Comprehensive analysis of PPPCs family reveals the clinical significance of PPP1CA and PPP4C in breast cancer

Bioengineered. 2022 Jan;13(1):190-205. doi: 10.1080/21655979.2021.2012316.

Abstract

The phosphoprotein phosphatase catalytic subunit (PPPCs) family has been shown to play an important role in the development and progression of various malignancies, but its expression patterns and biological functions in breast cancer (BC) remain unclear. Therefore, we aimed to investigate the clinical significance and biological functions of the PPPCs family to understand its possible significance in the diagnosis, prognosis and treatment of breast cancer. We comprehensively investigated the expression levels, diagnostic accuracy, prognostic outcomes, biological functions and effects on immune cell infiltration of the PPPCs family in breast cancer using online databases. Except for PPP1CB, PPP1CC, PPP5C and PPEF1, the mRNA expression levels of the PPPCs family in breast cancer tissues were significantly different from those in paracancerous tissues. The differentially expressed genes (DEGs) were associated with the clinicopathological parameters and prognosis of breast cancer. The DEGs were mainly associated with the WNT signaling pathway, antigen presentation and DNA repair. In addition, the DEGs significantly affected the infiltration of immune cells in breast cancer tissues. Among the PPPCs family, PPP1CA and PPP4C played a prominent role in the progression of breast cancer, and inhibition of PPP1CA and PPP4C expression by siRNA can significantly inhibit breast cancer cells proliferation and migration. In conclusion, the PPPCs family, especially PPP1CA and PPP4C, could be used as new biomarkers to improve diagnostic accuracy, predict prognosis and novel targets for the treatment of breast cancer.

Keywords: Breast cancer; biomarker; diagnostic value; molecular function; phosphoprotein phosphatase catalytic subunit (PPPCs) family; prognostic value.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Databases, Genetic
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MCF-7 Cells
  • Phosphoprotein Phosphatases / genetics*
  • Phosphoprotein Phosphatases / metabolism*
  • Prognosis
  • Protein Phosphatase 1 / genetics*
  • Protein Phosphatase 1 / metabolism*
  • Survival Analysis
  • Up-Regulation*

Substances

  • Biomarkers, Tumor
  • PPP1CA protein, human
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 1
  • protein phosphatase 4

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China [Grant Nos. 81872169, 82172821, 82103386], Tianjin Key Research and Development Program Science and Technology Support Key Projects [Grant No. 17YFZCSY00690], Tianjin Municipal Science and Technology Project [Grant No. 19JCYBJC27400], Beijing-Tianjin-Hebei Basic Research Cooperation Project [Grant No. 20JCZXJC00120], Startup Fund for Scientific Research, Fujian Medical University [Grant No. 2019QH1157] and Chongqing Shapingba District Think Tank Research Project [Grant No. 2021SPBKXKT29].