早发性和晚发性卵巢癌的分子特征：来自多维证据的见解。

IF 4.2 3区医学 Q1 REPRODUCTIVE BIOLOGY

Journal of Ovarian Research Pub Date : 2025-04-23 DOI:10.1186/s13048-025-01664-9

Yanting Shen, Jie Cheng, Qing Ding, Zhihui Tao

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引用次数: 0

摘要

背景：卵巢癌（OC）是最致命的妇科恶性肿瘤之一，其特点是预后差。虽然衰老是一个公认的风险因素，但区分早发性和晚发性卵巢癌的潜在机制仍然知之甚少。方法：本研究使用GBD数据库分析全球卵巢癌负担和年龄相关趋势。研究采用55岁的截止年龄来区分早发性和晚发性卵巢癌，并采用孟德尔随机化方法来研究年龄与卵巢癌之间的因果关系。机器学习应用于识别肿瘤特异性年龄相关基因，随后进行生物信息学分析和单细胞测序，以探索这些基因和免疫谱改变在卵巢癌中的作用。此外，还构建了模型，并进行了药物敏感性分析，以评估其作为诊断标志物或治疗靶点的潜力。结果：卵巢癌的发病率和死亡率呈现出与年龄相关的趋势，端粒长度与风险增加呈正相关（OR = 1.27, 95% CI: 1.01-1.60, P = 3.90 × 10⁻2）。老年OC患者预后较差。PRKCD和UCP2在卵巢癌中显著上调。PRKCD促进上皮-间质转化（EMT），促进卵巢癌进展，而UCP2调节ROS动力学，影响化疗耐药。免疫微环境分析揭示了高表达组和低表达组之间的差异，特别是在T细胞、巨噬细胞和其他免疫细胞中。这两种基因都对多种药物敏感，包括达沙替尼、氟伐他汀，这突出了它们作为治疗靶点的潜力。结论：年龄是卵巢癌的重要危险因素，PRKCD和UCP2与卵巢癌的发生和发展密切相关。这些基因有望成为卵巢癌的新型生物标志物和治疗靶点。

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Molecular characteristics of early- and late-onset ovarian cancer: insights from multidimensional evidence.

Background: Ovarian cancer (OC) is among the most lethal gynecologic malignancies, characterized by poor prognosis. While aging is a well-established risk factor, the underlying mechanisms distinguishing early- and late-onset ovarian cancer remain poorly understood.

Methods: This study analyzed the global burden and age-related trends of ovarian cancer using the GBD database. A cut-off age of 55 years was used to differentiate between early and late onset ovarian cancer, and a Mendelian randomization method was also used to investigate the causal relationship between aging and ovarian cancer. Machine learning was applied to identify tumor-specific age-associated genes, followed by bioinformatics analyses and single-cell sequencing to explore the roles of these genes and immune profile alterations in ovarian cancer. Additionally, models were constructed, and drug sensitivity analyses performed to evaluate their potential as diagnostic markers or therapeutic targets.

Results: Ovarian cancer incidence and mortality exhibit age-related trends, with telomere length positively associated with increased risk (OR = 1.27, 95% CI: 1.01-1.60, P = 3.90 × 10⁻²). Older patients with OC have a worse prognosis. PRKCD and UCP2 were significantly upregulated in ovarian cancer. PRKCD facilitates epithelial-mesenchymal transition (EMT), contributing to ovarian cancer progression, while UCP2 modulates ROS dynamics, influencing chemoresistance. Immune microenvironment analysis revealed differences between high- and low-expression groups, particularly in T cells, macrophages, and other immune cells. Both genes are sensitive to a varity of drugs, including dasatinib, fluvastatin, highlighting their potential as therapeutic targets.

Conclusion: Aging is a significant risk factor for ovarian cancer, with PRKCD and UCP2 closely linked to its onset and progression. These genes show promise as novel biomarkers and therapeutic targets for ovarian cancer.

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来源期刊

Journal of Ovarian Research REPRODUCTIVE BIOLOGY-

CiteScore

6.20

自引率

2.50%

发文量

125

审稿时长

>12 weeks

期刊介绍： Journal of Ovarian Research is an open access, peer reviewed, online journal that aims to provide a forum for high-quality basic and clinical research on ovarian function, abnormalities, and cancer. The journal focuses on research that provides new insights into ovarian functions as well as prevention and treatment of diseases afflicting the organ. Topical areas include, but are not restricted to: Ovary development, hormone secretion and regulation Follicle growth and ovulation Infertility and Polycystic ovarian syndrome Regulation of pituitary and other biological functions by ovarian hormones Ovarian cancer, its prevention, diagnosis and treatment Drug development and screening Role of stem cells in ovary development and function.