The carcinogenic mechanism consists in the synergetic action of genetic factors and exposome related factors.
The hormone-depended cancers of breast and prostate continue to represents a major public psa cancer meaning 200 problem, whose evolution and outcome is affected by the exposome. MiRNAs are short sequences of about 21 nucleotides that do not encode proteins.
They regulate the expression of genes. The microRNAs are present in human plasma and tissues, interfering with various endogenous molecular pathways. Presently, there is a gap in the knowledge concerning the association between exposome and cancer risk in the case of breast and prostate cancer in Romania.
Dale's fundraiser for Prostate Cancer UK
The same situation is also present at a global scale. Our project is focused on the identification and integration of exposome related miRNA signature patterns as biomarkers for exposome aggressiveness, to predict the genotoxic risk for healthy individuals and to identify different molecular subtypes for these two hormone-dependent cancers breast and prostate.
Therefore, in the context of precision medicine, we intent to characterize specific risk factors related to hormone dependency, based on the miRNA genomic and transcriptomic background and correlate it with the environmental exposure. We then want to transform this integrated signature in a new panel of markers with diagnostic and prognostic value for personalized guidance.
Project Duration: 30 months Total Funding Requested: The Research Center for Advanced Medicine Medfuture promotes the development and application of new technologies in the field of molecular and functional imaging, proteomics, metabolomics and advanced experimental medicine for personalized therapies, as well as clinical studies for pharmacogenomics and pharmacoproteomics that will provide new concepts and approaches and will generate the necessary database for the design of specific therapies based on the identification of molecular mechanisms and triggers in the alteration of the genome and the achievement of the specific fenome in different pathologies.
Therefore, in the context of precision medicine, we intent to characterize specific risk factors for breast and prostate cancers, based on the miRNAs patterns and psa cancer meaning 200 correlate them with the environmental exposure, in order to transform this integrated signature in a new panel of markers with clinical application.
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Specific objectives: 1. To define a specific miRNAs molecular signature at genomic and transcriptomics level related to exposome exposure in breast and prostate two hormone dependent cancers 2. To identify the determinants of the evaluated exposome markers based on the socio-professional and environmental factors evaluated tobacco and alcohol consumption, dietary habits and other possible sources.
Identification of the specific genotoxic signatures, by correlating the environmental factors with molecular alterations, especially related to hormone dependency.
To explore the complex mechanisms and therapeutic insights by integration of miRNA patterns related with the prostate and breast hormonal features, based on functional studies using in vitro models. To use the specific molecular signature related to exposome exposure for hormone dependent breast and prostate cancers and establish its modulation by the environmental factors in control groups and cancer patients, and its validation as prototype for a possible prediction diagnostic test.
The project novelty is focused on a better understanding of risk factors that are associated with other alterations at genomic and transcriptomics level, particularly in the case of miRNAs and their targeted genes, leading to the identification of risk biomarkers for the predisposition to cancer, but also for diagnosis and prognostic.
Estimated results: By developing psa cancer meaning 200 screening tests for early diagnosis of patients with breast and prostate cancer risk and based on the exposome signature, it is possible to develop an optimal and personalized therapeutic plan.
All the results obtained will translate into improved genomic exposome related counseling and therapeutic interventions in Romania, providing key tools for additionally refining coherent prevention biomarkers and therapeutic schemes for patients during the timeline of cancer treatment and disease trajectory.
The results obtained ceai fiere si rinichi fares the proposed project could help to develop new diagnostic tools and therapeutic models for personalized therapies based on the exposome related miRNAs associated signature for patients with breast and prostate cancers.
This will also have an impact on the economic sector. This would imply the development of a new sector for providing all the reagents and devices for these types of evaluation that incorporate the relevant markers for the exposome related miRNAs that can be commercialized by technological or pharmaceutical companies.
Project results: Phase I In order to have access to information about the patients included in the study and their biological samples, each study participant signed an informed consent by which the informed decision was made.
A total of blood samples were collected and processed. The average age of the patients and the healthy donors was From this group, 97 were men mean age The selected clinical cases did not have significant changes in blood profile, chronic diseases or infectious diseases.
A specific molecular signature could be identified, which would subsequently be validated on a new cohort of patients and would allow new correlations with environmental factors and clinical data.
A first stage of quality control in the case of gene expression analysis is represented by the PCA "principal component analysis" analysis, which shows a clear separation of the normal tissue versus tumor tissue samples, currently in the biobank.
Phase II Five microRNAs were identified in the double positive breast cancer sample group.
The miR cluster miR, miRa, miRb and miRtogether with miR, miR, miRa and miRc showed different expression levels between the triple negative breast cancer versus double positive breast cancer. A panel of five transcripts miRa, miR, miRb, miRb and miR was validated in the new set of plasma samples. The overlap of TCGA and plasma data revealed that miRb, miRc, miR and miRc confirmed the differential expression between the two subtypes of breast cancer in tumor tissue and plasma samples.
Abstract Background The coronavirus disease COVID pandemic outbreak forced cancer care providers to face different challenges in terms of prevention and treatment management due to specific precautions implemented for oncological patients.
MiRb was validated on additional samples of normal tissue and tumor tissue. The expression level of this transcript from the TCGA data was correlated with the lung and bone metastatic genes. However, this needs to be further integrated into a regulatory network that works together with other markers that affect patients' prognosis or response to therapy.
Phase III During this step, the in vitro modulation of the effects of heavy metals was also performed, as an integral part of the exposome on normal breast cells.
We exposed the fR2 cell line to 1 μM of As and Cd for a month and a half. In fluorescence confocal microscopy images, cells showed changes in cytoskeleton architecture and mitochondrial agglomeration. Both elements determine the formation of filopodia in cells and morphological changes.
Cd increases the invasion capacity of fR2 cells and, affects the acquisition of the malignant phenotype of fR2 cells.
List of publications: 1. Genetic alterations in sporadic triple negative breast cancer. Epub Dec 5.