Verfügbarkeit: Uncovering the proteome of primary prostate cancer and lymph node metastases

Uncovering the proteome of primary prostate cancer and lymph node metastases:

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Bibliographische Detailangaben
1. Verfasser:	Müller, Ann-Kathrin (VerfasserIn)
Format:	Abschlussarbeit Buch
Sprache:	English
Veröffentlicht:	Freiburg i. Br [2019?]
Schlagworte:	Hochschulschrift
Online-Zugang:	Inhaltsverzeichnis Inhaltsverzeichnis
Beschreibung:	93 Seiten Illustrationen, Diagramme 30 cm

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Datensatz im Suchindex

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adam_text	CONTENTS PREFACE ....................................................................................................................................................... 1 SUMMARY ....................................................................................................................................................6 ZUSAMMENFASSUNG ....................................... 7 ABBREVIATIONS ........................................................................................................................................... 8 I. INTRODUCTION ............................................................................................................................ 11 (1) PROSTATE CANCER - CLINICAL ASPECTS ...................................................................................... 11 1.1 INCIDENCE AND MORTALITY .................................................................................................................. 11 1.2 PATHOLOGY OF PRIMARY PCA .............................................................................................................. 11 1.3 METASTASES FORMATION ..................................................................................................................... 13 1.4 RISK FACTORS ....................................................................................................................................... 13 1.5 SYMPTOMS ........................................................................................................................................ 14 1.6 DIAGNOSIS .......................................................................................................................................... 14 1.7 TREATMENT ......................................................................................................................................... 14 1.8 PROGNOSIS ......................................................................................................................................... 15 (2) PROSTATE CANCER - TUMOR BIOLOGY ......................................................................................... 15 2.1 ANDROGEN RECEPTOR (AR) .................................................................................................................. 16 2.2 ETS GENE FUSIONS ............................................................................................................................. 16 2.3 BREAST-CANCER-RELATED-ANTIGEN 1/2 ( BRCA1/2 ) ............................................................................... 17 2.4 MYC ONCOGENE ................................................................................................................................ 17 (3) PROTEOMICS ................................................................................................................................ 18 3.1 MASS-SPECTROMETRY-BASED PROTEOMICS ........................................................................................... 18 3.2 PEPTIDE QUANTIFICATION USING STABLE-ISOTOPIC LABELING .................................................................... 18 3.3 LABEL-FREE PEPTIDE QUANTIFICATION ..................................................................................................... 19 3.4 PROTEOMICS OF FORMALIN-FIXED-PARAFFIN-EMBEDDED (FFPE) TISSUE .................................................. 19 (4) OBJECTIVES OF THIS STUDY ......................................................................................................... 20 II. MATERIALS .................................................................................................................................... 21 (1) INSTRUMENTS ............................................................................................................................... 21 (2) DISPOSABLES .............................................................................................................................. 22 (3) CHEMICALS AND REAGENTS ....................................................................................................... 23 (4) ANTIBODIES ................................................................................................................................. 25 (5) BUFFERS AND SOLUTIONS ............................................................................................................. 25 (6) SOFTWARE ..................................................................................................................................... 27 III. METHODS ...................................................................................................................................... 28 (1) PATIENTS COHORT .......................................................................................................................... 28 (2) WET LAB .................................................................................. 29 2.1 TISSUE COLLECTION AND FIXATION .......................................................................................................... 29 2.2 MACRODISSECTION OF TUMOR TISSUE ..................................................................................................... 31 2.3 SAMPLE PREPARATION PROTOCOLS FOR MASS-SPECTROMETRY ANALYSIS .................................................... 31 A) PROTOCOL 1 ............................................................................................................................ 31 B) PROTOCOL 2 ............................................................................................................................36 C) CHOICE OF PROTOCOL ............................................................................................................. 38 2.4 PROTEIN CONCENTRATION ASSAYS .......................................................................................................... 39 A) BRADFORD PROTEIN ASSAY .................................................................................................... 39 B) BICINCHONINIC ACID ASSAY (BCA) ...................................................................................... 39 2.5 GEL PREPARATION ................................................................................................................................ 39 2.6 SILVER STAINING ...................................................................................................................................40 2.7 SDS-PAGE .......................................................................................................................................40 2.8 IMMUNOHISTOCHEMISTRY .................................................................................................................... 40 A) PRINCIPLE AND STAINING PROTOCOLS ....................................................................................... 40 B) INTERPRETATION AND ANALYSIS OF IMMUNOHISTOCHEMICAL STAININGS .................................. 42 (3) LC-MS/MS DATA ACQUISITION .................................................................................................. 43 (4) DATA ANALYSIS ............................................................................................................................ 43 4.1 PEPTIDE AND PROTEIN IDENTIFICATION AND QUANTIFICATION SOFTWARE ......................................................43 4.2 DATA QUALITY CONTROL .......................................................................................................................... 44 4.3 DIFFERENTIAL ABUNDANCES OF PROTEINS ............................................................................................... 45 4.4 STATISTICAL ANALYSIS ............................................................................................................................ 45 4.5 BIOLOGICAL DATA INTERPRETATION SOFTWARE ...........................................................................................45 A) INGENUITY PATHWAY ANALYSIS .............................................................................................. 46 B) GO ENRICHMENT / KEGG ANALYSIS ..................................................................................... 47 C) DAVID BIOINFORMATICS RESOURCES 6.7 ............................................................................. 47 D) STRING DATABASE ............................................................................................................. 48 IV. RESULTS ........................................................................................................................................ 49 (1) GENERAL APPROACH .................................................................................................................... 49 (2) DATA QUALITY AND PROTEIN YIELD ............................................................................................... 49 2.1 QUALITY CONTROL ..................................................................................................................................49 2.2 PROTEIN IDENTIFICATION FROM FFPE SAMPLES ........................................... 49 2.3 DIFFERENTIALLY REGULATED PROTEINS ...................................................................................................... 51 (3) BIOLOGICAL MOTIFS .................................................................................................. 53 3.1 * RECURRENT LNM * VS. TU WITH LNM .............................................................................................. 53 3.2 * TU WITH LNM * VS. * TU WITHOUT LNM * .............................................................................................. 58 (4) INDIVIDUAL PROTEIN LEVEL ........................................................................................................... 59 4.1 * RECURRENT LNM VS. TU WITH LNM ............................................................................................... 59 4.2 TU WITH LNM VS. TU WITHOUT LNM * ............................................................................................. 60 (5) IMMUNOHISTOCHEMISTRY INVESTIGATION OF DIFFERENTIALLY ABUNDANT PROTEINS ................. 62 V. DISCUSSION ......................................................................... 66 (1) DECISION FOR LABEL-FREE QUANTIFICATION .................................................................................. 66 (2) QUALITY CONTROL REVEALS GOOD QUALITY DATA ........................................................................... 67 (3) DATA ANALYSIS ISSUES ................................................................................................................ 67 (4) SUCCESSFUL PROTEOME ANALYSIS OF FFPE TISSUE ................................................................. 68 (5) NODAL METASTASIZING PRIMARY PCA AND CORRESPONDING LNM EXHIBIT DIFFERENT PROTEOME MOTIFS ............................................................................................................................... 68 (6) ALTERED BIOLOGICAL PROCESSES IN METASTASIZED PRIMARY PCA COMPARED TO NON METASTASIZED, RELAPSE-FREE PRIMARY PCA ..................................................................................... 70 (7) THE POTENTIAL ROLE OF PROTEINS ENRICHED IN RECURRENT LNM COMPARED TO METASTASIZED PRIMARY PCA ....................................................................................................................................... 70 A) PARR AND PARP-INHIBITORS IN PCA ................................................................................. 70 B) NDRG3 - A POTENTIAL STARTING POINT FOR NEW THERAPEUTIC APPROACHES? ....................... 72 (8) THE POTENTIAL ROLE OF PROTEINS ENRICHED IN METASTASIZED, NODAL RELAPSING PRIMARY PCA COMPARED TO NON-METASTASIZING, RELAPSE-FREE PRIMARY PCA ......................................... 73 A) PS MA - AN ALREADY VALUABLE DIAGNOSTIC MARKER .......................................................... 73 B) RDH1 1 - A POTENTIAL MARKER FOR ADVANCED PCA? ......................................................... 74 VI. CONCLUSIONS .............................................................................................................................. 75 VII. REFERENCES ........................................................................................................................... 76 VIII. SUPPLEMENTARY MA TER!AL .............................................................................................. 88 (1) 81: DATA QUALITY CONTROL WITH PTXQC ................................................................................. 88 (2) 82: DIFFERENTIALLY EXPRESSED PROTEINS * RECURRENT LNM * VS. * TU WITH LNM * ............. 89 (3) S3: DIFFERENTIALLY EXPRESSED PROTEINS IN * TU WITH LNM * VS. * TU WITHOUT LNM * ..... 90 IX. EIDESSTATTLICHE VERSICHERUNG ................................................................................... 91 X. ERKLARUNG ZUM EIGENTANTEIL AN DISSERTATION UND PUBLIKATION .............. 92 XI. ACKNOWLEDGEMENTS / DANKSAGUNG ........................................................................... 93
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author	Müller, Ann-Kathrin
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spelling	Müller, Ann-Kathrin Verfasser (DE-588)1186647566 aut Uncovering the proteome of primary prostate cancer and lymph node metastases vorgelegt 2017 von Ann-Kathrin Müller Freiburg i. Br [2019?] 93 Seiten Illustrationen, Diagramme 30 cm txt rdacontent n rdamedia nc rdacarrier Dissertation Albert-Ludwigs-Universität Freiburg i. Br. 2019 (DE-588)4113937-9 Hochschulschrift gnd-content B:DE-101 application/pdf http://d-nb.info/1187370231/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=031421380&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis
spellingShingle	Müller, Ann-Kathrin Uncovering the proteome of primary prostate cancer and lymph node metastases
subject_GND	(DE-588)4113937-9
title	Uncovering the proteome of primary prostate cancer and lymph node metastases
title_auth	Uncovering the proteome of primary prostate cancer and lymph node metastases
title_exact_search	Uncovering the proteome of primary prostate cancer and lymph node metastases
title_full	Uncovering the proteome of primary prostate cancer and lymph node metastases vorgelegt 2017 von Ann-Kathrin Müller
title_fullStr	Uncovering the proteome of primary prostate cancer and lymph node metastases vorgelegt 2017 von Ann-Kathrin Müller
title_full_unstemmed	Uncovering the proteome of primary prostate cancer and lymph node metastases vorgelegt 2017 von Ann-Kathrin Müller
title_short	Uncovering the proteome of primary prostate cancer and lymph node metastases
title_sort	uncovering the proteome of primary prostate cancer and lymph node metastases
topic_facet	Hochschulschrift
url	http://d-nb.info/1187370231/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=031421380&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA
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