Tao Xu1,2,3, Bojin Su2,3, Peiyu Huang3,4, Weihong Wei1, Yanming Deng5, Vasudha Sehgal3, Donghui Wang2, Jun Jiang1, Guoyi Zhang1, Anfei Li2, Huiling Yang2, Francois X Claret3,6. 1. Department of Radiation Oncology, Cancer Center, First People's Hospital of Foshan, Foshan, P. R., China. 2. Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, P. R., China. 3. Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 4. Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, P. R., China. 5. Department of Medical Oncology, Cancer Center, First People's Hospital of Foshan, Foshan, P. R., China. 6. Experimental Therapeutics Academic Program and Cancer Biology Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA.
Abstract
PURPOSE: In patients with Epstein-Barr virus (EBV) associated nasopharyngeal carcinoma (NPC), intertumor heterogeneity causes interpatient heterogeneity in the risk of distant metastasis. We aimed to identify novel biomarkers of metastasis risk using reverse phase protein array (RPPA) profiling of NPC patients at risk for metastasis and considering plasma EBV DNA load. EXPERIMENTAL DESIGN: A total of 98 patients with NPC with and without metastasis after treatment, matched with respect to clinical parameters, are enrolled. Total protein expression is measured by RPPA, and protein functions are analyzed by pathway bioinformatics. RESULTS: The RPPA analysis revealed a profile of 70 proteins that are differentially expressed in metastatic and nonmetastatic tumors. Plasma EBV DNA load after treatment correlated with protein expression level better than plasma EBV DNA load before treatment did. The biomarkers of NPC metastasis identified by proteomics regulate signaling pathways involved in cell cycle progression, apoptosis, and epithelial-mesenchymal transition. The authors identified 26 biomarkers associated with 5-year distant failure-free survival in univariate analysis; five biomarkers remained significant in multivariate analysis. CONCLUSIONS AND CLINICAL RELEVANCE: A comprehensive RPPA profiling study is warranted to identify novel metastasis-related biomarkers and further examine the activation state of signaling proteins to improve estimation of metastasis risk for patients with EBV-associated NPC.
PURPOSE: In patients with Epstein-Barr virus (EBV) associated nasopharyngeal carcinoma (NPC), intertumor heterogeneity causes interpatient heterogeneity in the risk of distant metastasis. We aimed to identify novel biomarkers of metastasis risk using reverse phase protein array (RPPA) profiling of NPC patients at risk for metastasis and considering plasma EBV DNA load. EXPERIMENTAL DESIGN: A total of 98 patients with NPC with and without metastasis after treatment, matched with respect to clinical parameters, are enrolled. Total protein expression is measured by RPPA, and protein functions are analyzed by pathway bioinformatics. RESULTS: The RPPA analysis revealed a profile of 70 proteins that are differentially expressed in metastatic and nonmetastatic tumors. Plasma EBV DNA load after treatment correlated with protein expression level better than plasma EBV DNA load before treatment did. The biomarkers of NPC metastasis identified by proteomics regulate signaling pathways involved in cell cycle progression, apoptosis, and epithelial-mesenchymal transition. The authors identified 26 biomarkers associated with 5-year distant failure-free survival in univariate analysis; five biomarkers remained significant in multivariate analysis. CONCLUSIONS AND CLINICAL RELEVANCE: A comprehensive RPPA profiling study is warranted to identify novel metastasis-related biomarkers and further examine the activation state of signaling proteins to improve estimation of metastasis risk for patients with EBV-associated NPC.
Authors: Eduardo Netto; Hugo Santos; Luís Carvalho; José Luis Capelo-Martínez; Miguel Rito; José Cabeçadas; Margarida Roldão Journal: Rep Pract Oncol Radiother Date: 2020-07-11
Authors: Bojin Su; Tao Xu; Jeff P Bruce; Kenneth W Yip; Ning Zhang; Zeli Huang; Guoyi Zhang; Fei-Fei Liu; Jiyong Liang; Huiling Yang; François X Claret Journal: Oncol Rep Date: 2018-09-07 Impact factor: 3.906