Li Luanfeng, Liu Wensi, Tang Haichao, Wang Xiangyi, Liu Xinli, Yu Zhaojin, Gao Yanan, Wang Xiaobin, Wei Minjie
Department of Pharmacology, School of Pharmacy, China Medical University Shenyang 110122, Liaoning, China.
Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation Shenyang 110122, Liaoning, China.
Am J Cancer Res. 2021 Oct 15;11(10):5076-5093. eCollection 2021.
Hypoxia is a common feature of tumor microenvironment (TME). This study aims to establish the genetic features related to hypoxia in Bladder urothelial carcinoma (BLCA) and investigate the potential correlation with hypoxia in the TME and immune cells. We established a BLCA outcome model using the hypoxia-related genes from The Cancer Genome Atlas using regression analysis and verified the model using the Gene Expression Omnibus GSE32894 cohort. We measured the effect of each gene in the hypoxia-related risk model using the Human Protein Atlas website. The predictive abilities were compared using the area under the receiver operating characteristic curves. Gene Set Enrichment Analysis was utilized for indicating enrichment pathways. We analyzed immune cell infiltration between risk groups using the CIBERSORT method. The indicators related to immune status between the two groups were also analyzed. The findings indicated that the high-risk group had better outcomes than the low-risk group in the training and validation sets. Each gene in the model affected the survival of BLCA patients. Our hypoxia-related risk model had better performance compared to other hypoxia-related markers (HIF-1α and GLUT-1). The high-risk group was enriched in immune-related pathways. The expression of chemokines and immune cell markers differed significantly between risk groups. Immune checkpoints were more highly expressed in the high-risk group. These findings suggest that the hypoxia-related risk model predicts patients' outcomes and immune status in BLCA risk groups. Our findings may contribute to the treatment of BLCA.
缺氧是肿瘤微环境（TME）的一个常见特征。本研究旨在确定膀胱尿路上皮癌（BLCA）中与缺氧相关的基因特征，并研究其与TME中的缺氧及免疫细胞的潜在相关性。我们使用来自癌症基因组图谱的缺氧相关基因，通过回归分析建立了一个BLCA预后模型，并使用基因表达综合数据库GSE32894队列对该模型进行了验证。我们使用人类蛋白质图谱网站测量了缺氧相关风险模型中每个基因的作用。使用受试者工作特征曲线下面积比较预测能力。利用基因集富集分析来指示富集途径。我们使用CIBERSORT方法分析了风险组之间的免疫细胞浸润情况。还分析了两组之间与免疫状态相关的指标。研究结果表明，在训练集和验证集中，高危组的预后优于低危组。模型中的每个基因都影响BLCA患者的生存。与其他缺氧相关标志物（HIF-1α和GLUT-1）相比，我们的缺氧相关风险模型表现更好。高危组在免疫相关途径中富集。趋化因子和免疫细胞标志物的表达在风险组之间存在显著差异。免疫检查点在高危组中表达更高。这些发现表明，缺氧相关风险模型可预测BLCA风险组患者的预后和免疫状态。我们的发现可能有助于BLCA的治疗。
