miROMeS · miRNA biomarkers of Osseous Metastases in Serum from breast cancer patients
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2015-06-01 → 2017-09-20
- EU contribution
- €185,076
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
miRNA biomarkers of Osseous Metastases in Serum from breast cancer patients
Breast cancer is increasingly viewed as manageable for many years since patient survival rates have steadily increased, in which 82-88% of patients are expected to be alive after 5 years. However, bone metastasis is a common complication for breast cancer patients, the rate of bone metastasis still affecting over 70% of advanced-stage patients. This is a complicating factor for patient care, as patients may subsequently develop osteolytic fractures or spinal compression, leading to chronic pain. By the time breast cancer bone metastasis is diagnosed, the disease is considered incurable. Therefore it is a necessity to evaluate the predictive value of candidate biomarkers for bone metastasis in breast cancer patients to improve the detection of high-risk patients. Assessing biomarker prognosis value will also permit to adapt treatment for patients at risk of developing bone metastasis by given preventative treatments such as adjuvant bisphosphonates and/or new preventive therapies. This research emphasizes the importance of health and wellbeing where patient quality of life and patient relapse remains a challenge. Identification of patients at risk of bone metastasis development may lead to decreased drug burden, reducing bone-metastasis related fractures and the need for surgery, providing relief to the health care system. Further, in light of increased breast cancer survival, long-term disease management becomes an alternate health objective. Circulating breast tumor cells that escape the primary tumor and invade the bone marrow express sets of deregulated genes and microRNAs (miRNAs) that facilitate their bone tropism and enhance engraftment of disseminated tumor cell in bone marrow which may subsequently induce osteolytic lesions. Indeed, transcriptional profiling of primary tumors has revealed gene and miRNA signatures that correlate with metastatic bone relapse in patients. Insight into the molecular mechanisms of cancer cell dissemination to bone has been obtained through associations between miRNA expression in primary tumor and metastasis with the involvement of specifically cognate genes during bone metastasis formation. MiRNAs are short and single-stranded RNAs that repress gene expression and that have been suggested as biomarkers of bone disease, driven by their remarkable stability and accessibility in blood and by the property of circulating miRNAs as a reflect of tumor miRNAs. In this, the utility of miRNAs as biomarkers of bone disease has been studied in the present research that has combined the expertise from the ERS in miRNA biomarker analysis and the host laboratory’s expertise in bone metastasis for the following objectives: (i)- To identify genes and miRNAs in breast primary tumors the deregulation of which is associated to bone metastasis occurrence. (ii)- To identify serum miRNA signatures of bone metastasis in breast cancer patients with bone metastasis compared to patients without bone metastasis. (iii)- To evaluate the predictive value of candidate miRNA biomarkers in a focused miRNA panel using serum from patients with long-term follow-up data
Data: CORDIS, © European Union
Project objective
Bone metastasis is a common complication for breast cancer patients, affecting 70% of patients diagnosed at advanced stages. Blood-based microRNAs (miRNAs) have received considerable research interest as biomarkers in cancer. The identification of biomarkers predictive of bone metastasis may be useful for the administration of preventative drugs such as bisphosphonates. In this study, a large-scale screening analysis of > 700 miRNAs will be performed in serum from breast cancer patients with and without visceral or bone metastasis. We will further evaluate candidate miRNAs using serum samples from a second cohort of breast cancer patients who were examined prospectively (with 8 years of follow-up) for relapses in bone and non-bone sites. At this stage, we anticipate the identification of a miRNA signature predictive of bone metastasis in patients with early-stage breast cancer. The second part of this study will assess the role of these miRNAs in the tumour-bone microenvironment. Circulating miRNAs may derive from bone cells or the tumour, and may enter the circulation through cell-derived vesicles called exosomes. We will study the biological functions of miRNAs dysregulated in patient serum. Overlaps between miRNAs in the serum and exosomal miRNAs that are derived from tumour cells or osteoclasts will be further assessed using in vitro and in vivo models of bone metastasis. By studying the activities of these exosomal miRNAs in the bone microenvironment, we may be able to better understand bone metastasis as well as identify new miRNA-based therapeutic targets.
Original text from CORDIS.
Participants
- UNIVERSITE LYON 1 CLAUDE BERNARD · Villeurbanne CedexCoordinatorFrance
Links
Data: CORDIS, © European Union
