Identification of Biomarker Profiles GEP-NEN Patients

Neuroendocrine Tumors

Neuroendocrine Tumors, MALDI-MS, Proteomics, Biomarkers, Tumor, Precision Medicine

Although gastroenteropancreatic neuroendocrine neoplasia (GEP-NEN) were considered for years as rare tumors, their incidences are increasing. Due to their potential of early metastases and their heterogenous response to therapy, these tumors are important clinical entities. A major problem remains the impossibility to adequately predict tumors' response to treatment, precluding an individualized therapy. Further, there is no method to efficiently screen these tumors. Protein based analyses (proteomic analyses) gain in interest as methods to address this problematic. The present study was designed to investigate epidemiologic data of patients with GEP-NEN and to answer following questions using proteomic analysis applied to existing pathology specimens (paraffin-embedded specimens, FFPE): is it possible to explore protein signatures in this type of tumors? Is the response to therapy predictable using specific protein signatures? Is the tumor's tendency to metastasize related to specific protein signatures?

Gastroenteropancreatic neuroendocrine neoplasia (GEP-NEN) were considered for years as rare tumors. In last years however, their incidences are increasing (3,65 / 100.000 / year) \[Lawrence et al., 2011; Friling et al, 2014\]. These tumors are important clinical entities: 1) 40-95% of tumors have metastasized at diagnosis, 2) evidence-based data dealing with the therapeutic strategy and screening are still scarce. A central problem remains the impossibility to adequately predict the response to surgery, chemotherapy, radiochemotherapy, peptid-receptor-based Radiotherapy or biotherapy, precluding an individualized therapy (precision medicine) \[Rinke et al., 2014\]. An actual research topic in these patients is the identification of patient markers allowing an response prediction. Moreover, researchers try to identify tumor markers in patients with unknown primary in order to locate the origin of metastases. Further, identification of tumor specific markers would allow the development of screening strategies in GEP-NEN. Due to the ability of these techniques to describe the biological heterogenity of a tumor, proteomics (protein based analysis methods) are promising in the present problematic \[Bezabeh et al., 2014; Löhr et al., 2006; Pan et al., 2013\]. The present study was designed to investigate epidemiologic data of patients with GEP-NEN and to answer following questions using proteomic analysis (MALDI-MS) applied to existing pathology specimens (paraffin-embedded specimens, FFPE): is it possible to explore protein signatures in this type of tumors? Is the response to therapy predictable using specific protein signatures? Is the tumor's tendency to metastasize related to specific protein signatures? The present investigation explores the GEP-NEN database/register of following institutions: University Hospital Schleswig Holstein, University hospital of Freiburg, Agaplesion Hospital Rotenburg. The pathology specimens of the studied register-population, were identified in the biobank and pathology-institutes of the participating hospitals and investigated using MALDI-MS technique.

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