Multi-omics data integration towards biomarkers for colorectal adenoma-to-carcinoma progression

Abstract

Colorectal cancer is a major health concern worldwide. However, colorectal cancer has a high cure rate when detected in its early stages, which is why a population-wide screening program for this disease has been introduced in (a.o.) the Netherlands. Colorectal cancer develops from an adenoma, which is a non-invasive precursor of colorectal cancer. Removal of adenomas is an effective strategy to reduce colorectal cancer mortality rates. However, as only a minority of adenomas progress to cancer, such strategies may lead to overtreatment. High-risk adenomas, defined by specific molecular aberrations, have an increased risk of progressing to cancer. In this thesis, we extensively applied molecular (DNA, RNA, protein) profiling technologies followed by data integration to further characterize high-risk adenomas. We have shown that on molecular level high-risk adenomas in many aspects resemble cancers and express the same biomarkers, which are not expressed by healthy colon or adenomas with lower risk of progression. These biomarkers have promising potential to distinguish individuals with high-risk adenomas and colorectal cancers from healthy individuals and the ones with adenomas with lower risk of progressing, which in the future may be used to improve colorectal cancer screening programs.