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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1524606
This article is part of the Research Topic Renewed Insight into Cancer Mechanism and Therapy View all 5 articles

Implication of Fibroblast Growth Factor 7 in Ovarian Cancer Metastases and Patient Survival

Provisionally accepted
Laura Mortan Laura Mortan Brooke A Meelheim Brooke A Meelheim Justin Garland Justin Garland Jacqueline A Bohn Jacqueline A Bohn Zitha Redempta Isingizwe Zitha Redempta Isingizwe Doris Mangiaracina Benbrook Doris Mangiaracina Benbrook *
  • University of Oklahoma Health Sciences Center, Oklahoma City, United States

The final, formatted version of the article will be published soon.

    Background/Objectives: Patients with ovarian cancer commonly experience metastases and recurrences, which contribute to high mortality. Our objective was to better understand ovarian cancer metastasis and identify candidate biomarkers and drug targets for predicting and pre-venting ovarian cancer recurrence.Methods: Transcripts of 770 cancer-associated genes were compared in cells collected from ascitic fluid versus resected tumors of an ES-2 orthotopic ovarian cancer mouse model. Associated cell types and pathways were explored with bioinformatics. FGF7 protein was measured using capillarybased immunoassays or ELISA in mouse and clinical specimens. Significances of differential gene expression and patient prognosis were determined by volcano plot and the log-rank test, respectively. Results: Tumor transcriptomes exhibited higher endothelial cells, oxygenation, proteasome activity and metabolism in comparison to ascites, but similar percentages of cancer-associated fibroblasts and immune cells. FGF7 mRNA was significantly higher in mouse tumors compared to ascites. FGF7 protein was significantly higher in tumors than in ascites in independent mouse models and clinical specimens. Serum FGF7 protein levels above the median of 25 patients with ovarian cancer were associated with worse progression-free and overall survival (p=0.005 and 0.019, respectively), independent of patient and tumor characteristics.Conclusions: In comparison to ascites, tumors exhibit different transcriptomic profiles that identify candidate biomarkers and drug targets for predicting and preventing recurrence. Among these, elevated tumoral FGF7 validated at the protein level and elevated serum FGF7 was significantly associated with worse patient survival. These result supports further development of FGF7 receptortargeted drugs and serum FGF7 to prevent and predict recurrence, respectively.

    Keywords: Cancer, metastases, Ascites, Fibroblast Growth Factor 7, FGF7, Survival Font: Italic Font: Italic, Superscript Font: Italic Formatted: Font: Times New Roman, 12 pt Font: Italic Formatted: Superscript Formatted: Font: Times New Roman

    Received: 07 Nov 2024; Accepted: 23 Dec 2024.

    Copyright: © 2024 Mortan, Meelheim, Garland, Bohn, Isingizwe and Benbrook. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Doris Mangiaracina Benbrook, University of Oklahoma Health Sciences Center, Oklahoma City, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.