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Updated: Aug 8, 2026

Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
DUSP5 contributes to platinum resistance in ovarian cancer: single-cell discovery and functional validation
Chengfeng Liu1, Wehua Li2, Tingjun Liao3
1Department of Oncology, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China.
Background:
Platinum-based chemotherapy remains the cornerstone of ovarian cancer treatment, yet acquired resistance severely limits efficacy. Because platinum agents can also influence immunogenic cell death and tumor microenvironment (TME) remodeling, clarifying cellular pharmacological mechanisms of sensitivity and resistance within the ovarian cancer tumor ecosystem is important for understanding therapeutic failure.
Methods:
We integrated single-cell RNA-seq from treatment-naïve and post-neoadjuvant chemotherapy ovarian tumors with bulk multi-omics cohorts to map epithelial tumor heterogeneity, transcriptional reprogramming, pathway activation, immune infiltration, and inferred cell-cell communication networks. DUSP5 was identified as a candidate regulator linked to stress-adaptive programs. Functional validation included qPCR, proliferation, migration, colony-formation, carboplatin dose-response, and xenograft assays following stable DUSP5 knockdown.
Results:
Single-cell analysis revealed chemotherapy-associated epithelial states with enhanced stress, EMT, hypoxia, and inflammatory signatures. Elevated DUSP5 expression correlated with MAPK/JAK-STAT/TGF-β signaling, myeloid/stromal infiltration, and clinical outcome differences in independent cohorts. DUSP5 depletion suppressed proliferation and migration, amplified carboplatin-induced MAPK transcriptional responses and pro-apoptotic signaling (BAX/PUMA upregulation, BCL2 downregulation), reduced IC50 values in both OVCAR8 and SKOV3 cells, and significantly inhibited xenograft tumor growth.
Conclusion:
DUSP5 may contribute to platinum response and resistance by linking tumor-intrinsic adaptive programs with TME-associated features in ovarian cancer. These findings support DUSP5 as a candidate biomarker and therapeutic target that warrants further mechanistic and clinical validation.
Insights
DUSP5 influences platinum response and resistance in ovarian cancer by linking tumor adaptation to the tumor microenvironment. This suggests DUSP5 is a potential biomarker and therapeutic target for improving chemotherapy efficacy.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Platinum-based chemotherapy is standard for ovarian cancer but faces acquired resistance.
- Understanding platinum resistance mechanisms, including tumor microenvironment (TME) interactions, is crucial for therapeutic success.
Purpose of the Study:
- To investigate the cellular and molecular mechanisms underlying platinum sensitivity and resistance in ovarian cancer.
- To identify key regulators of tumor adaptation and TME interactions in response to chemotherapy.
Main Methods:
- Integrated single-cell RNA-seq and bulk multi-omics data from ovarian tumors.
- Analyzed epithelial heterogeneity, transcriptional changes, immune infiltration, and cell-cell communication.
- Performed functional validation of DUSP5 using knockdown and various in vitro/in vivo assays.
Main Results:
- Chemotherapy induced epithelial states with stress, EMT, hypoxia, and inflammatory signatures.
- Elevated DUSP5 expression correlated with specific signaling pathways, immune infiltration, and clinical outcomes.
- DUSP5 depletion reduced tumor cell proliferation, migration, and enhanced carboplatin sensitivity, inhibiting xenograft growth.
Conclusions:
- DUSP5 links tumor-intrinsic adaptive programs to TME features, impacting platinum response and resistance in ovarian cancer.
- DUSP5 is a potential biomarker for predicting platinum response and a therapeutic target for overcoming resistance.
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