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Projects / Programmes source: ARIS

Development of protein microarray for research on gastric cancer proteome

Research activity

Code Science Field Subfield
1.05.00  Natural sciences and mathematics  Biochemistry and molecular biology   

Code Science Field
P004  Natural sciences and mathematics  Biochemistry, Metabolism 
B200  Biomedical sciences  Cytology, oncology, cancerology 
Keywords
gastric cancer, oncogenesis, protein microarrays, bio-chips, protein markers, oncoproteins, proteome
Evaluation (rules)
source: COBISS
Researchers (8)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  18622  PhD Nataša Debeljak  Biochemistry and molecular biology  Researcher  2007 - 2009  249 
2.  18529  Dubravka Germ    Technical associate  2007 - 2009 
3.  21395  PhD Petra Hudler  Medical sciences  Researcher  2007 - 2009  156 
4.  13839  MSc Robert Juvan  Oncology  Researcher  2007 - 2009  189 
5.  28916  PhD Damjana Kastelic  Biochemistry and molecular biology  Researcher  2008 - 2009  33 
6.  24562  Helena Klavžar  Biochemistry and molecular biology  Technical associate  2007 - 2009 
7.  06135  PhD Radovan Komel  Biochemistry and molecular biology  Head  2007 - 2009  1,054 
8.  01528  PhD Stanislav Repše  Oncology  Researcher  2007 - 2009  309 
Organisations (2)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0312  University Medical Centre Ljubljana  Ljubljana  5057272000  77,806 
2.  0381  University of Ljubljana, Faculty of Medicine  Ljubljana  1627066  48,448 
Abstract
The incidence and mortality of gastric cancer have fallen in most of the developed countries, but nonetheless, it remains a major public health issue as the fourth most common cancer and the second leading cause of cancer death worldwide. Due to the oligosymptomatic course of early gastric disease, most cases are diagnosed in the advanced stages. Our intention is to combine the transcriptome level with the protein expression patterns in gastric tumor cells in order to aid in determination of molecular principles of the disease development. The purpose of this study is to develop a protein onco-chip as a new diagnostic tool for early detection of phenotypic markers of gastric cancer cells and precancerous lesions on the proteomic level based on a on a new technology: IRPS (analysis with surface plasmon resonance). This approach enables analysis of proteins ‘in real time’ with no need for special labelling, and also investigation of protein-protein interactions. In parallel, for finding correlations between gene expression and cellular protein content, as well as to assess experiments with the protein onco-chip, transcriptome of gastric cancer will be studied with low-density DNA microarray constructed on the basis of specific group of markers selected from previous studies. We hope to identify important common biomarkers that could enable better understanding of molecular mechanisms of cancerogenesis as well as be potentially important for cancer diagnosis.
Significance for science
The aim of the project was selection of new protein markers for the different development stages of stomach adenocarcinome and its precancerous lesions, and use of these markers in conjunction with classical markers for the design of a protein onco-chip usable as a diagnostic tool for early detection of differential expression patterns of proteins constituting specific signatures in cancer. Results will provide a better basic insight into molecular mechanisms of cancerogenesis and will allow to define a new set of markers corresponding to normal and pathologic physiological states. Developed protein chip will represent valuable prototype for further development of investigative or commercial diagnostic microarrays. When analysing llama VHH protein sequences we develped a computer algorithm based on the discovery of co-evolution of amino acid residues located on the antibody surface, with certain a.a. residues directly implicated in antigen recognition. This discovery could have a high value in recombinant antibody technology, since we can predict and design antigen recognition site from amino acid sequence of an antibody. Highly specific antibodies and/or their hypervariable single-chain doomains belong to top priority research in molecular oncology, because of the expected usefulness in immunotherapy and cancer treatment as well as in design and development of new accurate diagnostic procedures.
Significance for the country
Proteomic approach for looking for specific markers of oncogenesis is introducing new methodology of the post-genomic science to Slovenian medical research and practice. Better insight into molecular mechanisms of oncogenesis and improved selection of markers corresponding to normal and pathologic physiological states will offer possibilities for more efficient early detection of cancer, prediction and follow-up of the disease, and also better therapeutic approach. The interdisciplinary development of a protein microarray is associating approaches of functional genomics, medical molecular biology, nanotechnology and bioinformatics. The developed bio-chips will allow further improvement of research in molecular oncology and will represent valuable prototypes for commercial diagnostic microarrays. The project is also creating starting positions for creation of spin-offs for the development of new diagnostic and therapeutic tools.
Most important scientific results Annual report 2008, final report, complete report on dLib.si
Most important socioeconomically and culturally relevant results Annual report 2008, final report, complete report on dLib.si
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