Molecular characterization of genes related with angiogenesis, cold- hot tumor, and tumor immunity interactions in patients with TACE resistance in hepatocellular carcinoma

Abstract Background Tumor angiogenesis is an important factor in inducing tumor recurrence, metastasis and drug resistance, which directly affects the therapeutic effect of tumor patients. As a key treatment for liver cancer, TACE can prolong the survival time of some patients, but in patients with liver cancer after TACE, the relationship between TACE resistance and angiogenesis, tumor microenvironment, hot and cold tumors and immunotherapy is not clear. Methods We systematically evaluated 36 angiogenesis-related genes (ARGs) and comprehensively determined the correlation between angiogenesis and transcriptional patterns, prognosis and immune cell infiltration. ARGs score was used to quantify the angiogenic subtypes of each patient after TACE. Then we evaluated and verified their value in predicting the prognosis and treatment response of patients after TACE, and finally simulated the TACE environment to verify the effectiveness of the drug in vitro. Results We discussed the ARGs mutations in patients with TACE at the genetic level and determined their expression patterns in the TCGA and GEO cohorts. We identified two different molecular subtypes to distinguish between hot and cold tumors and observed that ARGs mutations were associated with clinicopathological features, prognosis and invasive TME. Secondly, an ARGs score was established to predict the overall survival time (OS), and its ability to reliably predict patients after TACE was confirmed. In addition, we have created a highly reliable Nomogram map to promote the clinical feasibility of ARGs score. Lower ARGs score, characterized by mutation burden and immune activation, proved superior OS. In addition, ARGs score was significantly correlated with immune score and drug sensitivity. At the same time, new drugs were screened to inhibit tumor angiogenesis and cooperate with immune anti-tumor therapy in TACE environment. Conclusion We determined that the high-risk group related with angiogenesis may be more suitable for immunotherapy and chemotherapy, and show the characteristics of hot tumor, which provides a reliable and simple method for HCC patients to evaluate the diagnosis and prognosis of tumor resistance to TACE, and to guide patients' choice of clinical treatment.