A proteogenomic analysis of cervical cancer reveals therapeutic and biological insights

IF 14.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Nature Communications Pub Date : 2024-11-22 DOI:10.1038/s41467-024-53830-0
Jing Yu, Xiuqi Gui, Yunhao Zou, Qian Liu, Zhicheng Yang, Jusheng An, Xuan Guo, Kaihua Wang, Jiaming Guo, Manni Huang, Shuhan Zhou, Jing Zuo, Yimin Chen, Lu Deng, Guangwen Yuan, Ning Li, Yan Song, Jia Jia, Jia Zeng, Yuxi Zhao, Xianming Liu, Xiaoxian Du, Yansheng Liu, Pei Wang, Bing Zhang, Li Ding, Ana I. Robles, Henry Rodriguez, Hu Zhou, Zhen Shao, Lingying Wu, Daming Gao
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Abstract

Although the incidence of cervical cancer (CC) has been reduced in high-income countries due to human papillomavirus (HPV) vaccination and screening strategies, it remains a significant public health issue that poses a threat to women’s health in low-income countries. Here, we perform a comprehensive proteogenomic profiling of CC tumors obtained from 139 Chinese women. Integrated proteogenomic analysis links genetic aberrations to downstream pathogenesis-related pathways and reveals the landscape of HPV-associated multi-omic changes. EP300 is found to enhance the acetylation of FOSL2-K222, consequently accelerating the malignant proliferation of CC cells. Proteomic stratification identifies three patient subgroups with distinct features in prognosis, genetic alterations, immune infiltration, and post-translational modification regulations. PRKCB is further identified as a potential radioresponse-related biomarker of CC patients. This study provides a valuable public resource for researchers and clinicians to delve into the molecular basis of CC, to identify potential treatments and to ultimately advance clinical practice.

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宫颈癌蛋白质基因组分析揭示治疗和生物学原理
尽管由于人类乳头瘤病毒(HPV)疫苗接种和筛查策略的实施,高收入国家的宫颈癌(CC)发病率有所下降,但它仍然是一个重大的公共卫生问题,对低收入国家妇女的健康构成威胁。在此,我们对139名中国女性的CC肿瘤进行了全面的蛋白质基因组分析。综合蛋白质基因组分析将基因畸变与下游发病机制相关通路联系起来,并揭示了与 HPV 相关的多组学变化。研究发现,EP300能增强FOSL2-K222的乙酰化,从而加速CC细胞的恶性增殖。蛋白质组学分层确定了在预后、基因改变、免疫浸润和翻译后修饰调节方面具有不同特征的三个患者亚群。PRKCB被进一步确定为CC患者潜在的放射反应相关生物标志物。这项研究为研究人员和临床医生提供了宝贵的公共资源,有助于他们深入研究CC的分子基础,确定潜在的治疗方法,并最终推动临床实践。
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来源期刊
Nature Communications
Nature Communications Biological Science Disciplines-
CiteScore
24.90
自引率
2.40%
发文量
6928
审稿时长
3.7 months
期刊介绍: Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.
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