Oliver M Fisher1,2,3, Angelique J Levert-Mignon1, Christopher W Lehane1, Natalia K Botelho1, Jesper L V Maag2,4, Melissa L Thomas1, Melanie Edwards5, Sarah J Lord1,6,3, Yuri V Bobryshev1, David C Whiteman7, Reginald V Lord8,9. 1. Gastroesophageal Cancer Program, St. Vincent's Centre for Applied Medical Research, Sydney, Australia. 2. School of Medical Sciences, UNSW Australia, Sydney, Australia. 3. Department of Surgery, School of Medicine, University of Notre Dame, Sydney, Australia. 4. Genomics & Epigenetics Division, Garvan Institute of Medical Research, Sydney, Australia. 5. Douglass Hanley Moir Pathology, Sydney, Australia. 6. NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia. 7. QIMR Berghofer Medical Research Institute, Brisbane, Australia. 8. Gastroesophageal Cancer Program, St. Vincent's Centre for Applied Medical Research, Sydney, Australia. rvlord@stvincents.com.au. 9. Department of Surgery, School of Medicine, University of Notre Dame, Sydney, Australia. rvlord@stvincents.com.au.
Abstract
BACKGROUND: Esophageal and gastroesophageal junctional (GEJ) adenocarcinoma is one of the most fatal cancers and has the fastest rising incidence rate of all cancers. Identification of biomarkers is needed to tailor treatments to each patient's tumor biology and prognosis. METHODS: Gene expression profiling was performed in a test cohort of 80 chemoradiotherapy (CRTx)-naïve patients with external validation in a separate cohort of 62 CRTx-naïve patients and 169 patients with advanced-stage disease treated with CRTx. RESULTS: As a novel prognostic biomarker after external validation, CD151 showed promise. Patients exhibiting high levels of CD151 (≥median) had a longer median overall survival than patients with low CD151 tumor levels (median not reached vs. 30.9 months; p = 0.01). This effect persisted in a multivariable Cox-regression model with adjustment for tumor stage [adjusted hazard ratio (aHR), 0.33; 95 % confidence interval (CI), 0.14-0.78; p = 0.01] and was further corroborated through immunohistochemical analysis (aHR, 0.22; 95 % CI, 0.08-0.59; p = 0.003). This effect was not found in the separate cohort of CRTx-exposed patients. CONCLUSION: Tumoral expression levels of CD151 may provide independent prognostic information not gained by conventional staging of patients with esophageal and GEJ adenocarcinoma treated by esophagectomy alone.
BACKGROUND: Esophageal and gastroesophageal junctional (GEJ) adenocarcinoma is one of the most fatal cancers and has the fastest rising incidence rate of all cancers. Identification of biomarkers is needed to tailor treatments to each patient's tumor biology and prognosis. METHODS: Gene expression profiling was performed in a test cohort of 80 chemoradiotherapy (CRTx)-naïve patients with external validation in a separate cohort of 62 CRTx-naïve patients and 169 patients with advanced-stage disease treated with CRTx. RESULTS: As a novel prognostic biomarker after external validation, CD151 showed promise. Patients exhibiting high levels of CD151 (≥median) had a longer median overall survival than patients with low CD151tumor levels (median not reached vs. 30.9 months; p = 0.01). This effect persisted in a multivariable Cox-regression model with adjustment for tumor stage [adjusted hazard ratio (aHR), 0.33; 95 % confidence interval (CI), 0.14-0.78; p = 0.01] and was further corroborated through immunohistochemical analysis (aHR, 0.22; 95 % CI, 0.08-0.59; p = 0.003). This effect was not found in the separate cohort of CRTx-exposed patients. CONCLUSION: Tumoral expression levels of CD151 may provide independent prognostic information not gained by conventional staging of patients with esophageal and GEJ adenocarcinoma treated by esophagectomy alone.
Authors: Aafke Creemers; Eva A Ebbing; Thomas C Pelgrim; Sjoerd M Lagarde; Faridi S van Etten-Jamaludin; Mark I van Berge Henegouwen; Maarten C C M Hulshof; Kausilia K Krishnadath; Sybren L Meijer; Maarten F Bijlsma; Martijn G H van Oijen; Hanneke W M van Laarhoven Journal: Sci Rep Date: 2018-09-05 Impact factor: 4.379