title: Nanostring-based multigene assay to predict recurrence for gastric cancer patients after surgery.
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).
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Samsung Cancer Research Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Insuk
authors.initials: I
authors.lastname: Sohn
authors.affiliation: Samsung Cancer Research Institute, Samsung Medical Center, Seoul, Korea; Department of Pathology, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: In-Gu
authors.initials: IG
authors.lastname: Do
authors.affiliation: Department of Pathology, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Kyoung-Mee
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Park
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Joon Oh
authors.initials: JO
authors.lastname: Park
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Park
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Ho Yeong
authors.initials: HY
authors.lastname: Lim
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Tae Sung
authors.initials: TS
authors.lastname: Sohn
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jae Moon
authors.initials: JM
authors.lastname: Bae
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Min Gew
authors.initials: MG
authors.lastname: Choi
authors.affiliation: Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Do Hoon
authors.initials: DH
authors.lastname: Lim
authors.affiliation: Department of Gastroenterology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Byung Hoon
authors.initials: BH
authors.lastname: Min
authors.affiliation: Department of Gastroenterology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Joon Haeng
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Gastroenterology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Poong Lyul
authors.initials: PL
authors.lastname: Rhee
authors.affiliation: Department of Gastroenterology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jae J
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Dong Il
authors.initials: DI
authors.lastname: Choi
authors.affiliation: Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School Singapore, Singapore.
authors.forename: Iain Beehuat
authors.initials: IB
authors.lastname: Tan
authors.affiliation: Genome Institute of Singapore, Singapore, Singapore.
authors.forename: Kakoli
authors.initials: K
authors.lastname: Das
authors.affiliation: Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School Singapore, Singapore; Genome Institute of Singapore, Singapore, Singapore; Cancer Science Institute of Singapore, Singapore, Singapore.
authors.forename: Patrick
authors.initials: P
authors.lastname: Tan
authors.affiliation: Samsung Cancer Research Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Sin Ho
authors.initials: SH
authors.lastname: Jung
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Won Ki
authors.initials: WK
authors.lastname: Kang
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sung
authors.initials: S
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D059186:Chemoradiotherapy, Adjuvant; D018572:Disease-Free Survival; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D051907:Lysosomal Membrane Proteins / Q000235:genetics / Q000378:metabolism; D064235:Matrilin Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012306:Risk; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; C489394:CLIP4 protein, human; D002352:Carrier Proteins; C561580:LAMP5 protein, human; D051907:Lysosomal Membrane Proteins; C577545:MATN3 protein, human; D064235:Matrilin Proteins; D008565:Membrane Proteins; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human