Article (Scientific journals)
Loss of Myosin Vb in colorectal cancer is a strong prognostic factor for disease recurrence
Letellier, Elisabeth; Schmitz, Martine; Ginolhac, Aurélien et al.
2017In British Journal of Cancer, 117 (11), p. 1689-1701
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Keywords :
MYO5B, colorectal cancer; biomarker; prognostic value
Abstract :
[en] Background: Selecting the most beneficial treatment regimens for colorectal cancer (CRC) patients remains challenging due to a lack of prognostic markers. Members of the Myosin family, proteins recognized to play a major role in trafficking and polarization of cells, have recently been reported to be closely associated with several types of cancer and might thus serve as potential prognostic markers in the context of CRC. Methods: We used a previously established meta-analysis of publicly available gene expression data to analyse the expression of different members of the Myosin V family, namely MYO5A, 5B, and 5C, in CRC. Using laser-microdissected material as well as tissue microarrays from paired human CRC samples, we validated both RNA and protein expression of MYO5B and its known adapter proteins (RAB8A and RAB25) in an independent patient cohort. Finally, we assessed the prognostic value of both MYO5B and its adapter-coupled combinatorial gene expression signatures. Results: The meta-analysis as well as an independent patient cohort study revealed a methylation-independent loss of MYO5B expression in CRC that matched disease progression. Although MYO5B mutations were identified in a small number of patients, these cannot be solely responsible for the common down-regulation observed in CRC patients. Significantly, CRC patients with low MYO5B expression displayed shorter overall, disease- and metastasis-free survival, a trend that was further reinforced when RAB8A expression was also taken into account. Conclusions: Our data identifies MYO5B as a powerful prognostic biomarker in CRC, especially in early stages (stages I and II), which might help stratifying patients with stage II for adjuvant chemotherapy.
Research center :
University of Luxembourg
ULHPC - University of Luxembourg: High Performance Computing
Disciplines :
Oncology
Author, co-author :
Letellier, Elisabeth ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Schmitz, Martine ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Ginolhac, Aurélien  ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Rodriguez, Fabien ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Ullmann, Pit ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Qureshi-Baig, Komal
Frasquilho, Sonia;  Integrated Biobank of Luxembourg
Antunes, Laurent;  Integrated Biobank of Luxembourg
Haan, Serge ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
External co-authors :
no
Language :
English
Title :
Loss of Myosin Vb in colorectal cancer is a strong prognostic factor for disease recurrence
Publication date :
21 November 2017
Journal title :
British Journal of Cancer
ISSN :
1532-1827
Publisher :
Nature Publishing Group, London, United Kingdom
Volume :
117
Issue :
11
Pages :
1689-1701
Peer reviewed :
Peer Reviewed verified by ORBi
Focus Area :
Systems Biomedicine
Name of the research project :
Identification of new biomarkers for colorectal cancer
Funders :
Fonds National de la Recherche - FnRF, Fondation Cancer
Available on ORBilu :
since 15 January 2018

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