CDS2 Drives Tumor Progression in Epithelial Ovarian Cancer via the PI3K/AKT Pathway.
5 affiliations
- 1Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China.
- 2Department of Gynecology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
- 3The First School of Clinical Medicine, Guangdong Medical University, Zhanjiang, Guangdong, China.
- 4School of Obstetrics and Pediatrics, Guangdong Medical University, Zhanjiang, Guangdong, China.
- 5Department of Biology, School of Basic Medical Sciences, Guangdong Medical University, Zhanjiang, Guangdong, China.
Abstract
Background
Epithelial ovarian cancer (EOC) frequently disseminates within the lipid-rich peritoneal cavity, where tumor progression is accompanied by metabolic adaptations involving lipid utilization and mitochondrial function. Although these metabolic alterations are increasingly recognized as important features of EOC progression and peritoneal metastasis, the molecular factors linking mitochondrial-lipid metabolic remodeling with aggressive tumor behavior remain incompletely characterized. We therefore integrated mitochondrial- and lipid metabolism-related transcriptomic analyses to identify candidate regulators and further investigated the clinical and biological features associated with CDS2.Results
Seven key genes associated with mitochondrial and lipid metabolism were identified in EOC through comprehensive bioinformatic analyses and were used to construct the MALRS prognostic model. Further integration of FIGO stage, histologic grade, and MALRS scores yielded a nomogram whose calibration plots showed good agreement between predicted and observed 1-, 3-, and 5-year survival probabilities. Subsequent screening of these candidate genes in chemotherapy-resistant datasets identified CDP-diacylglycerol synthase 2 (CDS2) as the most consistently upregulated candidate gene. Clinical validation confirmed that CDS2 was significantly overexpressed in tumor tissues and was associated with advanced disease stage, and survival analysis showed that higher CDS2 expression was associated with shorter progression-free survival (PFS) in stage III/IV patients. Functional characterization demonstrated that CDS2 overexpression promoted both lipid droplet accumulation and migratory capacity in ovarian cancer cells. Pathway analysis identified significant enrichment of PI3K/AKT signaling, and experimental validation confirmed CDS2-mediated hyperactivation of PI3K/AKT phosphorylation. Computational immune-deconvolution analyses further identified exploratory associations between CDS2 expression, estimated T-cell abundance, and immune-checkpoint transcripts.Conclusion
CDS2 is a lipid metabolism-associated candidate biomarker linked to aggressive clinicopathological features in EOC. Our findings associate CDS2 with disease progression, PI3K/AKT-related signaling, and immune-related transcriptomic features, supporting its further evaluation as a candidate prognostic marker.
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BibTeX
@article{cao2026cds2,
title = {{CDS2 Drives Tumor Progression in Epithelial Ovarian Cancer via the PI3K/AKT Pathway.}},
author = {Lixue Cao and Yanzhen Chen and Yingqi Liu and Changnian Yang and Zhentao Zhang and Yongqing Lin and Yiyuan Wang and Siman Chen and Fei Yu and Haiyan Ye and Shanshan Wu},
journal = {Cancer medicine},
year = {2026},
month = oct,
doi = {10.1002/cam4.72309},
url = {https://europepmc.org/article/MED/42897435},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - CDS2 Drives Tumor Progression in Epithelial Ovarian Cancer via the PI3K/AKT Pathway.
AU - Lixue Cao
AU - Yanzhen Chen
AU - Yingqi Liu
AU - Changnian Yang
AU - Zhentao Zhang
AU - Yongqing Lin
AU - Yiyuan Wang
AU - Siman Chen
AU - Fei Yu
AU - Haiyan Ye
AU - Shanshan Wu
PY - 2026
DA - 2026/10/01
JO - Cancer medicine
DO - 10.1002/cam4.72309
UR - https://europepmc.org/article/MED/42897435
AB - Background Epithelial ovarian cancer (EOC) frequently disseminates within the lipid-rich peritoneal cavity, where tumor progression is accompanied by metabolic adaptations involving lipid utilization and mitochondrial function. Although these metabolic alterations are increasingly recognized as important features of EOC progression and peritoneal metastasis, the molecular factors linking mitochondrial-lipid metabolic remodeling with aggressive tumor behavior remain incompletely characterized. We therefore integrated mitochondrial- and lipid metabolism-related transcriptomic analyses to identify candidate regulators and further investigated the clinical and biological features associated with CDS2.Results Seven key genes associated with mitochondrial and lipid metabolism were identified in EOC through comprehensive bioinformatic analyses and were used to construct the MALRS prognostic model. Further integration of FIGO stage, histologic grade, and MALRS scores yielded a nomogram whose calibration plots showed good agreement between predicted and observed 1-, 3-, and 5-year survival probabilities. Subsequent screening of these candidate genes in chemotherapy-resistant datasets identified CDP-diacylglycerol synthase 2 (CDS2) as the most consistently upregulated candidate gene. Clinical validation confirmed that CDS2 was significantly overexpressed in tumor tissues and was associated with advanced disease stage, and survival analysis showed that higher CDS2 expression was associated with shorter progression-free survival (PFS) in stage III/IV patients. Functional characterization demonstrated that CDS2 overexpression promoted both lipid droplet accumulation and migratory capacity in ovarian cancer cells. Pathway analysis identified significant enrichment of PI3K/AKT signaling, and experimental validation confirmed CDS2-mediated hyperactivation of PI3K/AKT phosphorylation. Computational immune-deconvolution analyses further identified exploratory associations between CDS2 expression, estimated T-cell abundance, and immune-checkpoint transcripts.Conclusion CDS2 is a lipid metabolism-associated candidate biomarker linked to aggressive clinicopathological features in EOC. Our findings associate CDS2 with disease progression, PI3K/AKT-related signaling, and immune-related transcriptomic features, supporting its further evaluation as a candidate prognostic marker.
SN - 2045-7634
ER -