Integrative transcriptome analyses of the human fallopian tube: Fimbria and ampulla—site of origin of serous carcinoma of the ovary

Ramlogan Sowamber, Omar Nelson, Leah Dodds, Victoria Decastro, Iru Paudel, Anca Milea, Michael Considine, Leslie Cope, Andre Pinto, Matthew Schlumbrecht, Brian Slomovitz, Patricia A. Shaw, Sophia H.L. George

Research output: Contribution to journalArticlepeer-review

Abstract

Epithelial ovarian cancer represents a group of heterogeneous diseases with high grade serous cancer (HGSC) representing the most common histotype. Molecular profiles of precancerous lesions found in the fallopian tube have implicated this tissue as the presumptive site of origin of HGSC. Precancerous lesions are primarily found in the distal fallopian tube (fimbria), near the ovary relative to the proximal tissue (ampulla), nearer to the uterus. The proximity of the fimbria to the ovary and the link between ovulation, through follicular fluid release, and ovarian cancer risk led us to examine transcriptional responses of fallopian tube epithelia (FTE) at the different anatomical sites of the human fallopian tube. Gene expression profiles of matched FTE from the fimbria and from premenopausal women resulted in differentially expressed genes (DEGs): CYYR1, SALL1, FOXP2, TAAR1, AKR1C2/C3/C4, NMBR, ME1 and GSTA2. These genes are part of the antioxidant, stem and inflammation pathways. Comparisons between the luteal phase (post-ovulation) to the follicular phase (pre-ovulation) demonstrated greater differences in DEGs than a comparison between fimbria and fallopian tube anatomical differences alone. This data suggests that cyclical transcriptional changes experienced in pre-menopause are inherent physiological triggers that expose the FTE in the fimbria to cytotoxic stressors. These cyclical exposures induce transcriptional changes reflective of genotoxic and cytotoxic damage to the FTE in the fimbria which are closely related to transcriptional and genomic alterations observed in ovarian cancer.

Original languageEnglish (US)
Article number1090
JournalCancers
Volume12
Issue number5
DOIs
StatePublished - May 2020

Keywords

  • Ampulla
  • Differentially expressed genes (DEGs)
  • Fallopian tube
  • Fimbria
  • Laser capture microdissection
  • Ovarian cancer
  • Transcriptomic analysis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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