SEARCH FOR THE NOVEL PROTEIN MARKERS THAT MAY ALLOW EARLY DIAGNOSIS OF BREAST CANCER BY USING COMPARATIVE SEROLOGICAL PROTEOME ANALYSIS OF BREAST CANCER TISSUES

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Tezin Türü: Doktora

Tezin Yürütüldüğü Kurum: Kocaeli Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri, Türkiye

Tezin Onay Tarihi: 2020

Tezin Dili: İngilizce

Öğrenci: KÜBRA KARAOSMANOĞLU YÖNETEN

Danışman: Murat Kasap

Özet:

Breast cancer (BC) incidence and mortality rates have been increasing due to lack of appropriate diagnostic tools for early detection. Proteomics-based studies may provide novel targets for early diagnosis and efficient treatment. The aim of this study was to discover potential diagnostic/prognostic biomarkers for BC. BC tissues, their corresponding healthy counterparts and sera samples were collected and subtyped. Two-dimensional gel electrophoresis (2-DE) and difference gel electrophoresis (DIGE) coupled to matrix assisted lase desorption/ionization mass spectrometry (MALDI-TOF/TOF), and enhanced-serological proteome analysis (E-SERPA) coupled to nano liquid chromatography mass spectrometry (nLC-MS/MS) were used as the experimental approaches. ELISA was used to assess the prognostic and diagnostic values of the proposed biomarkers. Biostatistical analyses performed with differentially regulated proteins, GPD1 and MAGL, presented high evidence for their diagnostic and prognostic values as biomarkers. Alpha-tubulin (TUBA1A), cyclophilin A (PPIA), histone H4 (H4C1), clusterin (CLU), periostin (POSTN), macrophage migration inhibitory factor (MIF), splicing factor serine/arginine rich 3 (SFRS3), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and coiled-coil domain containing protein 13 (CCDC13) were identified as tumor-associated antigenic proteins by E-SERPA assay. The work presented here analysed the changes occurring in proteome of BC subtypes. The findings placed an emphasis on the relationship among triacylglycerol metabolism and BC-subtypes and detailed the changes occurring in two key proteins, GPD1 and MAGL. Significant regulation in expression levels of PPIA, SFRS3 and POSTN were verified in BC subtypes. This work allowed us to extend our knowledge of BC metabolism and propose biomarkers which have high potentials to become diagnostic and/or prognostic biomarkers.