Development of a novel prognostic signature for colorectal cancer based on angiogenesis-related genes

Abstract

Background: Colorectal cancer (CRC) is the third most common malignant tumor worldwide. Angiogenesis is closely related to tumor metastasis, which is the main cause of cancer death. Although several angiogenesis signatures have been proposed in some cancer types, no angiogenic signature has been developed to predict the prognosis and efficacy of antiangiogenic bevacizumab in CRC patients. Methods: We developed a novel CRC angiogenic signature by refining seven publicly available angiogenic gene sets using least absolute shrinkage and selection operator (LASSO). Immune and stromal cells within the tumor microenvironment were compared between the high- and low-risk groups in more than 1000 CRC samples classified by calculating the risk score based on the customized angiogenic signature. The correlation of this new gene set with the efficacy of bevacizumab was also compared. Results: A new prognostic-associated angiogenesis signature gene set was constructed that can divide CRC patients into two high- and low-risk groups. The high-risk angiogenic group was significantly associated with extracellular matrix organization, epithelial-mesenchymal transition (EMT), and myogenesis. In addition, the high-risk group had higher infiltration of stromal and immune cells and was more resistant to bevacizumab than the low-risk group. Conclusion: Briefly, we constructed a novel angiogenic signature that can predict the prognosis of CRC patients and the efficacy of bevacizumab in treating CRC. Our results provide new insights into the relationships among angiogenesis, metastasis, and medication for CRC.

Keywords

• Colorectal cancer
• Angiogenesis
• Prognosis
• Tumor microenvironment