Yang Yi, Qiu Yu-Ting, Li Wen-Kun, Cui Zi-Lu, Teng Shuo, Wang Ya-Dan, Wu Jing
Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing 100050, China.
Department of Gastroenterology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100050, China.
World J Gastrointest Oncol. 2024 Jul 15;16(7):3169-3192. doi: 10.4251/wjgo.v16.i7.3169.
Angiogenesis plays an important role in colon cancer (CC) progression.
To investigate the tumor microenvironment (TME) and intratumor microbes of angiogenesis subtypes (AGSs) and explore potential targets for antiangiogenic therapy in CC.
The data were obtained from The Cancer Genome Atlas database and Gene Expression Omnibus database. K-means clustering was used to construct the AGSs. The prognostic model was constructed based on the differential genes between two subtypes. Single-cell analysis was used to analyze the expression level of on different cells in CC, which was validated by immunofluorescence. Its biological functions were further explored in HUVECs.
CC samples were grouped into two AGSs (AGS-A and AGS-B) groups and patients in the AGS-B group had poor prognosis. Further analysis revealed that the AGS-B group had high infiltration of TME immune cells, but also exhibited high immune escape. The intratumor microbes were also different between the two subtypes. A convenient 6-gene angiogenesis-related signature (ARS), was established to identify AGSs and predict the prognosis in CC patients. was selected as the representative gene of ARS, which was higher expressed in endothelial cells and promoted the migration of HUVECs.
Our study identified two AGSs with distinct prognoses, TME, and intratumor microbial compositions, which could provide potential explanations for the impact on the prognosis of CC. The reliable ARS model was further constructed, which could guide the personalized treatment. The might be a potential target for antiangiogenic therapy.
血管生成在结肠癌（CC）进展中起重要作用。
研究血管生成亚型（AGSs）的肿瘤微环境（TME）和肿瘤内微生物，并探索CC抗血管生成治疗的潜在靶点。
数据来自癌症基因组图谱数据库和基因表达综合数据库。采用K均值聚类构建AGSs。基于两个亚型之间的差异基因构建预后模型。采用单细胞分析来分析CC中不同细胞上的表达水平，并通过免疫荧光进行验证。在人脐静脉内皮细胞（HUVECs）中进一步探索其生物学功能。
CC样本被分为两个AGSs组（AGS-A和AGS-B），AGS-B组患者预后较差。进一步分析显示，AGS-B组TME免疫细胞浸润高，但也表现出高免疫逃逸。两个亚型之间的肿瘤内微生物也不同。建立了一个便捷的6基因血管生成相关特征（ARS），以识别AGSs并预测CC患者的预后。被选为ARS的代表性基因，其在内皮细胞中高表达并促进HUVECs的迁移。
我们的研究确定了两种预后、TME和肿瘤内微生物组成不同的AGSs，这可能为影响CC预后提供潜在解释。进一步构建了可靠的ARS模型，可指导个性化治疗。可能是抗血管生成治疗的潜在靶点。
