Journal Article

Nanostring-Based Multigene Assay to Predict Recurrence for Gastric Cancer Patients after Surgery

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

2014

Overview

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).

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adenocarcinoma - genetics / Adenocarcinoma - metabolism / Adenocarcinoma - surgery / Adjuvant chemotherapy / Algorithms / Assaying / Biology / Biomarkers, Tumor - genetics / Biomarkers, Tumor - metabolism / Cancer / Cancer patients / Cancer research / Cancer therapies / Carrier Proteins - genetics / Carrier Proteins - metabolism / Cdc25B phosphatase / Chemoradiotherapy / Chemoradiotherapy, Adjuvant / Chemotherapy / Colorectal cancer / Disease-Free Survival / DNA microarrays / Gastric cancer / Gastroenterology / Gene expression / Gene Expression Profiling / Genes / Genomes / Health risks / Hematology / Humans / Hypotheses / Kaplan-Meier Estimate / Liver cancer / Lysosomal Membrane Proteins - genetics / Lysosomal Membrane Proteins - metabolism / Matrilin Proteins - genetics / Matrilin Proteins - metabolism / Medical prognosis / Medical research / Medicine / Membrane Proteins / NADPH Oxidase 4 / NADPH Oxidases - genetics / NADPH Oxidases - metabolism / Neoplasm Recurrence, Local - genetics / Neoplasm Recurrence, Local - metabolism / Neoplasm Recurrence, Local - prevention & control / NOX4 protein / Oligonucleotide Array Sequence Analysis / Oncology / Paraffin / Pathology / Patients / Physicians / Prognosis / Proportional Hazards Models / Radiation therapy / Recurrence (Disease) / Regression coefficients / Risk / Risk groups / Stem cells / Stomach cancer / Stomach Neoplasms - genetics / Stomach Neoplasms - metabolism / Stomach Neoplasms - surgery / Surgery / Transcriptome / Tumors