Abstract
Colorectal cancer is a highly malignant cancer with poor prognosis and mortality rates. As the first biological agent approved for metastatic colorectal cancer (mCRC), bevacizumab was confirmed to exhibit good performance when combined with chemotherapy and immunotherapy. However, the efficacy of both bevacizumab and immunotherapy is highly heterogeneous across CRC patients with different stages. Thus, exploring a novel biomarker to comprehensively assess the prognosis and bevacizumab and immunotherapy response of CRC is of great significance. In our study, weighted gene co-expression network analysis (WGCNA) and the receiver operating characteristic (ROC) curves were employed to identify bevacizumab-related genes. After verification in four public cohorts and our internal cohort, ALOX12 was identified as a key gene related to bevacizumab response. Prognostic analysis and in vitro experiments further demonstrated that ALOX12 was closely associated with the prognosis, tumor proliferation, invasion, and metastasis. Multi-omics data analysis based on mutation and copy number variation (CNV) revealed that RYR3 drove the expression of ALOX12 and the deletion of 17p12 inhibited ALOX12 expression, respectively. Moreover, we interrogated the relationship between ALOX12 and immune cells and checkpoints. The results exhibited that high ALOX12 expression predicted a higher immune infiltration and better immunotherapy response, which was further validated in Tumor Immune Dysfunction and Exclusion (TIDE) and Subclass Mapping (SubMap) methods. Above all, our study provides a stable biomarker for clinical protocol optimization, prognostic assessment, precise treatment, and individualized treatment of CRC.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.