Identification of novel prognostic and predictive biomarkers in colorectal cancer

Elmasry, Manal (2020): Identification of novel prognostic and predictive biomarkers in colorectal cancer. Dissertation, LMU München: Medizinische Fakultät

Abstract

For patients with colorectal cancer, the risk for disease recurrence and death mainly depends on disease stage. Yet, patients with early stage colon cancer may still succumb to the disease. Therefore, to improve the management of patients with colorectal cancer, new biomarkers for risk stratification are needed that are independent of tumor stage. Here, we demonstrate that RBP7 is a strong prognostic biomarker in colon cancer that functionally contributes to the malignant phenotype of colon cancer cells. We quantified RBP7 expression in colon cancer tissue by digital image analysis, and high levels of RBP7 protein and mRNA expressions were associated with poor cancer specific survival. Additionally, GSEA analysis and cell migration and invasion assays demonstrated that RBP7 is functionally linked to invasion and epithelial-mesenchymal transition in colon cancer. Furthermore, we illustrate here an unbiased approach using publically available TCGA data to identify new biomarkers that may aid in colorectal cancer risk stratification beyond clinical staging. By this approach Annexin A9 was identified and validated as an independent prognostic predictor of poor outcomes and that was associated with distant metastasis in independent colon cancer case collections on the protein level. Collectively, these findings provide a rationale for considering RBP7 and Annexin A9 as promising independent predictors for prognosis. These may be useful for risk stratification in patients with colorectal cancer and aid in improving patient management.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 23. März 2020
• 1. Bericht­erstatter:in: Horst, David