Improving diagnostic, prognostic and predictive biomarkers in colorectal cancer: the role of proteomics and stromatogenesis

Huijbers, A. (2022)

Doctoral Thesis

This thesis highlights, firstly, the importance of early CRC detection by presenting results of a CRC diagnostic proteomic biomarker signature with high discriminative power. Secondly, a strong robust, independent prognostic tumor stroma ratio (TSR) biomarker, which confirms to be of important clinical value. The TSR has the ability to stratify colon cancer patients according to their prognostic outcome in a highly reproducible and low-cost manner. It has shown to link patients with a high intra tumor stromal content and a worse prognosis. Literature shows a wealth of evidence that supports this prognostic value in CRC as well as in other cancers. This PhD research therefore concludes that it should be implemented in the official guidelines of the TNM classification to improve stratification for CRC patients in daily routine pathological evaluation. The prospective, international, multicentre UNITED study will hopefully overcome the last hurdle for this clinical implementation. Lastly, this thesis offers more insight in the elusiveness of the tumor microenvironment and stromatogenesis that contributes to the aggressiveness of some CRC tumors. The biological differences, interconnections and changes in the microenvironment presented give multiple leads for further research and new personalized treatment possibilities.

• Stroma
• Proteomics
• Colorectal cancer
• Diagnostic
• Prognostic
• Predictive
• Biomarker
• Stromatogenesis
• Screening
• Early detection

• All authors: Huijbers, A.
• Supervisor: Tollenaar, R.A.E.M.
• Co-supervisor: Mesker, W.E.
• Committee: Leerdam, M.E. van; Hoeven, J.J.M. van der; Peeters, K.C.M.J.; Terpstra, V.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2022-06-02
• ISBN (print): 9789463616553