journal article·2026-07-17Open access

Multi‐Omics Profiling of High‐Grade Serous Ovarian Cancer Reveals an Inflammation‐Related Lipid Metabolism Subtype Associated With Platinum Resistance

Yuxi Zhao, Junyi Li, Bo Zheng, Wanshan Liu, Yaru Wang, Shufeng Wang, Ying Cui, Huiqin Guo, Hongxia Wang, Ting Xiao, Kun Qian, Jing Zuo

Abstract

ABSTRACT Ovarian cancer is the deadliest gynecological malignancy. The main obstacle in treating high‐grade serous ovarian cancer (HGSOC) is platinum resistance. The mechanistic interface between tumor metabolic reprogramming and platinum resistance remains undefined. We integrated proteomic and metabolomic profiling of 97 primary HGSOC tumors to map the molecular landscape. Unsupervised clustering identified three subtypes. Subtype 3 exhibited a higher platinum resistance rate (64.5%), as well as worse overall ( p = 0.001) and recurrence‐free ( p = 0.0001) survival. At the molecular level, both Subtypes 2 and 3 tumors displayed phenotypes of activated lipid metabolism. However, Subtype 3 tumors were unique, exhibiting potential divergence between lipid metabolism and bioenergetics. The arachidonic acid metabolism pathway was upregulated ( p = 2.0 × 10 −6 ), and the key enzyme cyclooxygenase‐2 (COX‐2) was overexpressed ( p < 0.001). Subtype 3 tumors exhibited an inflammation‐associated state with the highest infiltration of M2‐like macrophages ( p = 0.007). Single‐cell transcriptomics revealed increased expression of PTGS2 (encoding COX‐2, p = 0.001) and CD163 ( p < 2.2 × 10 −16 ) in macrophages from platinum‐resistant HGSOC. Multiplex immunofluorescence confirmed that platinum‐resistant tumors had a higher proportion of COX‐2 + cells in M2‐like macrophages ( p = 0.010). These findings define a high‐risk HGSOC subtype characterized by inflammation‐related lipid metabolism. This suggests targeting the arachidonic acid metabolism pathway as a way to overcome platinum resistance.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Cancer, Lipids, and Metabolism · Ferroptosis and cancer prognosis · Immune cells in cancer

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Gynecologic Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China

State Key Laboratory of Molecular Oncology Department of Etiology and Carcinogenesis National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China

Department of Pathology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China

State Key Laboratory of Systems Medicine for Cancer School of Biomedical Engineering Institute of Medical Robotics and Shanghai Academy of Experimental Medicine Shanghai Jiao Tong University Shanghai China

State Key Laboratory for Oncogenes and Related Genes Shanghai Key Laboratory of Gynecologic Oncology Shanghai China

Department of Clinical Trial Research Center Beijing Hospital National Center of Gerontology Institute of Geriatric Medicine Chinese Academy of Medical Sciences Beijing China

National Center of Biomedical Analysis Beijing China

Institute of Mass Spectrometry Zhejiang Engineering Research Center of Advanced Mass Spectrometry and Clinical Application School of Material Science and Chemical Engineering Ningbo University Ningbo China

Zhenhai Institute of Mass Spectrometry Ningbo China

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China

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