多组学泛癌症分析揭示了 PPA2 的预后价值和免疫功能,重点关注乳腺癌。
Multi-omics pan-cancer analysis reveals the prognostic values and immunological functions of PPA2, with a spotlight on breast cancer.
发表日期:2024
作者:
Jia-Ning Zhang, Bei-Bei Yang, Lin-Wei Li, Hao Xu, Bin Wang, Zi-Lu Yi, Xi-Rui Zhou, Hong Liu
来源:
Frontiers in Immunology
摘要:
最近,无机焦磷酸酶 2 (PPA2) 在许多肿瘤中的作用仅停留在表面。因此,我们的目的是分析PPA2在泛癌中的潜在功能,重点关注其在乳腺癌中的作用。主要利用TCGA和GTEx等各种开放数据库进行系统的泛癌分析。我们探索了 PPA2 的临床价值以及各种生物学功能,包括表达水平和亚细胞定位、多维免疫相关分析、共表达网络和基因异质性。此外,我们不仅通过细胞实验验证了PPA2的功能,还分析了单细胞水平的PPA2及其药物敏感性。PPA2在多种肿瘤中异常表达,主要分布在线粒体中。此外,分析指标(OS、DSS、DFI和PFI)提示PPA2具有显着的预后价值。同时分析了PPA2在泛癌中的基因组异质性(包括TMB、MSI、MATH和NEO)。在多个肿瘤中,结果显示 PPA2 表达水平与不同免疫特征(例如免疫细胞浸润)之间存在密切相关性。所有这些都表明PPA2有可能应用于指导免疫治疗。我们还证明PPA2促进了乳腺癌的进程。最后,一些针对PPA2异常表达的潜在治疗药物(如氟维司群)被揭示。 总之,结果证明了PPA2在泛癌研究中的巨大价值,以及其作为乳腺肿瘤治疗靶点的潜力。版权所有 © 2024 张、杨、李、徐、王、易、周、刘。
Recently, the role of inorganic pyrophosphatase 2 (PPA2) has been remaining merely superficial in many tumors. Hence, the aim was to analyze the potential functions of PPA2 in pan-cancer, focusing on its role in breast cancer.A systematic pan-cancer analysis conducted primarily utilizing various open databases such as TCGA and GTEx. We explored the clinical value of PPA2 as well as various biological functions, including expression levels and subcellular localization, multi-dimensional immune-correlation analysis, co-expression networks, and gene heterogeneity. In addition, we not only verified the function of PPA2 through cell experiments but also analyzed PPA2 at the single-cell level and its drug sensitivity.PPA2 is abnormally expressed in various tumors, and it is mainly distributed in mitochondria. Furthermore, the indicators (OS, DSS, DFI, and PFI) of analysis hint that PPA2 exhibits significant prognostic value. At the same time, the genomic heterogeneity (including TMB, MSI, MATH, and NEO) of PPA2 in pan-cancer was analyzed. Across multiple tumors, the results showed a close correlation between PPA2 expression levels and different immune signatures (such as immune cell infiltration). All of these indicate that PPA2 could potentially be applied in the guidance of immunotherapy. We also have demonstrated that PPA2 promoted the process of breast cancer. Finally, some potential therapeutic agents (such as Fulvestrant) targeting the abnormal expression of PPA2 are revealed.In conclusion, the results demonstrated the great value of PPA2 in pan-cancer research, as well as its potential as a therapeutic target for breast tumors.Copyright © 2024 Zhang, Yang, Li, Xu, Wang, Yi, Zhou and Liu.