Related Experiment Video
Updated: Mar 3, 2026
Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
DNA methylation and Transcriptome Changes Associated with Cisplatin Resistance in Ovarian Cancer
Riikka J Lund1, Kaisa Huhtinen2, Jussi Salmi3
1Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland. riikka.lund@utu.fi.
Abstract:
High-grade serous ovarian cancer is the most common ovarian cancer type. Although the combination of surgery and platinum-taxane chemotherapy provide an effective treatment, drug resistance frequently occurs leading to poor outcome. In order to clarify the molecular mechanisms of drug resistance, the DNA methylation and transcriptomic changes, associated with the development of drug resistance in high-grade serous ovarian cancer, were examined from patient derived malignant ascites cells. In parallel with large-scale transcriptome changes, cisplatin resistance was associated with loss of hypermethylation at several CpG sites primarily localized in the intergenic regions of the genome. The transcriptome and CpG methylome changes in response to cisplatin treatment of both sensitive and resistant cells were minimal, indicating the importance of post-translational mechanisms in regulating death or survival of the cells. The response of resistant cells to high concentrations of cisplatin revealed transcriptomic changes in potential key drivers of drug resistance, such as KLF4. Among the strongest changes was also induction of IL6 in resistant cells and the expression was further increased in response to cisplatin. Also, several other components of IL6 signaling were affected, further supporting previous observations on its importance in malignant transformation and development of drug resistance in ovarian cancer.
Insights
Drug resistance in high-grade serous ovarian cancer is linked to DNA methylation changes and altered gene expression. Post-translational modifications and IL6 signaling are crucial in chemoresistance development.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- High-grade serous ovarian cancer (HGSOC) is the most prevalent type.
- Platinum-taxane chemotherapy is standard but often fails due to drug resistance, leading to poor patient outcomes.
Purpose of the Study:
- To investigate the molecular mechanisms, including DNA methylation and transcriptomic alterations, underlying cisplatin resistance in HGSOC.
- To identify key molecular players involved in the development of chemoresistance.
Main Methods:
- Analysis of DNA methylation and transcriptomic profiles from patient-derived malignant ascites cells (sensitive and resistant to cisplatin).
- Comparative analysis of gene expression and CpG methylation patterns between sensitive and resistant cells.
- Examination of cellular responses to high-dose cisplatin treatment in resistant cells.
Main Results:
- Cisplatin resistance was associated with hypomethylation at intergenic CpG sites, alongside significant transcriptome changes.
- Minimal transcriptomic and methylome alterations were observed upon cisplatin treatment in both sensitive and resistant cells, suggesting a role for post-translational modifications.
- Resistant cells showed transcriptomic changes in key drivers like KLF4 and significant induction of IL6, which was further upregulated by cisplatin.
- IL6 signaling pathway components were affected, highlighting its role in HGSOC chemoresistance.
Conclusions:
- Cisplatin resistance in HGSOC involves epigenetic modifications and significant transcriptomic shifts.
- Post-translational mechanisms appear critical in regulating cell survival during chemotherapy.
- IL6 signaling is implicated as a key driver in the development and progression of ovarian cancer drug resistance.
Related Concept Videos
02:56Treatment Resistant Cancers
01:37Epigenetic Regulation
X-chromosome...
01:46Epigenetic Regulation