Potentially powerful cancer biomarker identified

Protein expression may predict risk of colorectal cancer recurrence

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LUXEMBOURG CITY—A research team at the University of Luxembourg has identified a new biomarker for colorectal cancer (CRC), which holds the potential to help identify patients at greatest risk for recurrence of the disease. This vital piece of information could significantly improve physicians’ ability to choose best-fitting treatment plans for patients based on their recurrence risk profile, in the hopes of ultimately improving therapy and survival rates of patients.
An interdisciplinary research team from the Molecular Disease Mechanisms group at the Life Sciences Research Unit of the University of Luxembourg assembled by Prof. Serge Haan and Dr. Elisabeth Letellier began using a previously established meta-analysis of publicly available gene expression data to identify the protein family myosin—recently reported to be associated with several types of cancer—as a potentially significant marker related to CRC. Further, the meta-analysis combined with an independent patient cohort study revealed the expression of a protein within the myosin family, MYO5B, to be closely linked to the disease, finding that the concentration of the protein decreases as the disease progresses. CRC patients with low MYO5B expression had significantly lower chances of disease- and metastasis-free survival.
Letellier says that although the research team hypothesized that some myosin family members might be dysregulated during carcinogenesis, they were nonetheless surprised by the MYO5B link uncovered in their findings, since previous studies related to cancer have carefully studied other myosin members.
“This study now suggests for the first time the use of MYO5B alone or in combination with its adapter protein RAB8A as a prognostic marker in CRC,” she notes.
The group identified MYO5B as a powerful prognostic biomarker especially in CRC’s early stages (I and II). Early detection and classification are especially important in CRC because not all stage II patients benefit from chemotherapy. Identifying patients at risk for recurrence during the early stages of the disease can inform clinicians’ recommendations for treatment plans and may spare patients from the side effects of unnecessary chemotherapy.
“MYO5B allows delineating a high-risk population in early CRC stages,” says Letellier. “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.”
In the group’s data on MYO5B protein levels, roughly 30 percent of early-stage CRC patients showed a high expression of the protein, suggesting a lower risk of disease recurrence.
“Thirty percent of stage I-II patients identified here represent CRC patients that have a good prognostic value for which chemotherapy would not be necessary,” Letellier explains. “These values will be further refined in follow-up studies.”
The team plans to continue its work to assess the validity of its biomarker in different conditions and in additional patient cohorts.
“The development of a clinical test requires the determination of the parameters that allow a robust and sensitive detection of the biomarkers,” Letellier tells DDNews. “For a potential translation into the clinics, we further need to seek partners from the private sector who would be interested to incorporate our biomarkers into clinical tests. We plan to perform a proof-of-concept study in order to address these issues and bring our biomarker one step further on the way to the clinics.”
According to Letellier, she and Haan set up the colorectal cancer collection in 2009 in collaboration with the Integrated Biobank of Luxembourg, Laboratoire National de la Santé, Clinical and Epidemiological Investigation Center and several hospitals, especially the CHEM (Centre Hospitalier Emile Mayrisch). For this study, the interdisciplinary team consisted of researchers with complementary areas of expertise, including data collection, surgical oncology, pathology, biobanking, bioinformatics and cell biology.
“The expertise of each contributing group was essential for the successful completion of the project,” says Letellier.

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