Research Paper Volume 15, Issue 21 pp 12413—12450
Construction and validation of a novel angiogenesis pattern to predict prognosis and immunotherapy efficacy in colorectal cancer
- 1 Department of Emergency Surgery, Peking University People’s Hospital, Xicheng, Beijing 100044, China
- 2 Department of Pancreatic and Gastrointestinal Surgery Division, Ningbo Second Hospital, Ningbo, Zhejiang 315010, China
- 3 Ningbo Key Laboratory of Intestinal Microecology and Human Major Diseases, Ningbo, Zhejiang 315010, China
- 4 Department of Emergency Medicine, Peking University People’s Hospital, Xicheng, Beijing 100044, China
- 5 Laboratory of Surgery Oncology, Peking University People’s Hospital, Xicheng, Beijing 100044, China
Received: April 12, 2023 Accepted: October 2, 2023 Published: November 7, 2023
https://doi.org/10.18632/aging.205189How to Cite
Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Evidence suggests that the tumor microenvironment (TME) affects the tumor active response to immunotherapy. Tumor angiogenesis is closely related to the TME. Nonetheless, the effects of angiogenesis on the TME of colorectal cancer (CRC) remain unknown.
Methods: We comprehensively assessed the angiogenesis patterns in CRC based on 36 angiogenesis-related genes (ARGs). Subsequently, we evaluated the prognostic values and therapeutic sensitivities of angiogenesis patterns using multiple methods. We then performed the machine learning algorithm and functional experiments to identify the prognostic key ARGs. Ultimately, the regulation of gut microbiota on the expression of ARGs was further investigated by using whole genome sequencing.
Results: Two angiogenesis clusters were identified and angiogenesis cluster B was characterized by increased stromal and immunity activation with unfavorable odds of survival. Further, an ARG_score including 9 ARGs to predict recurrence-free survival (RFS) was established and its predominant predictive ability was confirmed. The low ARG_score patients were characterized by a high mutation burden, high microsatellite instability, and immune activation with better prognosis. Moreover, patients with high KLK10 expression were associated with a hot tumor immune microenvironment, poorer immune checkpoint blocking treatment, and shorter survival. The in vitro experiments also indicated that Fusobacterium nucleatum (F.n) infection significantly induced KLK10 expression in CRC.
Conclusions: The quantification of angiogenesis patterns could contribute to predict TME characteristics, prognosis, and individualized immunotherapy strategies. Furthermore, our findings suggest that F.n may influence CRC progression through ARGs, which could serve as a clinical biomarker and therapeutic target for F.n-infected CRC patients.