In-Seob Lee1,2, Jiyoung Ahn3, Kwangsoo Kim3, Yoshinaga Okugawa4, Yuji Toiyama4, Hoon Hur5,6, Ajay Goel7,8. 1. Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Monrovia, CA, USA. 2. Department of Surgery, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Korea. 3. Transdisciplinary Department of Medicine and Advanced Technology, Seoul National University Hospital, Seoul, Korea. 4. Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie, Japan. 5. Department of Surgery, Ajou University of School of Medicine, Suwon, Korea. 6. Cancer Biology Graduate Program, Ajou University Graduate School of Medicine, Suwon, Korea. 7. Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Monrovia, CA, USA. ajgoel@coh.org. 8. City of Hope Comprehensive Cancer Centre, Duarte, CA, USA. ajgoel@coh.org.
Abstract
BACKGROUND: Delayed detection of tumours contributes to poor prognosis in patients with gastric cancer (GC). The invasive nature of endoscopy and the absence of an effective serum markers highlight the need to develop novel, noninvasive biomarkers. METHODS: We performed biomarker discovery and validation to identify candidate genes in three gene expression data sets. After validating the gene panel in clinical tissues, we translated the gene panel into serum samples by performing training and validation in 89 samples from GC patients and 54 from healthy donors in two independent cohorts. RESULTS: We identified a nine-gene panel in the discovery phase, with subsequent validation in tissue specimens. Using a serum training cohort, we developed a 5-gene risk prediction formulae for the diagnosis of GC; bootstrapped analysis exhibited an AUC of 0.896. We validated this 5-gene biomarker panel using an independent serum cohort, yielding an AUC of 0.947. This biomarker panel successfully identified GC, regardless of tumour histology. Notably, biomarker performance for detection of stage 1 and 2 GC displayed an AUC of 0.928 and 0.980 in both serum cohorts. CONCLUSIONS: We identified a novel 5-gene biomarker panel for noninvasive diagnosis of GC, which might serve as a potential diagnostic tool for early detection.
BACKGROUND: Delayed detection of tumours contributes to poor prognosis in patients with gastric cancer (GC). The invasive nature of endoscopy and the absence of an effective serum markers highlight the need to develop novel, noninvasive biomarkers. METHODS: We performed biomarker discovery and validation to identify candidate genes in three gene expression data sets. After validating the gene panel in clinical tissues, we translated the gene panel into serum samples by performing training and validation in 89 samples from GC patients and 54 from healthy donors in two independent cohorts. RESULTS: We identified a nine-gene panel in the discovery phase, with subsequent validation in tissue specimens. Using a serum training cohort, we developed a 5-gene risk prediction formulae for the diagnosis of GC; bootstrapped analysis exhibited an AUC of 0.896. We validated this 5-gene biomarker panel using an independent serum cohort, yielding an AUC of 0.947. This biomarker panel successfully identified GC, regardless of tumour histology. Notably, biomarker performance for detection of stage 1 and 2 GC displayed an AUC of 0.928 and 0.980 in both serum cohorts. CONCLUSIONS: We identified a novel 5-gene biomarker panel for noninvasive diagnosis of GC, which might serve as a potential diagnostic tool for early detection.
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