Hepatobiliary Surgery, Hunan Provincial People's Hospital (The First Affiliate Hospital of Hunan Normal University), Changsha, China.
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China.
J Immunol Res. 2022 Aug 23;2022:5209607. doi: 10.1155/2022/5209607. eCollection 2022.
Hypoxia and angiogenesis are the leading causes of tumor progression, and their strong correlation has been discovered in many cancers. However, their collective function's prognostic and biological roles were not reported in gastric cancer. Hence, we aimed to investigate the effects of hypoxia and angiogenesis on gastric cancer via sequencing data. This study used weighted gene coexpression network analysis and random forest regression to build a hypoxia-angiogenesis-related model (HARM) via the TCGA-STAD lncRNA data. It estimated the HARM's correlation with clinical features and its accuracy for survival prediction. Sequential functional analyses were conducted to investigate its biological role, and we next sought the immune landscape status and immunological function variation by ESTIMATE score calculation and GSVA, respectively. Seven different algorithms were conducted to assess the immunocyte infiltration, and TIDE score and immune checkpoint levels were compared between the high- and low-HARM groups. As a result, we found that HARM predicted patient survival with high accuracy and was correlated with higher stages of gastric cancer. Various cancer-associated pathways and macrophage-related regulations were upregulated in the high-HRAM group. The high-HARM group harbored higher immune levels, and M2 macrophages and cancer-associated fibroblasts were particularly highly unfiltered. Furthermore, globally upregulated immune checkpoints and higher TIDE scores were observed in the high-HARM group. Finally, we filtered eight drugs with lower IC50 in the high-HARM group as potential drugs for the HARM-targeted therapy. We believe this study opens up novel perspectives into the interaction between hypoxia-angiogenesis and immunosuppression and will provide novel insights for gastric cancer immunotherapy.
缺氧和血管生成是肿瘤进展的主要原因，它们在许多癌症中都有很强的相关性。然而，它们在胃癌中的集体功能的预后和生物学作用尚未报道。因此，我们旨在通过测序数据研究缺氧和血管生成对胃癌的影响。本研究使用加权基因共表达网络分析和随机森林回归，通过 TCGA-STAD lncRNA 数据构建了一个缺氧-血管生成相关模型 (HARM)。它估计了 HARM 与临床特征的相关性及其对生存预测的准确性。进行了顺序功能分析以研究其生物学作用，我们接下来通过 ESTIMATE 评分计算和 GSVA 分别寻求免疫景观状态和免疫功能变化。通过七种不同的算法评估免疫细胞浸润，比较高 HARM 和低 HARM 组之间的 TIDE 评分和免疫检查点水平。结果发现，HARM 以高精度预测患者生存，与胃癌的较高阶段相关。在高 HARM 组中，各种癌症相关途径和巨噬细胞相关调节被上调。高 HARM 组具有更高的免疫水平，M2 巨噬细胞和癌症相关成纤维细胞特别高度未过滤。此外，在高 HARM 组中观察到全局上调的免疫检查点和更高的 TIDE 评分。最后，我们筛选出高 HARM 组中 IC50 较低的八种药物作为 HARM 靶向治疗的潜在药物。我们相信这项研究为缺氧-血管生成和免疫抑制之间的相互作用开辟了新的视角，并将为胃癌免疫治疗提供新的见解。
