TY - JOUR
T1 - Loss of Myosin Vb in colorectal cancer is a strong prognostic factor for disease recurrence
AU - Letellier, Elisabeth
AU - Schmitz, Martine
AU - Ginolhac, Aurélien
AU - Rodriguez, Fabien
AU - Ullmann, Pit
AU - Qureshi-Baig, Komal
AU - Frasquilho, Sonia
AU - Antunes, Laurent
AU - Haan, Serge
N1 - Funding Information:
We thank the Fondation Cancer for funding this study and the Fonds National de la Recherche (FNR) for its support of KQB and PU under the AFR grant scheme. We are grateful to the Fondation Pélican for its support of KQB and PU. We thank the contributing surgeons, in particular Dr Nikolaus Zügel and Dr Marc Boulmont, from the Centre Hospitalier Emile Mayrisch in Esch-sur-Alzette, and the nurses of the Clinical and Epidemiological Investigation Center of the Luxembourg Institute of Health, for their work with the patients. We thank Dr Nikolai Goncharenko, Dr Christelle Bahlawane, and Dr Fay Betsou from the IBBL for their assistance in establishing a sample collection for the study. Some of the computational work was carried out using the HPC facilities of the University of Luxembourg (Varrette et al, 2014). We thank the Laboratoire national de santé for a second blinded assessment and confirmation of the pathological report. Finally, we thank Martin Nurmik for manuscript corrections.
Publisher Copyright:
© 2017 Cancer Research UK. All rights reserved.
PY - 2017/11/21
Y1 - 2017/11/21
N2 - 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 recognised to have a major role in trafficking and polarisation 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 Myosin Vb (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 downregulation 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 identify 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.
AB - 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 recognised to have a major role in trafficking and polarisation 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 Myosin Vb (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 downregulation 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 identify 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.
KW - MYO5B
KW - RAB8A
KW - biomarker
KW - colorectal cancer
KW - prognostic value
KW - treatment
UR - http://www.scopus.com/inward/record.url?scp=85034822158&partnerID=8YFLogxK
U2 - 10.1038/bjc.2017.352
DO - 10.1038/bjc.2017.352
M3 - Article
C2 - 29024942
AN - SCOPUS:85034822158
SN - 0007-0920
VL - 117
SP - 1689
EP - 1701
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 11
ER -