Abstract 2941: Functional proteomic aberrations post-chemotherapy with paclitaxel and carboplatin in patients with advanced ovarian cancer
Authors: Sanghoon Lee, Li Zhao, Joseph Celestino, Kelly M. Rangel, Richard A. Hajek, Mark S. Kim, Sara E. Sharafi, Jinsong Liu, Nicole D. Fleming, Karen H. Lu, Jianhua Zhang, P. Andrew Futreal, Gordon B. Mills, Shannon N. Westin, Anil K. Sood, Amir A. Jazaeri, Robert L. Coleman
Journal: Cancer Research (2020)

Abstract Background: High-grade serous ovarian cancer (HGSOC) remains the leading cause of death from gynecologic malignancies. Here, we examined tumoral proteome changes following neoadjuvant chemotherapy (NACT) to identify potential predictive and prognostic biomarkers of response to primary chemotherapy. Methods: A total of 65 tissue specimens from 10 patients with advanced-stage HGSOC were collected from matched pre- and post-NACT (3 cycles of dose-dense paclitaxel and carboplatin). Protein expression was assessed using reverse-phase protein arrays (RPPA). All relative protein levels using 297 antibodies were normalized by the expression level of pre-treatment samples, and then protein expression alterations and functional analyses were performed by Reactome pathway analysis followed by statistical analysis. Results: The protein expression patterns of samples tended to cluster according to the time point (pre- and post-treatment) by a non-supervised clustering analysis using all the proteins assessed in the RPPA panel. Five differentially expressed proteins among 239 proteins (adj. p&amp;lt;0.1, log2FC≥1) were identified by RPPA. We identified XBP1, MYH11, and S100A4 as being upregulated and CCNB1 and TFRC were down-regulated post-treatment compared to pre-treatment. We also observed significant enrichment of specific functional and signaling pathways by pathway analysis; these included PI3K/AKT signaling, necrosis and programmed cell death (upregulated, p&amp;lt;0.05, FDR&amp;lt;1), and cell cycle and homology-directed repair (HDR) through homologous recombination repair and G2/M checkpoints (down-regulated, p&amp;lt;0.02, FDR&amp;lt;0.5) in post-treatment compared to pre-treatment. Interestingly, cell cycle, DNA damage, and G2 checkpoint pathways at post-treatment exhibited significantly lower pathway scores than pre-treatment. Conclusion: Our findings identified significant proteomic alterations following NACT, and could provide insights into interval proteomic alterations following induction chemotherapy in advanced-stage ovarian cancer patients. These data present information to optimize future clinical trial designs for patients with ovarian cancer. Citation Format: Sanghoon Lee, Li Zhao, Joseph Celestino, Kelly M. Rangel, Richard A. Hajek, Mark S. Kim, Sara E. Sharafi, Jinsong Liu, Nicole D. Fleming, Karen H. Lu, Jianhua Zhang, P. Andrew Futreal, Gordon B. Mills, Shannon N. Westin, Anil K. Sood, Amir A. Jazaeri, Robert L. Coleman. Functional proteomic aberrations post-chemotherapy with paclitaxel and carboplatin in patients with advanced ovarian cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2941.