Differential effect of MMSET mRNA levels on survival to first-line FOLFOX and second-line docetaxel in gastric cancer
Wei, Jia (Clinical Cancer Institute of Nanjing University (Xina))
Costa, Carlota (Institut Dexeus)
Shen, Jie (Clinical Cancer Institute of Nanjing University (Xina))
Yu, Lixia (TClinical Cancer Institute of Nanjing University (Xina))
Sanchez, José Javier (Universidad Autónoma de Madrid. Departamento de Medicina Preventiva y Salud Pública)
Qian, Xiaoping (Clinical Cancer Institute of Nanjing University (Xina))
Sun, Xia (Clinical Cancer Institute of Nanjing University (Xina))
Zou, Zhengyun (Clinical Cancer Institute of Nanjing University (Xina))
Giménez-Capitán, Ana (Institut Dexeus)
Yue, Guidong (Clinical Cancer Institute of Nanjing University (Xina))
Guan, Wenxian (Nanjing University. Department of General Surgery (Xina))
Rosell, Rafael Costa (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Liu, Baorui (Clinical Cancer Institute of Nanjing University (Xina))
Universitat Autònoma de Barcelona

Date:	2014
Abstract:	Breast cancer susceptibility gene 1 (BRCA1) expression differentially affects outcome to platinum- and taxane-based chemotherapy. Mediator of DNA damage checkpoint protein 1 (MDC1), p53-binding protein 1 (53BP1), multiple myeloma SET domain (MMSET) and ubiquitin-conjugating enzyme 9 (UBC9) are involved in DNA repair and could modify the BRCA1 predictive model. Mediator of DNA damage checkpoint protein 1, 53BP1, MMSET and UBC9 mRNA were assessed in gastric tumours from patients in whom BRCA1 levels had previously been determined. In vitro chemosensitivity assay, MMSET levels were higher in docetaxel-sensitive samples. In a separate cohort, survival was longer in those with low MMSET (12. 3 vs 8. 8 months; P =0. 04) or UBC9 (12. 4 vs 8. 8 months; P =0. 01) in patients receiving only folinic acid, fluorouracil (5-FU) and oxaliplatin (FOLFOX). Conversely, among patients receiving second-line docetaxel, longer survival was associated with high MMSET (19. 1 vs 13. 9 months; P =0. 003). Patients with high MMSET and BRCA1 attained a median survival of 36. 6 months, compared with 13. 9 months for those with high BRCA1 and low MMSET (P =0. 003). In the multivariate analyses, low MMSET (hazard ratio (HR), 0. 59; P =0. 04) and low UBC9 (HR, 0. 52; P =0. 01) levels were markers of longer survival to first-line FOLFOX, whereas palliative surgery (HR, 2. 47; P =0. 005), low BRCA1 (HR, 3. 17; P =0. 001) and low MMSET (HR, 2. 52; P =0. 004) levels were markers of shorter survival to second-line docetaxel. Breast cancer susceptibility gene 1, MMSET and UBC9 can be useful for customising chemotherapy in gastric cancer patients.
Note:	Altres ajuts: This work was funded by grants from the National Natural Science Foundation of China (grant no. 81000980, 81220108023, 81370064), Jiangsu Provincial Program of Medical Science (BL2012001) and the distinguished young investigator project of Nanjing (JQX12002)
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra, i la creació d'obres derivades, sempre que no sigui amb finalitats comercials i que es distribueixin sota la mateixa llicència que regula l'obra original. Cal que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Gene expression ; MMSET ; FOLFOX ; Second-line docetaxel ; Gastric cancer
Published in:	British journal of cancer, Vol. 110 (05 2014) , p. 2662-2668, ISSN 1532-1827

DOI: 10.1038/bjc.2014.231
PMID: 24809779

7 p, 627.6 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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