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Genomic and transcriptomic data reveal molecular differences between homologous recombination deficiency subgroups in Chinese ovarian cancer patients.

作者信息

Wang Hongxia, Zhao Wenhong, Zhou Wenhao, Wang Na, Li Yijie, Qin Kaiyun, Jia Jingde, Wang Jiaqian, Song Congcong, Yu Yu, Zhang Fenghua, Cui Xu, Zhao Lanlan, Luo Haitao, Zhang Zhengmao

机构信息

Department of Gynecology, Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China.

Shenzhen Engineering Center for Translational Medicine of Precision Cancer Immunodiagnosis and Therapy, YuceBio Technology Co., Ltd, Shenzhen, 518000, China.

出版信息

Hum Genomics. 2025 Aug 31;19(1):104. doi: 10.1186/s40246-025-00806-w.


DOI:10.1186/s40246-025-00806-w
PMID:40887624
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12398958/
Abstract

BACKGROUND: Ovarian cancer (OV) has the highest mortality rate among gynecological cancers and shows varied responses to chemotherapy combined with PARP inhibitors based on homologous recombination deficiency (HRD) subtypes. METHODS: This study enrolled 143 Chinese OV patients to determine the HRD score grouping threshold using genomic features, dividing patients into HRD-high and HRD-low groups. Multi-omics sequencing was conducted on 70 patients receiving adjuvant chemotherapy with PARP inhibitors. RESULTS: In this study, TP53 mutations enriched in the HRD-high group, while ARID1A, PIK3CA, and PTEN mutations were more common in the HRD-low group. HRD-high patients exhibited stronger immune activation, including elevated STAT1 expression, HLA signatures, and increased M1 macrophage infiltration, correlating with better prognosis. Additionally, peripheral blood analysis revealed higher bMSI and maxVAF levels in HRD-low patients compared to HRD-high patients, suggesting ctDNA as a potential tool for dynamic monitoring post-treatment. CONCLUSIONS: This study identified distinct molecular and immune profiles between HRD subgroups in Chinese ovarian cancer patients. Patients with HRD-high and STAT1 expression ≥ 74 suggests PARPi benefit.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/504f/12398958/0ee429cb7b55/40246_2025_806_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/504f/12398958/7a81fbb3272b/40246_2025_806_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/504f/12398958/00fe13215b1d/40246_2025_806_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/504f/12398958/10930559c380/40246_2025_806_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/504f/12398958/99bf8507a3e7/40246_2025_806_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/504f/12398958/0ee429cb7b55/40246_2025_806_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/504f/12398958/7a81fbb3272b/40246_2025_806_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/504f/12398958/00fe13215b1d/40246_2025_806_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/504f/12398958/10930559c380/40246_2025_806_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/504f/12398958/99bf8507a3e7/40246_2025_806_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/504f/12398958/0ee429cb7b55/40246_2025_806_Fig4_HTML.jpg

相似文献

[1]
Genomic and transcriptomic data reveal molecular differences between homologous recombination deficiency subgroups in Chinese ovarian cancer patients.

Hum Genomics. 2025-8-31

[2]
Olaparib as treatment for platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency: Phase 2 LIGHT study final overall survival analysis.

Cancer. 2025-1-15

[3]
Routine Tumor Testing for Homologous Recombination Deficiency in Patients With High Grade Epithelial Ovarian Cancer at a Statewide Gynecological Cancer Service in Western Australia: An Observational Study.

Cancer Rep (Hoboken). 2025-9

[4]
HRProfiler Detects Homologous Recombination Deficiency in Breast and Ovarian Cancers Using Whole-Genome and Whole-Exome Sequencing Data.

Cancer Res. 2025-5-6

[5]
Homologous recombination deficiency (HRD) tests for ovarian cancer: a multicenter French phase II study (HERO).

BMC Cancer. 2025-7-1

[6]
Development of a prognosis model for PARP inhibitor therapies based on multiple genomic alterations associated with homologous recombination deficiency in ovarian cancer.

Int J Gynecol Cancer. 2025-6-25

[7]
The Molecular Mechanisms of Actions, Effects, and Clinical Implications of PARP Inhibitors in Epithelial Ovarian Cancers: A Systematic Review.

Int J Mol Sci. 2022-7-23

[8]
Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer.

Cochrane Database Syst Rev. 2022-2-16

[9]
BRCA1 promoter methylation predicts PARPi response in ovarian cancer: insights from the KOMET study.

Clin Epigenetics. 2025-8-7

[10]
Treatment, outcomes, and resource utilization among patients with metastatic breast and advanced epithelial ovarian cancer, by BRCA1/2 and HRD status.

Oncologist. 2025-8-4

本文引用的文献

[1]
Molecular classification of ovarian high-grade serous/endometrioid carcinomas through multi-omics analysis: JGOG3025-TR2 study.

Br J Cancer. 2024-11

[2]
Cancer incidence and mortality in China, 2022.

J Natl Cancer Cent. 2024-2-2

[3]
Cancer incidence and mortality in China, 2016.

J Natl Cancer Cent. 2022-2-27

[4]
Phase IIa Study of PLX2853 in Gynecologic Cancers With Known ARID1A Mutation and Phase Ib/IIa Study of PLX2853/Carboplatin in Platinum-Resistant Epithelial Ovarian Cancer.

JCO Precis Oncol. 2023-9

[5]
Heterogeneity and treatment landscape of ovarian carcinoma.

Nat Rev Clin Oncol. 2023-12

[6]
Survival rate of ovarian cancer in Asian countries: a systematic review and meta-analysis.

BMC Cancer. 2023-6-16

[7]
Homologous recombination deficiency status predicts response to platinum-based chemotherapy in Chinese patients with high-grade serous ovarian carcinoma.

J Ovarian Res. 2023-3-15

[8]
Neoadjuvant therapy with immune checkpoint blockade, antiangiogenesis, and chemotherapy for locally advanced gastric cancer.

Nat Commun. 2023-1-3

[9]
Mutations in circulating tumor DNA detected in the postoperative period predict poor survival in patients with ovarian cancer.

Biomed J. 2023-10

[10]
Circulating tumor DNA monitoring for early recurrence detection in epithelial ovarian cancer.

Gynecol Oncol. 2022-11

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