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: Faculty of Medicine

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.

• Item Type: Theses (Dissertation, LMU Munich)
• Subjects: 600 Technology, Medicine; 600 Technology, Medicine > 610 Medical sciences and medicine
• Faculties: Faculty of Medicine
• Language: English
• Date of oral examination: 23. March 2020
• 1. Referee: Horst, David
• Signature of the printed copy: 0700/UMD 19032