Signal Transduction Pathway Activity in High-Grade, Serous Ovarian Carcinoma Reveals a More Favorable Prognosis in Tumors with Low PI3K and High NF-κB Pathway Activity: A Novel Approach to a Long-Standing Enigma
Abstract
We investigated signal transduction pathway (STP) activity in high-grade serous ovarian carcinoma (HGSC) in relation to progression-free survival (PFS) and overall survival (OS). We made use of signal transduction pathway activity analysis (STA analysis), a novel method to quantify functional STP activity. Activity of the following pathways was measured: androgen receptor (AR), estrogen receptor (ER), phosphoinositide 3-kinase (PI3K), Hedgehog (Hh), Notch, nuclear factor-kappa B (NF-κB), transforming growth factor beta (TGF-β), and Wnt. We selected HGSC samples from publicly available datasets of ovarian cancer tissue, and used repeated k-means clustering to identify pathway activity clusters. PFS and OS of the clusters were analyzed. We used a subset of publicly available dataset GSE9891 (n = 140), where repeated k-means clustering based on PI3K and NF-κB pathway activity in HGSC samples resulted in two stable clusters. The cluster with low PI3K and high NF-κB pathway activity (n = 72) had a more favorable prognosis for both PFS (p = 0.004) and OS (p = 0.001) compared to the high-PI3K and low-NF-κB pathway activity cluster (n = 68). The low PI3K and high NF-κB pathway activity of the favorable prognosis cluster may indicate a more active immune response, while the high PI3K and low NF-κB pathway activity of the unfavorable prognosis cluster may indicate high cell division.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 18, 2020
- Source ID
- 10.3390/cancers12092660
Entities
People
- Anja Van De Stolpe
- David Bowtell
- Joanne De Hullu
- Jurgen Piek
- Laura Van Lieshout
- Phyllis Van Der Ploeg
Organizations
- Cancer Institute of New South Wales
- National Health and Medical Research Council
- United States Army Medical Research and Development Command