摘要
背景：血管生成是癌症进展的最显著标志之一，有助于肿瘤转移和预后。抗血管生成药物已被证明对治疗转移性结直肠癌有效。然而，血管生成相关基因在肿瘤微环境中的潜在作用仍存在一些不确定性。
方法：我们分析了1214例大肠癌癌症样本，以确定血管生成相关基因（ARG）的变化，然后将血管生成与临床特征、预后和TME相关。使用三种计算方法（CIBERSORT、ssGSEA和MCPcounter）分析了大肠癌中ARG的表达谱，并提供了一个系统的免疫环境。根据血管生成相关基因的一致性聚类分析，CRC患者被分为两种亚型。所揭示的两种亚型之间的差异表达基因用于创建和验证ARGscore预后模型。此外，我们收集了8例癌症患者的标本，并进行了RT-qPCR以验证特征基因的表达。
结果：我们评估了ARG在癌症中的表达模式。我们确定了两种分子亚型，并证实ARGs的表达与预后和TME特征有关。基于不同亚型之间差异表达的基因，我们构建了ARG评分，并评估了其对癌症患者生存的预测能力。我们还开发了一个精确的列线图，使ARGscore在临床上更有用。此外，ARG评分与微卫星不稳定性、癌症干细胞和化疗药物敏感性显著相关。以免疫激活和微卫星不稳定为特征的ARGscore低的患者预后较好。
结论：ARG的表达影响癌症的预后、临床病理特征和肿瘤基质免疫微环境。我们开发了一种新的风险模型ARGscore，用于CRC患者的治疗和预后，并验证了其有希望的预测能力。这些发现将使我们更好地了解癌症，评估预后，并制定更有效的治疗方案。
Abstract
Background: Angiogenesis is one of the most prominent markers of cancer progression and contributes to tumor metastasis and prognosis. Anti-angiogenic drugs have proven effective in treating metastatic colorectal cancer. However, there is some uncertainty regarding the potential role of angiogenesis-related genes in the tumor microenvironment.

Methods: We analyzed 1,214 colorectal cancer samples to identify alterations in angiogenesis-related genes (ARGs), and then correlated angiogenesis with clinical features, prognosis, and TME. The ARGs expression profiles in colorectal cancer were analyzed using three computational methods (CIBERSORT, ssGSEA, and MCPcounter) and provided a systematic immune landscape. Patients with CRC were classified into two subtypes based on consensus clustering analysis of angiogenesis-related genes. The revealed differentially expressed genes between the two subtypes were used to create and validate ARGscore prognostic models. In addition, we collected eight colorectal cancer patient specimens and performed RT-qPCR to validate the signature gene expression.

Results: We assessed the expression patterns of ARGs in colorectal cancer. We identified two molecular subtypes and confirmed that the expression of ARGs was associated with prognosis and TME characteristics. Based on differentially expressed genes between subtypes, we constructed ARGscore and evaluated their predictive power for the survival of colorectal cancer patients. We also developed an accurate nomogram to make the ARGscore more clinically useful. In addition, ARGscore was significantly correlated with microsatellite instability, cancer stem cells, and chemotherapeutic drug sensitivity. Patients with ARGscore-low characterized by immune activation and microsatellite instability high had a better prognosis.

Conclusion: ARGs expression influenced the prognosis, clinicopathological features, and tumor stromal immune microenvironment in colorectal cancer. We developed a new risk model, ARGscore, for the treatment and prognosis of CRC patients and validated its promising predictive power. These findings will enable us to understand colorectal cancer better, assess prognoses, and develop more effective treatment options.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9992542/