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    Potential Role of Seven Proteomics Tissue Biomarkers for Diagnosis and Prognosis of Prostate Cancer in Urine
    (MDPI AG, 2022-12-16)
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    Rusevski, Aleksandar
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    Popov, Zivko
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    <jats:p>As the currently available tests for the clinical management of prostate cancer (PCa) are still far from providing precise diagnosis and risk stratification, the identification of new molecular marker(s) remains a pertinent clinical need. Candidate PCa biomarkers from the published proteomic comparative studies of prostate tissue (2002–2020) were collected and systematically evaluated. AZGP1, MDH2, FABP5, ENO1, GSTP1, GSTM2, and EZR were chosen for further evaluation in the urine of 85 PCa patients and controls using ELISA. Statistically significant differences in protein levels between PCa and BPH showed FABP5 (p = 0.019) and ENO1 (p = 0.015). A biomarker panel based on the combination of FABP5, ENO1, and PSA provided the highest accuracy (AUC = 0.795) for PCa detection. The combination of FABP5, EZR, AZGP1, and MDH2 showed AUC = 0.889 in PCa prognosis, with 85.29% of the samples correctly classified into low and high Gleason score (GS) groups. The addition of PSA to the panel slightly increased the AUC to 0.914. AZGP1, FABP5, and EZR showed significant correlation with GS, stage, and percentage of positive biopsy cores. Although validation using larger patient cohorts will be necessary to establish the credibility of the proposed biomarker panels in a clinical context, this study opens a way for the further testing of more high-quality proteomics biomarkers, which could ultimately add value to the clinical management of PCa.</jats:p>
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    Serum chromogranin-A levels in neuroendocrine neoplasms as prognostic marker in correlation with the clinical course of the disease and the influence of octreotid therapy
    (Faculty of Medicine, University Ss. Cyril and Methodius in Skopje, 2021-05)
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    Introduction. Neuroendocrine neplasms (NEN) arise from neuroedocrine cells in various tissues and organs, have diverse biological behavior and express neuroendocrine markers synaptophysin and chromogranin A (CgA). Aim of the study. The aim of this study was to correlate the serum CgA levels before and after surgical and/or oncological treatment with octreotide and to determine the prognostic value of CgA variations during the follow-up. Material and methods. We used ELISA to analyze 699 serum samples from 410 patients during 9 years, due to carcinoid syndrome, benign neuroendocrine tumor (NET), localized neuroendocrine carcinoma (NEC) and patients with metastatic NEC (MS). Data from hospital databases were used for follow-up of 60 patients, divided into responders and non-responders, regarding their response to therapy. Results. The mean serum CgA value in 410 analyzed patients was by 3.47-fold increase compared to the maximal reference values. The highest increase was measured in patients with NEC/MS, with mean 12.94-fold increase, followed by patients with localized NECs, with mean 4.57. During follow-up, CgA values were reduced, with a significant difference between the groups of responders and non-responders. Conclusions. Reduction of the CgA level for at least 49.5% during the first 12 months after therapy was correlated with stable disease course, and serum CgA elevation or decrease less than 34% during the first 12 months after the therapy was correlated to unfavorable clinical course. Serum CgA levels are useful for the diagnosis of NENs and during the follow-up for detection of recurrence, disease progression and evaluation of the oncologic therapy response.