Cancer Genetics, Therapeutics & Ultrastructural Pathology Department
Proteomics and functional genomics of cancer
Project title: Proteomics and functional genomics of cancer.
Funding organization: Cyprus Research Promotion Foundation. (New Infrastructure)
Project duration: May 2013 –June 2015
Cancer is the phenotypic end point of numerous genomic and/or epigenomic alterations that have accumulated within cells and of the interactions of such altered cells with the stromal microenvironment. Although cancer is a highly complex and heterogeneous disease, the advent of DNA microarray and proteomic technologies, provide highly promising tools for dissecting the genetic changes that drive the carcinogenesis pathway. In the proposed project we aim to use tissue proteomics and RNA expression studies combined with quantitative PCR assays, to identify proteins/genes that are important in driving breast and prostate cancer neoplasia. The latter, are two of the commonest types of cancer that affect the Cypriot and European populations. Population screening programs for these two common cancer types are currently taking place in Cyprus. This project is perfectly timed in that it will collaborate with these initiatives, and lead to the establishment of a state of the art research infrastructure that will be used to perform high calibre research in biomarker discovery. Consequently this project will have substantial benefits for the Cypriot and International Cancer community. The infrastructure that will be provided will pave the way for discovering biomarkers, for two of the commonest cancers, affecting humans.
We will apply tissue proteomics to interrogate the proteome of pre-malignant and malignant lesions of both the breast and prostate organs, using state of the art mass spectrometry technologies. Tissue sections and laser capture microdissection (LCM) will be used to isolate homogeneous populations of cells, prior to analyte (DNA, RNA, protein) isolation. Differences in proteomic profiles between benign and malignant tissues will be further investigated at the RNA level in order to identify genes that are uniquely expressed and correlate with disease progression. Differentially expressed proteins/genes that are associated with disease progression and neoplasia will be validated across laboratories and in a larger set of patients, in order to test for the presence of novel biomarkers.
The main aim is to improve our understanding of the molecular mechanisms underlying breast and prostate cancer neoplasia and to develop biomarkers that can benefit patient management and improve their survival and quality of life. It is expected that novel markers will be identified, that will have the potential to be further exploited for developing disease related biomarkers for early diagnosis and prognosis of patients affected with either breast or prostate cancer.
Implementation of the proposed project requires the establishment of a proteomics facility, acronym PROFILE, which will supplement and strengthen the scientific endeavours of CING and Cyprus. In addition it will provide the Cypriot scientific community with a cutting edge state of the art infrastructure, that will increase research capacity and enhance its competitiveness.
The objectives are:
(1) Establishment and organisation of PROFILE.
(2) Identification of markers involved in breast cancer neoplasia.
(3) Identification of markers involved in prostate cancer neoplasia.
(4) Initial validation of biomarkers for screening, early diagnosis and prognosis of breast and prostate cancer patients.
Coordinating centre: The Cyprus Institute of Neurology and Genetics
Co-ordinator: Professor K.Kyriacou
PA1 Hippocrateon Private Hospital
PA2 University of Bradford
PA3 University of Southamptom
PA4 Mount Sinai Hospital