A 4-gene signature from histologically normal surgical margins predicts local recurrence in patients with oral carcinoma: clinical validation

Autor: Ralph W. Gilbert, Dale H. Brown, Rashmi S. Goswami, Patricia P Reis, Suzanne Kamel-Reid, Yali Xuan, Bayardo Perez-Ordonez, Colleen Simpson, David P. Goldstein, Ana L Seneda, Tomas Tokar, Luis E. S. Móz, Jonathan C. Irish, Igor Jurisica, Patrick J. Gullane, Mahadeo A. Sukhai
Přispěvatelé: Universidade Estadual Paulista (Unesp), University Health Network, Sunnybrook Health Sciences Centre, Brazilian Institute for Cancer Control, University of Toronto, Slovak Academy of Sciences, The University of Toronto
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Scopus
Repositório Institucional da UNESP
Universidade Estadual Paulista (UNESP)
instacron:UNESP
Scientific Reports
Scientific Reports, Vol 10, Iss 1, Pp 1-8 (2020)
Popis: Made available in DSpace on 2020-12-12T01:55:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-12-01 Canada Foundation for Innovation Ontario Institute for Cancer Research Canada Research Chairs Prognostic biomarkers for recurrence of Oral Squamous Cell Carcinoma (OSCC) are urgently needed. We aimed to independently validate a 4-gene expression signature (MMP1, COL4A1, P4HA2, THBS2) predictive of OSCC recurrence risk. Gene expression was measured using Nanostring nCounter® in 245 histologically normal surgical resection margins from 62 patients. Association between risk scores for individual patients and recurrence was assessed by Kaplan-Meier analysis. Signature performance was quantified by concordance index (CI), hazard ratio (HR) and the area under receiver operating characteristics (AUC). Risk scores for recurrence were significantly higher than recurrence-free patients (p = 9.58e-7, Welch’s t-test). A solid performance of the 4-gene signature was determined: CI = 0.64, HR = 3.38 (p = 1.4E-4; log-rank test), AUC = 0.71. We showed that three margins per patient are sufficient to preserve predictive performance (CI = 0.65; HR = 2.92; p = 2.94e-3; AUC = 0.71). Association between the predicted risk scores and recurrence was assessed and showed HR = 2.44 (p = 9.6E-3; log-rank test, N = 62). Signature performance analysis was repeated using an optimized threshold (70th percentile of risks), resulting in HR = 3.38 (p = 1.4E-4; log-rank test, N = 62). The 4-gene signature was validated as predictive of recurrence risk in an independent cohort of patients with resected OSCC and histologically negative margins, and is potentially applicable for clinical decision making on adjuvant treatment and disease monitoring. São Paulo State University UNESP Faculty of Medicine Department of Surgery and Orthopedics Krembil Research Institute University Health Network Department of Clinical Pathology Sunnybrook Health Sciences Centre Princess Margaret Cancer Centre University Health Network Brazilian Institute for Cancer Control Department of Pathology Toronto General Hospital University Health Network Departments of Medical Biophysics University of Toronto Department of Computer Science University of Toronto Institute of Neuroimmunology Slovak Academy of Sciences Clinical Laboratory Genetics Genome Diagnostics University Health Network Department of Laboratory Medicine and Pathobiology The University of Toronto São Paulo State University UNESP Faculty of Medicine Department of Surgery and Orthopedics
Databáze: OpenAIRE
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