The Second Surgical Department of Breast Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin, China.
The Second Surgical Department of Breast Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Front Immunol. 2024 Aug 8;15:1435502. doi: 10.3389/fimmu.2024.1435502. eCollection 2024.
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.
最近，无机焦磷酸酶 2（PPA2）在许多肿瘤中的作用仍仅仅停留在表面。因此，本研究旨在分析 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。我们探讨了 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、多维免疫相关性分析、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，还在单细胞水平上分析了 PPA2 及其药物敏感性。
PPA2 在各种肿瘤中异常表达，主要分布在线粒体中。此外，分析指标（OS、DSS、DFI 和 PFI）表明 PPA2 具有显著的预后价值。同时，分析了泛癌中 PPA2 的基因组异质性（包括 TMB、MSI、MATH 和 NEO）。在多种肿瘤中，PPA2 表达水平与不同免疫特征（如免疫细胞浸润）之间存在密切相关性。所有这些都表明 PPA2 可能在免疫治疗指导中具有应用潜力。我们还证明了 PPA2 促进了乳腺癌的发生。最后，揭示了一些针对 PPA2 异常表达的潜在治疗药物（如氟维司群）。
总之，研究结果表明 PPA2 在泛癌研究中具有重要价值，同时也可能成为乳腺癌的治疗靶点。
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