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泛素相关基因标志物可预测上皮性卵巢癌患者的免疫治疗反应和预后。

Ubiquitin-related gene markers predict immunotherapy response and prognosis in patients with epithelial ovarian carcinoma.

机构信息

First Affiliated Hospital, Department of Pathology, Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University, Shihezi University School of Medicine, Shihezi, China.

出版信息

Sci Rep. 2024 Oct 24;14(1):25239. doi: 10.1038/s41598-024-76945-2.

Abstract

Epithelial ovarian carcinoma (EOC) is the most fatal among female reproductive system tumors. The immune tumor microenvironment and ubiquitin-proteasome pathway are closely related to the proliferation, invasion, and response to chemotherapy in EOC. However, their specific roles in EOC have not been fully elucidated. Therefore, we aimed to recognize potential prognostic markers and novel therapeutic targets for EOC. We constructed the ubiquitin-related signature risk model comprising HSP90AB1, FBXO9, SIGMAR1, STAT1, SH3KBP1, EPB41L2, DNAJB6, VPS18, PPM1G, AKAP12, FRK, and PYGB, specifically for patients with EOC. The high-risk model presented a worse prognosis, primarily associated with the B-cell receptor signaling pathway, ECM receptor interaction, focal adhesion, and actin cytoskeleton regulations. Analysis of the immune landscape revealed a higher abundance of B cells, M2 macrophages, neutrophil CD4 T cells, cancer-associated fibroblasts, macrophage neutrophils, and fibroblasts in the high-risk group. It also exhibited lower tumor mutation burden, mRNAsi, and EREG-mRNAsi and reduced sensitivity to other chemotherapy drugs, except dasatinib. These findings serve as a valuable indicator for personalized treatment strategies and clinical stratification in managing patients with EOC. Additionally, our study will serve as a foundation for future mechanistic research to explore the association between the ubiquitin-proteasome pathway and EOC.

摘要

上皮性卵巢癌(EOC)是女性生殖系统肿瘤中最致命的一种。免疫肿瘤微环境和泛素-蛋白酶体通路与 EOC 的增殖、侵袭和对化疗的反应密切相关。然而,它们在 EOC 中的具体作用尚未完全阐明。因此,我们旨在确定 EOC 的潜在预后标志物和新的治疗靶点。我们构建了包含 HSP90AB1、FBXO9、SIGMAR1、STAT1、SH3KBP1、EPB41L2、DNAJB6、VPS18、PPM1G、AKAP12、FRK 和 PYGB 的泛素相关特征风险模型,专门用于 EOC 患者。高风险模型呈现出更差的预后,主要与 B 细胞受体信号通路、ECM 受体相互作用、焦点黏附以及肌动蛋白细胞骨架调节有关。免疫景观分析显示,高风险组中 B 细胞、M2 巨噬细胞、中性粒细胞 CD4 T 细胞、癌症相关成纤维细胞、巨噬细胞中性粒细胞和成纤维细胞的丰度更高。它还表现出更低的肿瘤突变负担、mRNAsi 和 EREG-mRNAsi,并降低了对其他化疗药物(除达沙替尼外)的敏感性。这些发现为管理 EOC 患者的个性化治疗策略和临床分层提供了有价值的指标。此外,我们的研究将为探索泛素-蛋白酶体通路与 EOC 之间的关联的未来机制研究奠定基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf08/11502900/a68058a7e61a/41598_2024_76945_Fig1_HTML.jpg

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