PLAC1 is an independent predictor of poor survival, and promotes cell proliferation and invasion in cervical cancer

Mol Med Rep. 2021 Nov;24(5):800. doi: 10.3892/mmr.2021.12440. Epub 2021 Sep 15.

Abstract

Placenta‑specific protein 1 (PLAC1) is inversely associated with survival in several types of cancer. However, whether PLAC1 is involved in the progression of cervical cancer (CC) remains to be elucidated. Therefore, the present study aimed to evaluate the prognostic role of PLAC1 in CC by determining the relationship between clinicopathological factors, PLAC1 gene expression and survival prognosis using univariate and multivariate Cox proportional‑hazards regression analyses. Similarly, Kaplan‑Meier curves were evaluated with the log‑rank test. Subsequently, gene set enrichment analysis was performed to compare the high‑ and low‑PLAC1 expression phenotypes. Functional studies were further conducted in PLAC1‑overexpressing HeLa cells and PLAC1‑silenced MS751 cells, and western blotting was performed to determine whether PLAC1 promoted CC progression via epithelial‑mesenchymal transition (EMT). The findings demonstrated that high expression of PLAC1 was associated with American Joint Committee on Cancer metastasis pathological score and suggested a poor overall survival. 'mTOR complex 1 signaling', 'interferon α response' and 'hypoxia' were differentially enriched in the high‑PLAC1 phenotype. Furthermore, PLAC1 promoted the invasion of CC cells in vitro. E‑cadherin expression was decreased in the PLAC1‑overexpressing cells, accompanied by increased expression of the mesenchymal markers, Vimentin, MMP2 and Slug, and the opposite effects were observed in PLAC1‑silenced cells. Taken together, the present results indicated that high expression of PLAC1 was associated with poor survival and PLAC1 promoted metastasis via EMT in CC.

Keywords: cervical cancer; epithelial‑mesenchymal transition; placenta‑specific protein 1; prognosis; tumor metastasis.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Databases, Genetic
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • HeLa Cells
  • Humans
  • Kaplan-Meier Estimate
  • Neoplasm Invasiveness / genetics
  • Pregnancy Proteins / genetics*
  • Pregnancy Proteins / metabolism
  • Prognosis
  • Proportional Hazards Models
  • Signal Transduction / genetics
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology

Substances

  • PLAC1 protein, human
  • Pregnancy Proteins

Grants and funding

The project was supported by Health Profession Clinical Research Funds of Shanghai Municipal Health Commission (grant no. 20194Y0259), Natural Science Research Funds of Minhang District, Shanghai (grant no. 2019MHZ038) and Key Medical Specialty funded by Shanghai Fifth People's Hospital, Fudan University (grant no. 2020WYZDZK13)