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Reduced Gonadotrophin Receptor Expression Is Associated with a More Aggressive Ovarian Cancer Phenotype

Janelle Cheung1, Noor A Lokman1, Riya D Abraham1

  • 1Adelaide Medical School, Robinson Research Institute, University of Adelaide, Adelaide, SA 5000, Australia.

International Journal of Molecular Sciences
|December 30, 2020
PubMed

Insights

Lower expression of follicle-stimulating hormone receptor (FSHR) and luteinising hormone receptor (LHCGR) is linked to aggressive ovarian cancer and increased metastasis. Higher expression of these receptors correlates with better patient survival outcomes.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Follicle-stimulating hormone (FSH) and luteinising hormone (LH) are crucial for ovarian function.
  • The roles of FSH and LH receptors (FSHR, LHCGR) in ovarian cancer progression are not well understood.
  • Previous research has limited data on FSHR and LHCGR expression in ovarian cancer.

Purpose of the Study:

  • To investigate the impact of FSHR and LHCGR mRNA and protein expression on ovarian cancer progression.
  • To determine the functional role of FSHR and LHCGR in the pro-metastatic behavior of ovarian cancer cells.
  • To correlate receptor expression levels with patient survival outcomes.

Main Methods:

  • Analysis of publicly available databases for mRNA and protein expression.
  • Quantitative reverse transcription PCR (qRT-PCR) on ovarian cancer and benign tumor samples.
  • Immunohistochemistry on high-grade serous ovarian cancer (HGSOC) patient samples.
  • In vitro siRNA knockdown of FSHR and LHCGR in ovarian cancer cell lines.

Main Results:

  • High FSHR or LHCGR expression in ovarian cancer patients was associated with significantly longer progression-free survival (PFS) and overall survival (OS).
  • High FSHR protein expression correlated with improved PFS and OS.
  • Combined high expression of both FSHR and LHCGR indicated the best survival outcomes, while low expression of both predicted the poorest survival.
  • FSHR knockdown increased invasion in OVCAR3 and COV362 cells; LHCGR knockdown promoted invasion in COV362 cells.

Conclusions:

  • Lower expression of FSHR and LHCGR is linked to a more aggressive ovarian cancer phenotype.
  • Reduced FSHR and LHCGR expression promotes pro-metastatic behavior in ovarian cancer cells.
  • FSHR and LHCGR expression levels may serve as prognostic biomarkers for ovarian cancer.
Keywords:
FSHRLHCGRcancer progressiongonadotropinsovarian cancerserous ovarian cancer

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