Frontiers in Immunology (Aug 2024)

Multi-omics pan-cancer analysis reveals the prognostic values and immunological functions of PPA2, with a spotlight on breast cancer

  • Jia-Ning Zhang,
  • Jia-Ning Zhang,
  • Jia-Ning Zhang,
  • Bei-Bei Yang,
  • Bei-Bei Yang,
  • Bei-Bei Yang,
  • Lin-Wei Li,
  • Lin-Wei Li,
  • Lin-Wei Li,
  • Hao Xu,
  • Hao Xu,
  • Hao Xu,
  • Bin Wang,
  • Bin Wang,
  • Bin Wang,
  • Zi-Lu Yi,
  • Zi-Lu Yi,
  • Zi-Lu Yi,
  • Xi-Rui Zhou,
  • Xi-Rui Zhou,
  • Xi-Rui Zhou,
  • Hong Liu,
  • Hong Liu,
  • Hong Liu

DOI
https://doi.org/10.3389/fimmu.2024.1435502
Journal volume & issue
Vol. 15

Abstract

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BackgroundRecently, 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.MethodsA 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.ResultsPPA2 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.ConclusionIn 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.

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