Your browser doesn't support javascript.
loading
SMAD4 and NF1 mutations as potential biomarkers for poor prognosis to cetuximab-based therapy in Chinese metastatic colorectal cancer patients.
Mei, Zhu; Shao, Yang W; Lin, Peinan; Cai, Xiaomin; Wang, Biao; Ding, Yan; Ma, Xiangyuan; Wu, Xue; Xia, Yewei; Zhu, Dongqin; Shu, Yongqian; Fu, Zan; Gu, Yanhong.
Afiliación
  • Mei Z; Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
  • Shao YW; Department of Oncology, The Affiliated Sir Run Run Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
  • Lin P; Translational Medicine Research Institute, Geneseeq Technology Inc., Toronto, ON, Canada.
  • Cai X; School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
  • Wang B; Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
  • Ding Y; Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
  • Ma X; Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
  • Wu X; Translational Medicine Research Institute, Geneseeq Technology Inc., Toronto, ON, Canada.
  • Xia Y; Translational Medicine Research Institute, Geneseeq Technology Inc., Toronto, ON, Canada.
  • Zhu D; Translational Medicine Research Institute, Geneseeq Technology Inc., Toronto, ON, Canada.
  • Shu Y; Medical Department, Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, China.
  • Fu Z; Medical Department, Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, China.
  • Gu Y; Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China. shuyongqian1999@126.com.
BMC Cancer ; 18(1): 479, 2018 04 27.
Article en En | MEDLINE | ID: mdl-29703253
BACKGROUND: Cetuximab, an anti-EGFR monoclonal antibody, is used in combination with chemotherapy in clinic to enhance the outcome in metastatic colorectal cancer (mCRC) patients with only ~ 20% response rate. To date only activating mutations in KRAS and NRAS have been identified as poor prognosis biomarkers in cetuximab-based treatment, which makes an urgent need for identification of novel prognosis biomarkers to precisely predict patients' response in order to maximize the benefit. METHODS: In this study, we analysed the mutation profiles of 33 Chinese mCRC patients using comprehensive next-generation sequencing (NGS) targeting 416 cancer-relevant genes before cetuximab treatment. Upon receiving cetuximab-based therapy, patients were evaluated for drug response, and the progression-free survival (PFS) was monitored. The association of specific genetic alterations and cetuximab efficacy was analyzed. RESULTS: Patients carrying SMAD4 mutations (SMAD4mut, n = 8) or NF1 mutations (NF1mut, n = 4) had significantly shorter PFS comparing to those carrying wildtype SMAD4 (SMAD4wt, n = 25) (P = 0.0081) or wildtype NF1 (NF1wt, n = 29) (P = 0.0028), respectively. None of the SMAD4mut or NF1mut patients showed response to cetuximab when assessed at 12-week post-treatment. Interestingly, two patients carrying both SMAD4mut and NF1mut showed the shortest PFS among all the patients. CONCLUSIONS: Our results demonstrated that SMAD4 and NF1 mutations can serve as potential biomarkers for poor prognosis to cetuximab-based therapy in Chinese mCRC patients.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Neurofibromina 1 / Proteína Smad4 / Mutación Tipo de estudio: Prognostic_studies Límite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: BMC Cancer Asunto de la revista: NEOPLASIAS Año: 2018 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Neurofibromina 1 / Proteína Smad4 / Mutación Tipo de estudio: Prognostic_studies Límite: Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: BMC Cancer Asunto de la revista: NEOPLASIAS Año: 2018 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido