Retrospektive Analyse von an der Universitätsmedizin Göttingen (UMG) behandelten Patienten und Patientinnen mit kolorektalen Karzinomen im Zeitraum 2000 bis 2020 und Korrelation der klinischen Parameter mit Proteinanalysen
von Linde-Allegra Rosen
Datum der mündl. Prüfung:2022-06-23
Betreuer:Dr. Lena-Christin Conradi
Gutachter:Dr. Lena-Christin Conradi
Gutachter:Prof. Dr. Philipp Ströbel
EnglischBackground: In regard of the Warburg-effect and the progressively more personalised therapy and prognostic options available, based on molecular biology research, the EGFR- and Glycolysis receptor proteins present an ever more important basement for the understanding of colorectal carcinoma. Patients and methods: In this thesis, the clinical-pathological parameters of 697 patients were gathered and analysed in the sense of a follow-up study. The data is coherent with the literature and is therefore representative. The collective consists of 409 (58,5%) male and 288 (41,5%) female patients. The mean age of primary disease is 68. 60% of the tumours were of the pT III state, 18% of the ptII and pTIV state, respectively. By means of Proteomics, the strength of the protein expression can be analysed in comparison to the clinical-pathological parameters. The company Biognosys analysed 1000 patients with a Colo-rectal carcinoma by means of an untargeted protein analysis. After application of the in-/ exclusion criteria, the dataset of 697 emerged. The analysed proteins are ALDOA, ALDOB, ALDOC, ENO1, ENO2, GAPDH, GPI, HK1, HK2, HK3, PFKFB2, PFKFB4, PGAM1, PGAM5, PGK1, PGK2, PKLR, TPI1, ERBB2, ERBB3 und EGFR. Results: Of the glycolysis proteins, statistically significant expressions were found for the state of the tumour, the grading and the localisation. This can be seen as a confirmation of the Warburg-effect on the protein level. For the EGFR-proteins, slightly increased expressions were found for the state of the tumour, the number of lymph node metastases, the Grading and the UICC-state. The survival time analysis showed a statistically significant shortening of the disease free survival, the cancer specific survival and the overall survival in relation to the clinical-pathological parameters. Furthermore, a shortening of the disease free survival and the overall survival could be shown for increased expressions of the proteins ALDOB, ENO2, HK1, HK3, PGK1, PKLR and the total-EGFR-proteins. Summary: Increased expressions of the metabolic proteins of the glycolysis and of EGFR-receptor proteins represent an unfavourable bio-marker.
Keywords: Proteomics; colorectal carcinoma; metabolic proteins; Warburg-effect; survival time analysis