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Abstract High-grade serous ovarian cancer (HGSOC) remains the deadliest cancer of the female reproductive system. Among the many treatment alternatives, platinum-based therapies have been ubiquitous. However, even though initial response is favorable, most patients experience relapse and chemoresistance. Many studies have highlighted the role of epithelial-mesenchymal transition (EMT) in contributing to chemoresistance. In fact, the EMT transcription factor SNAI1 (Snail) has been associated with the development of aggressive disease. Nevertheless, further studies are necessary to understand the underlying mechanisms by which Snail contributes to recurrence and resistance. Thus, our goal is to develop a clinically relevant model of chemoresistance in which to study the transcriptional landscape and gene signatures related to EMT, platinum resistance, and recurrence in HGSOC. After acquisition and characterization of a HGSOC patient sample, cells were continuously exposed to increasing concentrations of cisplatin in vitro, until approximately a tenfold increase in IC-50 relative to parental cells was achieved. RNA-seq analysis comparing the patient-derived sensitive and resistant cell line pair identified over 4, 000 genes that were differentially expressed. Furthermore, gene expression was evaluated against a database of genes associated with platinum resistance, revealing 273 genes linked with mechanisms of apoptosis, extracellular matrix signaling, immune response, cancer stemness, EMT, among others. Additionally, we analyzed previously published chromatin immunoprecipitation-sequencing (ChIP-seq) studies for Snail to determine the potential mechanism of EMT-induced therapy resistance. Our results indicate that most of the genes associated with platinum resistance mechanisms were identified by more than two Snail ChIP-seq studies, indicating their potential for being regulated. Furthermore, to establish whether such genes could also be regulated in HGSOC, we compared our findings to ATAC-seq studies done in ovarian cancer cell lines. Data obtained from these analyses will be used in the future assessment of Snail’s direct regulation of these pathways and functions. Citation Format: Tise Suzuki, Wanqiu Chen, Charles Wang, Juli Unternaehrer. The transcriptional landscape of cisplatin resistance and its relationship with epithelial mesenchymal transition in ovarian cancer abstract. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84 (5 Suppl₂): Abstract nr A033.
Suzuki et al. (Mon,) studied this question.