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Updated: Jun 28, 2026

Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
Ankyrin repeat domain 1, ANKRD1, a novel determinant of cisplatin sensitivity expressed in ovarian cancer
Lyndee L Scurr1, Alexander D Guminski, Yoke-Eng Chiew
1Westmead Institute for Cancer Research, University of Sydney at the Westmead Millennium Institute, Westmead Hospital, Westmead, NSW, Australia.
Purpose:
The standard of care for ovarian cancer includes platinum-based chemotherapy. It is not possible, however, to predict clinical platinum sensitivity or to design rational strategies to overcome resistance. We used a novel approach to identify altered gene expression associated with high sensitivity to cisplatin, to define novel targets to sensitize tumor cells to platins and ultimately improve the effectiveness of this widely used class of chemotherapeutics.
Experimental Design:
Using differential display PCR, we identified genes differentially expressed in a mutagenized cell line with unusual sensitivity to cisplatin. The most highly differentially expressed gene was selected, and its role in determining cisplatin sensitivity was validated by gene transfection and small interfering RNA (siRNA) approaches, by association of expression levels with cisplatin sensitivity in cell lines, and by association of tumor expression levels with survival in a retrospective cohort of 71 patients with serous ovarian adenocarcinoma.
Results:
The most highly differently expressed gene identified was ANKRD1, ankyrin repeat domain 1 (cardiac muscle). ANKRD1 mRNA levels were correlated with platinum sensitivity in cell lines, and most significantly, decreasing ANKRD1 using siRNA increased cisplatin sensitivity >2-fold. ANKRD1 was expressed in the majority of ovarian adenocarcinomas tested (62/71, 87%), and higher tumor levels of ANKRD1 were found in patients with worse outcome (overall survival, P=0.013).
Conclusions:
These findings suggest that ANKRD1, a gene not previously associated with ovarian cancer or with response to chemotherapy, is associated with treatment outcome, and decreasing ANKRD1 expression, or function, is a potential strategy to sensitize tumors to platinum-based drugs.
Insights
Researchers identified ANKRD1 as a key gene influencing platinum sensitivity in ovarian cancer. Decreasing ANKRD1 expression may enhance chemotherapy effectiveness, offering a new strategy for treating this disease.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Platinum-based chemotherapy is standard for ovarian cancer but predicting sensitivity and overcoming resistance remains challenging.
- Identifying novel therapeutic targets is crucial for improving treatment outcomes in ovarian cancer.
Purpose of the Study:
- To identify genes associated with cisplatin sensitivity in ovarian cancer using a novel approach.
- To explore ANKRD1 as a potential therapeutic target for sensitizing ovarian tumors to platinum-based chemotherapy.
Main Methods:
- Differential display PCR was used to identify differentially expressed genes in cisplatin-sensitive cell lines.
- Gene transfection and siRNA were employed to validate the role of ANKRD1 in cisplatin sensitivity.
- Expression levels of ANKRD1 were correlated with patient survival in a cohort of ovarian adenocarcinoma patients.
Main Results:
- ANKRD1 (ankyrin repeat domain 1) was identified as the most highly differentially expressed gene.
- ANKRD1 mRNA levels correlated with platinum sensitivity; siRNA-mediated knockdown increased cisplatin sensitivity over twofold.
- ANKRD1 was expressed in 87% of ovarian adenocarcinomas, with higher levels associated with poorer patient survival.
Conclusions:
- ANKRD1 is a novel gene associated with ovarian cancer treatment outcome and platinum response.
- Targeting ANKRD1 expression or function presents a potential strategy to sensitize ovarian tumors to platinum-based chemotherapy.
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