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, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Nat Commun. 2024 Nov 22;15(1):10114. doi: 10.1038/s41467-024-53830-0.
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.
尽管由于人乳头瘤病毒 (HPV) 疫苗接种和筛查策略，高收入国家的宫颈癌 (CC) 发病率已经降低，但它仍然是一个重大的公共卫生问题，对低收入国家的妇女健康构成威胁。在这里，我们对来自 139 名中国女性的 CC 肿瘤进行了全面的蛋白质基因组学分析。综合蛋白质基因组学分析将遗传异常与下游发病机制相关途径联系起来，并揭示了 HPV 相关多组学变化的情况。发现 EP300 增强了 FOSL2-K222 的乙酰化作用，从而加速了 CC 细胞的恶性增殖。蛋白质组学分层确定了具有不同预后、遗传改变、免疫浸润和翻译后修饰调节特征的三个患者亚组。PRKCB 进一步被鉴定为 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有价值的公共资源，以深入研究 CC 的分子基础，确定潜在的治疗方法，并最终推进临床实践。
