Potențiali biomarkeri proteici cu utilitate în diagnosticul colangiocarcinomului intrahepatic
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Potential proteomic signature based biomarker for intrahepatic cholangiocarcinoma diagnosis
Researcher Maria Ilieș, PhD – Project Leader
Prof. Cristina Adela Iuga, PhD – Mentor
246.950,00 RON (2 years)
Intrahepatic cholangiocarcinoma (iCCA) is the second most common subtype of liver cancer, fourth leading cause of cancer related deaths worldwide. Worryingly, 2019 statistics show that iCCA incidence rates are raising faster than for any other cancer. With a dismal 5-year relative survival rate of solely 17%, iCCA has a hopeless prognosis explained by its refractory nature and late diagnosis, hindered by its asymptomatic makeup in the early phase. Currently, iCCA is diagnosed by combining clinical, radiological and nonspecific markers. Even thought surgery is a potentially curative option, only few patients can benefit, recurrence and survival rates being discouraging. As such, iCCA represents a global health problem and considerable efforts need to be made towards improving patients overall survival.
One trustworthy option is its early diagnosis by an accurate follow-up of the precursor lesions. Thus, iCCA could be timely detected and successfully treated. The current gold standard for a conclusive diagnosis of liver malignancies is the tumor biopsy. Dismally, its sensitivity is only 74.6% and in patients with typical imagistic criteria of hepatocellular carcinoma, the histological diagnosis is iCCA in 12.5% of the patients. Yet, biopsy is not indicated in the majority of the cases because of the advanced stage and concomitant risks. As such, there is an urgent medical need for the development of an accurate diagnostic tool for iCCA. One encouraging option for iCCA patients could be a proteomic based biomarker signature, currently in the light of personalized medicine studies.
The major objective of the present project proposal is to explore the serum proteome of iCCA patients in comparison to primary sclerosing cholangitis, chronic hepatitis, liver cirrhosis, hepatocellular carcinoma and healthy controls and to find proteomics based biomarker signatures of iCCA towards clinical utility by employing state of the art mass spectrometry based techniques.
O1. Characterization of the serum proteome of iCCA patients in comparison to primary sclerosing cholangitis, chronic hepatitis, liver cirrhosis, hepatocellular carcinoma and healthy controls by a state of the art paramagnetic bead-based sample preparation method and lable free nanoLC- ion mobility UDMSE mass spectrometry based approach.
O2. Identification of differently abundant protein panels as potential biomarkers among the analyzed groups that could aid diagnosis of iCCA, as well as differential diagnosis between the groups.
O3. Validation of the potential biomarkers by using a complementary approach in an independent cohort of patients.
Maria Ilieș, MPharm, PhD
Department of Proteomics and Metabolomics
Research Center for Advanced Medicine-MedFUTURE
"Iuliu Hatieganu" University of Medicine and Pharmacy Cluj-Napoca