Study of RNA and Heat Shock Protein (HSP) Derived Biomarkers in Radiation-induced Fibrosis in Patients Treated for Breast Cancer.
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Breast Carcinoma
- Sponsor
- Institut de Cancérologie de Lorraine
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Global mRNA alternative splicing and expression of non-coding RNAs profiles in healthy dermal fibroblasts
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
The purpose of this study is to seeking a molecular signature of pathological radiation induced fibrosis based on the response of skin fibroblasts after irradiation, comparing two groups of patients distinguished by their individual radiosensitivity. The signature will integrate recent insights in terms of alternative splicing of mRNAs and level of expression of non-coding RNAs, particularly long non-coding RNAs, snRNAs, snoRNAs and microRNAs. In each group each expression patterns of candidate HSP proteins potentially predictive of pathological radiation induced fibrosis (HSP27, HSP70, αβ crystalline) in the serum and on cell culture will be characterized.
Investigators
Eligibility Criteria
Inclusion Criteria
- •age ≥ 18 and \<70 years old
- •non metastatic disease
- •ECOG performance status 0 or 1
- •chest size ≤ 110 cm et bra size \<D
- •absence of reconstructive breast surgery
- •patient able to undergo blood samples (haematological conditions allowing blood sample)
- •non-evolving carcinological disease
- •absence of systemic inflammatory disease (other than scleroderma) or diabetes
- •no inflammatory ou infectious flare on biopsy site at the time of inclusion
- •invasive or in situ breast carcinoma
Exclusion Criteria
- •age \<18 or \> 70 years old
- •evolutive cancer / metastatic disease
- •chest size \> 110 cm et bra size ≥ D
- •previous reconstructive breast surgery
- •ECOG performance status \> 1
- •systemic inflammatory disease or diabetes
- •inflammatory ou infectious flare on biopsy site at the time of inclusion, very significant ulceration in the treated breast
- •anemic patients
- •use of oral anticoagulants
- •pregnant or likely to be in 6 months
Outcomes
Primary Outcomes
Global mRNA alternative splicing and expression of non-coding RNAs profiles in healthy dermal fibroblasts
Time Frame: 6 months
frequency of inclusion of individual exons within the set of mRNA isoforms (overall splicing profile) and variation in expression of non-coding RNAs
Secondary Outcomes
- Transcriptomic signature of pathological induced fibrosis when comparing the primary outcome between the two populations on cultured fibroblasts(6 months)
- Transcriptomic signature of pathological induced fibrosis when comparing the primary outcome between the two populations on serum(6 months)
- Individual radiosensitivity on healthy dermal fibroblasts(6 months)
- Comparison of the overall mRNA splicing and non-coding RNA expression profiles between non irradiated and irradiated dermal fibroblasts in the same individual(6 months)
- Changes in cellular distribution of the main non-coding RNAs whose expression varies significantly within the pre-identified signature between the 2 groups of patients(6 months)
- seric HSP proteins potentially predictive of pathological induced fibrosis(6 months)
- Cellular distribution of specific HSP on fibroblast culture in each group of patients(6 months)
- Potential interactions between DNA damage response proteins and candidate HSP(6 months)