Investigators found a methylation-independent loss of MYO5B expression in CRC that matched disease progression, which indicates that the use of MYO5B alone or in combination with its adapter protein RAB8A is a prognostic marker for the disease.
It may now be possible to better stratify patients with stage I and II colorectal cancer (CRC). Researchers from the University of Luxembourg are reporting that they have identified a new biomarker for CRC that may improve staging and subsequently help lower morbidity and mortality.
Determining which CRC patients need the most aggressive treatments has been limited by a lack of prognostic markers. However, proteins from the Myosin family have been recently linked with several types of cancer. Investigators examined a previously established meta-analysis of publicly available gene expression data to try to sort out the expression of different members of the Myosin V family. The team analyzed MYO5A, 5B, and 5C in CRC.
The investigators used laser-microdissected material as well as tissue microarrays from paired human CRC samples. In addition, they validated RNA and protein expression of MYO5B and its known adapter proteins (RAB8A and RAB25) in an independent patient cohort. Principal investigator Elisabeth Letellier, MD, who is with the Molecular Disease Mechanisms group at the Life Sciences Research Unit of the University of Luxembourg, said the group identified myosinVb (MYO5B) as a new diagnostic and a promising prognostic marker for CRC.
“As loss of epithelial architecture and cell differentiation/polarity are intimately linked to cancer, we hypothesized that some Myosin 5 family members, known to be involved in cellular trafficking and polarization of cells, might be dysregulated during carcinogenesis. We were, however, surprised by our findings as previous studies related to cancer have majorly studied other myosin members,” Dr. Letellier told Cancer Network.
She said the current study is the first to suggest that the use of MYO5B alone or in combination with its adapter protein RAB8A is a prognostic marker in CRC. The investigators found that the meta-analysis and the independent patient cohort study showed a methylation-independent loss of MYO5B expression in CRC that matched disease progression.
The data suggest that MYO5B may be especially beneficial in helping stratify patients with stage II disease for adjuvant chemotherapy. “MYO5B allows for delineating a high-risk population in early CRC stages. This stratification could potentially help oncologists to choose the best treatment plan, especially for stage II patients, where adjuvant chemotherapy may not always lead to beneficial results but still results in significant side effects,” said Dr. Letellier.
These new findings could lead to new classifications allowing some CRC patients to be labeled “high-” or “low-” risk. Dr. Letellier said the strength of these study findings can be attributed to their interdisciplinary approaches, which combined bioinformatics and state-of-the-art experimental techniques.