Loss of Myosin Prognostic for Colorectal Cancer Recurrence

Loss of the protein Myosin Vb in colorectal cancer (CRC) patients has been identified as a strong prognostic factor for recurrence of the disease.

Early detection and classification of CRC is of great importance, since not all Stage II patients benefit from chemotherapy. There are few known prognostic markers for CRC so that many patients suffer needlessly from side effects of the chemotherapy without having real benefits. Members of the Myosin family, proteins recognized to have 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.

Myosin V is an unconventional myosin motor, which translocates along actin filaments traveling towards the barbed end of the filaments. Myosin V is involved in the transport of cargo (e.g. RNA, vesicles, organelles, mitochondria) from the center of the cell to the periphery, but has been furthermore shown to act like a dynamic tether, retaining vesicles and organelles in the actin-rich periphery of cells.

Investigators at the University of Luxembourg (Belvaux) used a previously established meta-analysis of publicly available gene expression data to analyze 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, they validated both RNA and protein expression of Myosin Vb (MYO5B) and its known adapter proteins (RAB8A and RAB25) in an independent patient cohort. Finally, they assessed the prognostic value of both MYO5B and its adapter-coupled combinatorial gene expression signatures.

Results revealed methylation-independent loss of MYO5B expression in CRC that matched disease progression. 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. These findings identified MYO5B as a powerful prognostic biomarker in CRC, especially in early stages (stages I and II), which could help stratifying patients with stage II for adjuvant chemotherapy.

"The strength of the study lies in the concerted effort and the interdisciplinary approaches, involving bioinformatics and state-of-the-art experimental techniques. Especially the financial support from the Fondation Cancer has been crucial for the successful completion of our biomarker projects," said senior author Dr. Elisabeth Letellier, research associate in life sciences at the University of Luxemburg.

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