摘要
出身背景
肿瘤血管生成是诱导肿瘤复发、转移和耐药的重要因素，直接影响肿瘤患者的治疗效果。TACE作为癌症的关键治疗手段，可以延长部分患者的生存时间，但在TACE后的癌症患者中，TACE抵抗与血管生成、肿瘤微环境、冷热肿瘤和免疫治疗之间的关系尚不明确。
方法
我们系统地评估了36个血管生成相关基因（ARGs），并全面确定了血管生成与转录模式、预后和免疫细胞浸润之间的相关性。ARGs评分用于量化TACE后每位患者的血管生成亚型。然后我们评估和验证了它们在预测TACE后患者预后和治疗反应方面的价值，并最终模拟了TACE环境，以验证药物在体外的有效性。
后果
我们在遗传水平上讨论了TACE患者的ARGs突变，并确定了它们在TCGA和GEO队列中的表达模式。我们确定了两种不同的分子亚型来区分热肿瘤和冷肿瘤，并观察到ARGs突变与临床病理特征、预后和侵袭性TME有关。其次，建立ARGs评分来预测总生存时间（OS），并证实其可靠预测TACE后患者的能力。此外，我们创建了一个高度可靠的诺模图，以促进ARGs评分的临床可行性。以突变负荷和免疫激活为特征的ARGs评分较低，被证明具有优越的OS。此外，ARGs评分与免疫评分和药物敏感性显著相关。同时，筛选出抑制肿瘤血管生成的新药，并在TACE环境下配合免疫抗肿瘤治疗。
结论
我们确定与血管生成相关的高危人群可能更适合免疫治疗和化疗，并表现出热肿瘤的特征，这为HCC患者评估肿瘤对TACE耐药性的诊断和预后，指导患者选择临床治疗提供了一种可靠而简单的方法。
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.

https://www.researchsquare.com/article/rs-2603521/v1