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

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...

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Main Authors: 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
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0090133&type=printable
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Summary: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).
ISSN:1932-6203