IBBL works in close collaboration with national players to support research across a variety of areas, from Parkinson’s Disease (under the National Centre for Excellence in Research in Parkinson’s Disease) to personalised medicine (through the Personalised Medicine Consortium of Luxembourg) and cancer (under the National Cancer Plan). An instance of successful cooperation is the SOCS (Suppressor Of Cytokine Signaling) project which saw the discovery of the protein MYO5B as a colorectal cancer biomarker in 2017.

“We are delighted that the sample collection set up at the national level has been put to the service of Luxembourgish researchers to feed additional colorectal cancer studies. It is exactly what it was intended for!”

Christelle Bahlawane

PhD, Project Manager

A winning partnership…made in Luxembourg

The concerted action against colorectal cancer (CRC) in the Grand Duchy started back in 2011 when researchers from the University of Luxembourg, clinicians and IBBL launched the SOCS (Suppressor Of Cytokine Signaling) study, supported by the Fondation Cancer. Led by Prof. Serge Haan and Dr. Elisabeth Letellier from the Life Sciences Research Unit at the University of Luxembourg, the SOCS study revealed that two members of the SOCS family of proteins*, namely SOCS2 and SOCS6, can serve as diagnostic biomarkers to help the early-stage diagnosis of CRC. Since then, the vast sample collection created under SOCS has given life to a variety of new projects in collaboration with researchers from the Luxembourg Institute of Health (LIH) and the Luxembourg Centre for Systems Biomedicine (LCSB), in a joint effort to further elucidate the mechanisms of CRC and its links to diet and environmental factors such as pesticides. In 2017, the National Health Laboratory (LNS) also joined the SOCS study team, further reinforcing the national collaborative efforts and providing increased opportunities to collect samples from local hospitals.

Three cheers for Luxembourgish research

In 2017, the SOCS project yielded a remarkable result. Based on the collection of tumor samples originating from several Luxembourgish hospitals, such as the Centre Hospitalier Emile Mayrisch (CHEM) and the Centre Hospitalier de Luxembourg (CHL), Prof. Haan and Dr. Elisabeth Letellier identified a new prognostic CRC marker, bringing the number of discovered CRC biomarkers to three. Namely, protein MYO5B of the Myosin V family – a group of proteins involved in cell trafficking and polarisation – was found to have a high potential for the identification of a patient’s risk of relapse. The team used a previously conducted meta-analysis of publicly available gene expression data to analyse the expression of different members of the Myosin V family, specifically MYO5A, 5B, and 5C, in CRC. Subsequently, an independent study was also performed on the Luxembourgish patient cohort. Together, the two studies revealed that the expression and, consequently, the concentration of MYO5B decreases as the disease progresses. Specifically, CRC patients with low MYO5B expression were found to report a weaker chance of survival. “The prognostic ability of MYO5B is especially valuable in the early stages of CRC, helping clinicians match patients with the most effective and appropriate treatment options”, explains Prof. Haan. “The strength of the study lies in the joint effort of an interdisciplinary team of partners, involving bioinformatics and state-of-the-art experimental techniques. Our discovery further consolidates Luxembourg’s reputation as a centre of excellence in cancer and biomedical research in general”, adds Dr. Letellier, principle investigator of the study. The research team is currently in the process of applying for funding for a proof of concept to validate the new MYO5B prognostic biomarker, together with IBBL, and bring it to market. The validation will be the object of the dedicated MyoRPROG project.

A coveted collection

IBBL played an important role in the SOCS project. Working in close cooperation with the other partners, IBBL contributed to establishing an independent cohort of CRC patients. It oversaw all the steps involved in the collection of tumour samples from various Luxembourgish hospitals – 75% of which originating specifically from the CHEM – as well as the storage and redistribution of the specimens and associated medical data. The collection subsequently allowed the researchers from the University of Luxembourg and IBBL to reconfirm the initial results. The collection is of very high value looking ahead, as it sets the foundations for the other research projects on CRC and for the identification of new prognostic biomarkers. “The quality of the samples is the key factor, particularly for this type of research, where the outcome depends on the accuracy of the measurements of very small molecular variations between healthy and malignant tissues”, explains Dr. Christelle Bahlawane, IBBL project manager in charge of SOCS and MyoRPROG. “We are delighted that the SOCS collection has been put to the service of Luxembourgish researchers to feed additional CRC studies. It is exactly what it was intended for!”. Indeed, the collection will be used for the future validation of the novel MYO5B biomarker under the MyoRPROG project.

“Ultimately, the goal is to develop a test that can one day be used clinically”

Monica Marchese

PhD, Biomarker Validation Scientist

The road to biomarker validation

The SOCS project illustrates an important concept. The discovery of a biomarker alone does not guarantee its use in a clinical setting, and therefore needs to be supported by a rigorous validation process. This is where IBBL adds value to studies such as MyoRPROG. “By carrying out all the steps of early validation for its partners and clients, IBBL helps assess the robustness of the biomarker, its precision, specificity, sensitivity and stability”, explains Dr. Monica Marchese, Biomarker Validation Scientist at IBBL. Clinical verification – a pilot study on a small sample size to evaluate the performance of the biomarker in a clinical setting – is also performed. “Ultimately, the goal is to develop a test that can one day be used clinically”, she adds. In the case of the MyoRPROG project, such a test could be based on the combined expression of the MYO5B gene and of another CRC-related gene (RAB8A). This could assist oncologists in their post-surgical decision about the need for chemotherapy in early stages of colorectal cancer, as well as in the follow-up of high-risk patients.

*SOCS proteins have been recognised for their tumor-suppressor and anti-inflammatory functions