PAX2 promotes epithelial ovarian cancer progression involving fatty acid metabolic reprogramming

Int J Oncol. 2020 Mar;56(3):697-708. doi: 10.3892/ijo.2020.4958. Epub 2020 Jan 10.

Abstract

Ovarian cancer is the fifth most common type of cancer afflicting women and frequently presents at a late stage with a poor prognosis. While paired box 2 (PAX2) expression is frequently lost in high‑grade serous ovarian cancer, it is expressed in a subset of ovarian tumors and may play a role in tumorigenesis. This study investigated the expression of PAX2 in ovarian cancer. The expression of PAX2 in a murine allograft model of ovarian cancer, the RM model, led to a more rapidly growing cell line both in vitro and in vivo. This finding was in accordance with the shorter progression‑free survival observed in patients with a higher PAX2 expression, as determined in this study cohort by immunohistochemistry. iTRAQ‑based proteomic profiling revealed that proteins involved in fatty acid metabolism and oxidative phosphorylation were found to be upregulated in RM tumors expressing PAX2. The expression of two key fatty acid metabolic genes was also found to be upregulated in PAX2‑expressing human ovarian cancer samples. The analysis of existing datasets also indicated that a high expression of key enzymes in fatty acid metabolism was associated with a shorter progression‑free survival time in patients with serous ovarian cancer. Thus, on the whole, the findings of this study indicate that PAX2 may promote ovarian cancer progression, involving fatty acid metabolic reprograming.

Keywords: ovarian cancer; fatty acid; paired box 2; proteomics; metabolic reprogramming.

MeSH terms

  • Animals
  • Carcinoma, Ovarian Epithelial / genetics
  • Carcinoma, Ovarian Epithelial / metabolism
  • Carcinoma, Ovarian Epithelial / mortality
  • Carcinoma, Ovarian Epithelial / pathology*
  • Cell Line
  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • Disease Progression
  • Fatty Acids / metabolism*
  • Female
  • Humans
  • Mice
  • Mice, SCID
  • Mitochondria / metabolism
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology*
  • Oxidative Phosphorylation
  • PAX2 Transcription Factor / genetics
  • PAX2 Transcription Factor / metabolism*
  • Prognosis
  • Progression-Free Survival

Substances

  • Fatty Acids
  • PAX2 Transcription Factor