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Updated: Feb 7, 2026
Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
Expression Analysis of Platinum Sensitive and Resistant Epithelial Ovarian Cancer Patient Samples Reveals New
K Veskimäe1, M Scaravilli2, W Niininen2
1Department of Obstetrics and Gynecology, Tampere University Hospital, Tampere, Finland.
Abstract:
Ovarian cancer has the highest mortality rate of all gynecologic malignancies. Identification of new biomarkers is highly needed due to its late diagnosis and high recurrence rate. The objective of this study was to identify mechanisms of therapy resistance and potential biomarkers by analyzing mRNA and protein expression from samples derived from patients with platinum-sensitive and -resistant ovarian cancer (total cohort n = 53). The data revealed new candidates for targeted therapies, such as GREB1 and ROR2. We showed that the development of platinum resistance correlated with upregulation of ROR2, whereas GREB1 was downregulated. Moreover, we demonstrated that high levels of ROR2 in platinum-resistant samples were associated with upregulation of Wnt5a, STAT3 and NF-kB levels, suggesting that a crosstalk between the non-canonical Wnt5a-ROR2 and STAT3/NF-kB signaling pathways. Upregulation of ROR2, Wnt5a, STAT3 and NF-kB was further detected in a platinum-resistant cell-line model. The results of the present study provided insight into molecular mechanisms associated with platinum resistance that could be further investigated to improve treatment strategies in this clinically challenging gynecological cancer.
Insights
Researchers identified new biomarkers for ovarian cancer therapy resistance. ROR2 upregulation is linked to platinum resistance, while GREB1 is downregulated, offering potential therapeutic targets.
Area of Science:
- Gynecologic Oncology
- Molecular Biology
- Cancer Biomarkers
Background:
- Ovarian cancer has a high mortality rate and late diagnosis.
- There is a critical need for novel biomarkers due to high recurrence rates.
- Understanding platinum resistance mechanisms is crucial for improving treatment.
Purpose of the Study:
- To identify mechanisms of therapy resistance in ovarian cancer.
- To discover potential biomarkers for platinum resistance.
- To analyze mRNA and protein expression in platinum-sensitive and -resistant ovarian cancer samples.
Main Methods:
- Analysis of mRNA and protein expression in patient-derived samples (n=53).
- Comparison of molecular profiles between platinum-sensitive and -resistant ovarian cancer.
- Validation in a platinum-resistant ovarian cancer cell-line model.
Main Results:
- Identified GREB1 and ROR2 as potential therapeutic targets.
- Found ROR2 is upregulated and GREB1 is downregulated in platinum-resistant ovarian cancer.
- Demonstrated association of ROR2 with Wnt5a, STAT3, and NF-kB upregulation in resistant samples.
- Observed crosstalk between Wnt5a-ROR2 and STAT3/NF-kB signaling pathways.
Conclusions:
- The study provides insights into molecular mechanisms of platinum resistance in ovarian cancer.
- ROR2, Wnt5a, STAT3, and NF-kB are implicated in platinum resistance.
- These findings could inform the development of improved ovarian cancer treatment strategies.
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