多囊卵巢综合征和久坐行为的共享基因作为子宫内膜癌的新型免疫景观生物标志物。
Shared genes of polycystic ovary syndrome and sedentary behavior as a novel immune landscape biomarker for endometrial cancer.
发表日期:2024 Aug 17
作者:
Yao Ge, Yuan Chen, Yun Zhang, Yifang Hu, Feng Jiang, Xiao Lu, Chuyan Wu
来源:
GENES & DEVELOPMENT
摘要:
子宫内膜癌(EC)与多囊卵巢综合征(PCOS)和久坐行为等重要危险因素相关。在我们的研究中,我们的目标是采用机器学习算法来研究它们相互作用的潜在分子过程,并探索它们各自在 EC 诊断和免疫治疗中的作用。 GEO 数据库提供对微阵列数据的访问,该数据在本研究中使用加权基因表达网络分析 (WGCNA) 来识别与 PCOS 和久坐行为相关的基因表达模块。然后使用 Cluego 软件研究 PCOS 和久坐个体共享途径的能量富集情况,并使用差异基因分析来确认另外两个数据库。构建了 miRNA-mRNA 控制网络来验证该通路。然后分析了 EC 中共享途径的免疫相关因素。最后,为了验证我们的发现,我们使用 EC 细胞系(AN3CA、KLE、Ishikawa、RL95-2 和 HEC-1A)进行了细胞实验。我们发现细胞内芳香化合物合成代谢增加是多囊卵巢综合症和久坐个体的共同特征。然后,我们根据多囊卵巢综合症和久坐行为的共同遗传特征开发了一个疾病途径模型。我们对 EC 样本进行了通路分型,发现两个亚组之间存在显着的生存差异,上调的表达类型表现出免疫热表型。最后,实验结果证实了hub基因(NAA15)在EC中的表达。我们的研究结果表明,与细胞内芳香族化合物代谢途径相关的基因可用于 EC 的免疫治疗。© 2024。作者。
Endometrial cancer (EC) is associated with significant risk factors such as polycystic ovarian syndrome (PCOS) and sedentary behavior. In our study, we aim to employ machine learning algorithms to investigate the potential molecular processes that underlie their interaction and explore their respective roles in the diagnosis and immunotherapy of EC. The GEO database provides access to microarray data, which was utilized in this study to identify gene expression modules associated with PCOS and sedentary behavior, using weighted gene expression network analysis (WGCNA). Cluego software was then employed to investigate the energy enrichment of shared pathways in both PCOS and sedentary individuals, and differential gene analysis was used to confirm another two databases. The miRNAs-mRNAs controlled network was constructed to verify the pathway. The immune-related factors of the shared pathway in EC were then analyzed. Finally, to validate our findings, we conducted cell experiments using EC cell lines (AN3CA, KLE, Ishikawa, RL95-2, and HEC-1A). We found that increased intracellular aromatic compound anabolism is a common feature of both PCOS and sedentary individuals. We then developed a disease pathway model that was based on the common genetic characteristics of PCOS and sedentary behavior. We utilized pathway typing in EC samples and found a significant survival difference between the two subgroups, with the upregulated expression type exhibiting an immune-hot phenotype. Finally, the experimental results confirmed the expression of the hub gene (NAA15) in EC. The findings of our study suggest that genes related to the intracellular aromatic compound metabolic pathway can be used for immunotherapy of EC.© 2024. The Author(s).