Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Biomarker Development and Utilization in the Care of Women with Epithelial Ovarian Cancer

Taylor, Sarah Elizabeth (2023) Biomarker Development and Utilization in the Care of Women with Epithelial Ovarian Cancer. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

[img] PDF
Restricted to University of Pittsburgh users only until 12 April 2024.

Download (1MB) | Request a Copy


Epithelial ovarian cancer (EOC) has the third highest mortality:incidence ratio of all cancers, making it the deadliest of all gynecologic cancers and fifth leading cause of cancer death in women. These cancers have historically been grouped together as a single entity, and yet, are characterized by distinct histologic subtypes and molecular aberrations. Increasing knowledge regarding the distinct subtype biologic behavior has led to shifts in treatment paradigms. This work builds on the platform of knowledge that exists to better refine the biomarker development and utilization in this diverse disease.
In Project 1, we identified both clinicopathologic features as well as subsets of estrogen signaling related genes that are significantly associated with progression free (PFS) and overall survival (OS) for individuals with serous low malignant potential tumors and low grade serous ovarian cancers. This allowed us to build prediction models for recurrence, PFS and OS. In Project 2, our work demonstrates that employing a tumor testing first strategy for the identification of BRCA mutations is a cost-effective approach to improve testing rates that could be utilized at the time of initial diagnosis. Finally, in Project 3, we demonstrate that metformin impacts multiple facets of the tumor microenvironment. We find that metformin treatment is associated with a decrease in the presence of protumorigenic CA-MSCs in EOC. This is associated with a decrease in immune exclusion of T-cells, suggesting that metformin, via reduction in CA-MSCs, could be leading to a more immune-permissive environment. Instead, because we find that metformin may act by preventing the reprogramming of local tissue MSCs into CA-MSCs, this suggests that metformin can be best used clinically as a preventative therapy and in patients with early-stage disease.
In conclusion, EOC is a heterogeneous disease. Biomarkers for both prognosis as well as prediction of response to therapy have the potential to help define and treat the various subtypes that exist, leading to more nuanced, personalized and improved outcomes. Through three distinct projects, this work illustrates the diversity that is epithelial ovarian cancer and offers new insights into the development of potential new biomarkers and novel utilization of existing biomarkers.


Social Networking:
Share |


Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Taylor, Sarah Elizabethtaylorse2@upmc.eduset570000000213851707
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairSwitzer,
Committee CoChairEdwards,
Committee MemberOesterreich,
Committee MemberSmith, Kennethsmitkj2@UPMC.EDU
Committee MemberBeumer,
Committee MemberBuckanovich,
Committee MemberAlthouse,
Date: 12 April 2023
Date Type: Publication
Defense Date: 26 July 2022
Approval Date: 12 April 2023
Submission Date: 11 August 2022
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 114
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Clinical and Translational Science
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: ovarian cancer, biomarkers, low grade serous, low malignant potential, estrogen signaling, genetic testing, cost effectiveness, metformin, tumor microenvironment
Date Deposited: 12 Apr 2023 18:47
Last Modified: 12 Apr 2023 18:47


Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item