Biomarkers for Early Detection of Cancer: A Systematic Review Towards the identification of true cancer biomarkers for early detection Louis-Philippe Fermon Student number: 01304166 Promotor: Prof. Inge Huybrechts Copromotor: Prof. Dr. Veronique Cocquyt A dissertation submitted to Ghent University in partial fulfilment of the requirements for the degree of Master of Medicine in Medicine. Academic year: 2017 – 2018 2 | P a g e Deze pagina is niet beschikbaar omdat ze persoonsgegevens bevat. Universiteitsbibliotheek Gent, 2021. This page is not available because it contains personal information. Ghent Universit , Librar , 2021. 4 | P a g e VOORWOORD “Sic parvis magna” “Greatness from small beginnings” After two years of intensive labour, I’m happy to finally present this dissertation. I would not have been able to do this without the help of my family, friends and of course, my promotor Prof. Dr. Inge Huybrechts. She was always eager to lend support, especially during though moments, and was available when I had any questions or needed any help. Furthermore, I would like to thank a few special people that aided me throughout this process. Firstly, my parents, without whom I would not have been able to bring it home. Secondly, I would like to thank my girlfriend Kimberley and all- time best friend Thomas, who’s advice and support were deeply appreciated. Lastly, I won’t forget all others who were there when I needed them the most. Thank you. 5 | P a g e 6 | P a g e Contents Abstract ........................................................................................................................................ 1 Abstract ........................................................................................................................................ 3 1. Introduction ............................................................................................................................... 4 1.1 Cancer as major health issue............................................................................................... 4 1.2 Early detection of cancer ..................................................................................................... 5 1.3 Biomarkers in screening for cancer ...................................................................................... 6 1.3.1 Definitions ..................................................................................................................... 6 1.3.2 Classification of Biomarkers .......................................................................................... 8 1.3.3 The Five Phases of Biomarker Development ................................................................ 9 1.4 Modern biomarkers obstacles ............................................................................................ 11 1.5 Searching reliable biomarkers............................................................................................ 12 2. Methods .................................................................................................................................. 13 2.1 Data sources and search strategy ..................................................................................... 13 2.2 Eligibility criteria ................................................................................................................. 13 2.3 Exclusion Criteria ............................................................................................................... 13 2.4 Data extraction .................................................................................................................. 14 2.5 Outcome Measures ........................................................................................................... 14 2.6 Results .............................................................................................................................. 14 2.7 Flow diagram ..................................................................................................................... 15 Identification ............................................................................................................................ 15 Screening ................................................................................................................................ 15 Eligibility .................................................................................................................................. 15 Included ................................................................................................................................... 15 3. Results .................................................................................................................................... 16 3.1 Colorectal cancer ............................................................................................................... 16 3.2 Hepatocellular cancer ........................................................................................................ 25 3.3 Lung cancer ....................................................................................................................... 33 3.4 Ovarian cancer .................................................................................................................. 39 3.5 Prostate Cancer ................................................................................................................. 46 3.6 Pancreatic cancer .............................................................................................................. 51 3.7 Breast Cancer .................................................................................................................... 58 3.8 Gastric Cancer ................................................................................................................... 63 3.9 Renal Cancer ..................................................................................................................... 68 7 | P a g e 3.10 Gynecologic cancer ......................................................................................................... 70 3.11 Bladder Cancer ................................................................................................................ 72 3.12 Oral Cancer ..................................................................................................................... 76 3.13 Esophageal Cancer ......................................................................................................... 79 3.14 Skin Cancer ..................................................................................................................... 80 3.15 Osteosarcoma ................................................................................................................. 81 3.16 Thyroid Cancer ................................................................................................................ 82 3.17 Leukemia ......................................................................................................................... 83 3.18 Various types of cancer ................................................................................................... 84 4. Discussion .............................................................................................................................. 87 4.1 Colorectal Cancer .............................................................................................................. 87 4.2 Hepatocellular cancer ........................................................................................................ 97 4.3 Lung cancer ..................................................................................................................... 103 4.4 Ovarian cancer ................................................................................................................ 110 4.5 Prostate cancer ............................................................................................................... 116 4.6 Pancreatic cancer ............................................................................................................ 120 4.7 Breast Cancer .................................................................................................................. 126 4.8 Gastric cancer ................................................................................................................. 130 4.9 Renal Cancer ................................................................................................................... 134 4.10 Gynecologic Cancer ...................................................................................................... 136 4.11 Bladder Cancer .............................................................................................................. 138 4.12 Oral Cancer ................................................................................................................... 141 4.13 Esophageal Cancer ....................................................................................................... 144 4.14 Skin Cancer ................................................................................................................... 145 4.15 Osteosarcoma ............................................................................................................... 145 4.16 Thyroid Cancer .............................................................................................................. 146 4.17 Leukemia ......................................................................................................................