We set out the get a better understanding of the role of Bone Morphogenetic Protein(BMP) signalling in normal intestine and in carcinogenesis. The BMP pathway isknown to be a major player in the... Show moreWe set out the get a better understanding of the role of Bone Morphogenetic Protein(BMP) signalling in normal intestine and in carcinogenesis. The BMP pathway isknown to be a major player in the development of colorectal cancer (CRC). CRC isone of the leading causes of cancer-related deaths in the western world. Althoughsurvival and recurrence of CRC have improved, 5-year survival is low at only 65%(https://seer.cancer.gov – US data). Improving our understanding of the molecularpathways involved in CRC will potentially allow earlier detection, better predictionand personalized therapy. To briefly summarise the research we have done, we startedby investigating the function of BMP in the normal intestine. We then went on tostudy the role of BMP signalling in carcinogenesis, mainly the role of non canonicalBMP signalling in the development of metastasis. We ended with a focus on patientsby explaining how we can improve estimation of prognosis using expression levelsof several BMP components and how targeting the BMP pathway can be used forpersonalized treatment of patients. Show less
Colorectal tumours with high stromal content have a poor prognosis. In part 1, I investigated, at the protein and gene expression levels, the composition of these tumours in comparison to stroma... Show moreColorectal tumours with high stromal content have a poor prognosis. In part 1, I investigated, at the protein and gene expression levels, the composition of these tumours in comparison to stroma-low tumours. In part 2, KRAS mutant colorectal cancer cell lines had a different metabolism compared to KRAS wild type after inhibition of mTORC1. This may contribute to therapeutic resistance. Show less
Potential relevant biomarkers can be found at different levels in tumour developmentand disease progression. This thesis is divided into three overarching parts. Colorectalcancer was studied from... Show morePotential relevant biomarkers can be found at different levels in tumour developmentand disease progression. This thesis is divided into three overarching parts. Colorectalcancer was studied from a population-based perspective (part I) to a molecular level,detailed as protein expression (part II) and (epi)genetics (part III), as indicated in Figure 2.In part I the use of adjuvant chemotherapy in patients with locally advanced rectalcancer, who underwent resection after preoperative (chemo)radiotherapy, wasevaluated in a meta-analysis based on individual patient data. Since four randomizedcontrolled trials individually did not end the ongoing debate about the role of adjuvantchemotherapy 14,68-70. In part II the ability by tumour cells to evade the immunerecognition was studied, especially the role of the non-classical HLA class I moleculeHLA-G was studied in detail. In part III, an epigenetic biomarker, LINE-1 methylationlevel, was studied in a dedicated stage II colon cohort. In addition, an establishedgenetic biomarker for colon cancer, MSI, was studied in a large rectal cancer cohort. Show less
