
  • Sin Ho Jung,
  • Won Ki Kang,
  • Sung Kim

DOI
https://doi.org/10.1371/journal.pone.0090133
Journal volume & issue
Vol. 9, no. 3
p. e90133

Abstract

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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).