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溶酶体相关分子亚型揭示卵巢癌的预后特征及免疫治疗意义。

Lysosome-related molecular subtypes reveal prognostic signatures and immunotherapeutic implications in ovarian cancer.

作者信息

Fang Zhou, Liu Yunqing, Cui Yujie, Cao Ke, Han Yiling, Gao Zhijie

机构信息

Department of Oncology, Third Xiangya Hospital, Central South University, Changsha, China.

Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.

出版信息

Sci Rep. 2025 Sep 25;15(1):32898. doi: 10.1038/s41598-025-18271-9.

Abstract

Lysosomes are critical organelles that act as degradation centers and signaling hubs within cells, playing a significant role in various cellular processes and human diseases, including cancer. However, the extent to which they influence the heterogeneity and clinical outcomes of ovarian cancer (OC) remains inadequately understood. In this study, we used consensus clustering to identify two distinct lysosome-related clusters (LCs) in OC by analyzing the expression profiles of OC patients from The Cancer Genome Atlas (TCGA) database. Further analyses revealed the functional characteristics and immune landscapes of these subgroups, providing valuable insights into the tumor immune microenvironment (TIME) and tumor responses to immunotherapy. Additionally, we developed and validated a prognostic model based on differentially expressed genes (DEGs) between the two LCs, demonstrating its effectiveness in predicting patient prognosis, TIME characteristics, and immunotherapy potential in OC. A further investigation explored the relationship between lysosome-associated risk scores, IC50 values of standard antitumor agents, and the expression levels of prognostic genes. Finally, in vitro experiments showed that inhibiting CRHR1, a lysosome-associated prognostic gene, significantly reduced OC cell proliferation, invasion, and migration. In conclusion, our study establishes a novel lysosome-based classification and prognostic framework for OC, offering a practical tool to predict clinical outcomes and guide personalized immunotherapy strategies.

摘要

溶酶体是重要的细胞器,在细胞内充当降解中心和信号枢纽,在包括癌症在内的各种细胞过程和人类疾病中发挥着重要作用。然而,它们对卵巢癌(OC)异质性和临床结果的影响程度仍未得到充分了解。在本研究中,我们通过分析来自癌症基因组图谱(TCGA)数据库的OC患者的表达谱,使用共识聚类法在OC中识别出两个不同的溶酶体相关簇(LCs)。进一步的分析揭示了这些亚组的功能特征和免疫格局,为肿瘤免疫微环境(TIME)和肿瘤对免疫治疗的反应提供了有价值的见解。此外,我们基于两个LC之间的差异表达基因(DEGs)开发并验证了一个预后模型,证明了其在预测OC患者预后、TIME特征和免疫治疗潜力方面的有效性。进一步的研究探讨了溶酶体相关风险评分、标准抗肿瘤药物的IC50值与预后基因表达水平之间的关系。最后,体外实验表明,抑制溶酶体相关预后基因CRHR1可显著降低OC细胞的增殖、侵袭和迁移。总之,我们的研究为OC建立了一个基于溶酶体的新型分类和预后框架,提供了一个预测临床结果和指导个性化免疫治疗策略的实用工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9126/12464291/8e3ba7e9e3a5/41598_2025_18271_Fig1_HTML.jpg

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