Objectives:
to establish the molecular risk of metastatic disease in patients already diagnosed with pancreatic cancer, with prognostic role;
to identify certain biomarkers for detecting early pancreatic cancer;
to stratify the malignancy risk according to the proteomic modifications at the patients with risk factors for pancreatic cancer (chronic pancreatitis, diabetes mellitus);
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| DESCRIPTION | PANGEN is a complex project that has in view the identification of certain molecular biomarkers in the pancreatic cancer. Being a disease with a 5 years survival of less than 5%, it is difficult to detect it precisely by classical diagnosis means. Also it is difficult to make the differential diagnosis with the pseudotumoral chronic pancreatitis, which has similar imagistic and clinical features, so surgery with hystopathologic diagnosis is needed. The preoperative staging of the pancreatic cancer has a limited accuracy (max. 85%), no matter what imagistic method is used. Up to now, no predictive tumor or host features (e.g. immune response) responsible for distant metastasis are known. In practice, the hepatic metastases under 1 cm are often unidentified before surgery through conventional imagistic methods, being detected only during surgery or becoming visible during the immediate postsurgical follow-up. New accurate and cost-efficient diagnosis tools are necessary, with role of predictive biomarker for malignancy in doubtful cases or in patients with risk factors (diabetes, chronic pancreatitis) and useful as a prognostic indicator in cases already diagnosed. Such markers have to be looked for among the tumoral molecular factors involved in tumorigenesis process. The modifications of the human genome, reflected by mutations of proto-oncogenes or tumoral suppression genes have been long researched on the surgical samples or on cell cultures. Thus, there were identified the overexpression of the genes involved in apoptosis (caspasis 1, EGF), the pro-angiogenic factors (VEGF, Il8, angiogenine, VCAM, ICAM, PDGF), the stimulating factors of cell migration (integrine) or the cytokines involved in the immunologic response of the body to the presence of tumors (interleukins, nuclear factor KB, TNF alpha, interferon gamma). Also, through studies of proteomics, proteins over expressed in the malignant pancreatic tissue were selected over the benign ones. Unfortunately, important genetic information regarding the locally advanced or metastatic tumors was lost, tumors considered unfitted for surgery. Therefore, the use of tissular material obtained from these unoperated tumors could emphasize, according to the advanced stage of the disease, the genome and proteic expression modifications, by establishing a genetic algorithm, predictive for metastasis and with prognostic implications. Although the pancreas has a deep location in the abdomen and pancreatic biopsies done by transabdominal procedures are associated with serious risk of fistulas, the pancreatic tissular samples for this proposal will be obtained through a minimum invasive method, endoscopic ultrasonography using fine needle aspiration. The materia resulted, evaluated through the microarray technique and proteomic analysis, will allow a quick analysis of the set of molecular modifications from the pancreatic cancer, comparative with a group of chronic pancreatitis. The tumoral genetic modifications, expressed through the proteic synthesis in the pancreatic tissue, can be found in serum, where from, once identified, they can be considered signals of morbid status of the body. Although plasma or serum is easy to be sampled, the proteic biomarkers are difficult to be identified because their concentration is less than those of dominant proteins with high molecular weight (albumin, globulins). The method proposed for protein assessment in this project, mass spectrometry, allow the identification of the proteins with low molecular mass, hyper expressed in the serum of patients with pancreatic tumors comparatively with a control group. The disappearance or decrease of their concentration after surgical removal of the tumor will represent starting points for the identification of certain biomarkers in early pancreatic cancer. |
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