Rab11A在泛癌症中的预后和免疫意义及其在乳腺癌雌激素受体靶向中的功能和机制。

IF 1.4 4区 医学 Q4 ONCOLOGY Asia-Pacific journal of clinical oncology Pub Date : 2024-10-12 DOI:10.1111/ajco.14130
Yilun Li, Baifang Ding, Mengyu Wei, Xiaolu Yang, Ruihuan Fu, Yinfeng Liu, Lin Zhu, Yan Ding, Wenjin Zhang, Geng Zhang, Shuo Zhang, Yuhui Bu, Jianchao He, Jianye Deng, Xiaohuan Bao, Jun Hao, Li Ma
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引用次数: 0

摘要

目的Rab11A是循环内体的重要分子,与肿瘤的增殖、侵袭和转移密切相关。本研究探讨了 Rab11A 的预后和免疫意义,并验证了其在乳腺癌(BRCA)中的潜在功能和机制:方法:从癌症基因组图谱(TCGA)和基因型-组织表达数据库中下载了33个肿瘤的RNA测序数据。采用相关性分析评估 Rab11A 表达与免疫特征之间的关系。利用京都基因百科全书和基因本体分析确定了潜在的通路。免疫组化分析、菌落形成试验、溴脱氧尿苷掺入试验、免疫荧光和 Western 印迹被用来探索潜在的功能和机制:结果:对TCGA数据库的分析表明,Rab11A在多种癌症中表达显著上调。82.4%的 BRCA 中 Rab11A 表达上调。Rab11A 高表达与癌症患者生存率低有关,是预后不良的预测因子。CIBERSORT 分析显示,Rab11A 与几乎所有泛癌症免疫周期活性评分呈负相关。通过使用临床 BRCA 患者的病理样本,进一步证实了 TCGA-BRCA 队列的结果。结果显示,Rab11A 的表达与 BRCA 中雌激素受体(ER)和孕酮受体的表达相关(p 结论):泛癌症中 Rab11A 的表达与不良预后和免疫状况有关。特别是在 BRCA 中,Rab11A 的表达通过靶向 ERα 和 ERβ 来调节细胞增殖。Rab11A 的高表达与免疫特征、肿瘤微环境和基因突变密切相关。这些结果为探索 Rab11A 在泛癌症中的作用提供了参考,并为揭示 BRCA 的潜在治疗靶点提供了新的视角。
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The prognostic and immune significance of Rab11A in pan-cancer and its function and mechanism underlying estrogen receptor targeting in breast cancer.

Objective: Rab11A is an important molecule for recycling endosomes and is closely related to the proliferation, invasion, and metastasis of tumors. This study investigated the prognostic and immune significance of Rab11A and validated its potential function and mechanism in breast cancer (BRCA).

Methods: RNA sequencing data for 33 tumors were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression databases. Correlation analysis was used to evaluate the relationship between Rab11A expression and immune characteristics. Potential pathways were identified using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis. Immunohistochemical analysis, colony formation assay, bromodeoxyuridine incorporation assay, immunofluorescence, and Western blot were used to explore potential function and mechanism.

Results: Analysis of the TCGA database showed significant upregulation of Rab11A expression in a variety of cancers. Rab11A was up-regulated in 82.4% of BRCA. High Rab11A expression is associated with poor survival in cancer patients and is a predictor of poor prognosis. CIBERSORT analysis showed that Rab11A was negatively associated with almost all immune cycle activity scores pan-cancer. The results of the TCGA-BRCA cohort were further confirmed by using pathological samples from clinical BRCA patients. The results showed that Rab11A expression was correlated with estrogen receptor (ER) and progesterone receptor expression in BRCA (p < 0.05). Knockdown and overexpression of Rab11A affected the proliferation of BRCA cells. Further mechanistic studies revealed that down-regulation of ER alpha (ERα) and up-regulation of ER beta (ERβ) mediated Rab11A-induced inhibition of BRCA cell proliferation.

Conclusion: Rab11A expression in pan-cancer is associated with poor prognosis and immune profile. In particular, in BRCA, Rab11A expression regulates cell proliferation by targeting ERα and ERβ. High Rab11A expression is tightly associated with immune characteristics, tumor microenvironment, and genetic mutations. These results provide a reference for exploring the role of Rab11A in pan-cancer and provide a new perspective for revealing potential therapeutic targets in BRCA.

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来源期刊
CiteScore
3.40
自引率
0.00%
发文量
175
审稿时长
6-12 weeks
期刊介绍: Asia–Pacific Journal of Clinical Oncology is a multidisciplinary journal of oncology that aims to be a forum for facilitating collaboration and exchanging information on what is happening in different countries of the Asia–Pacific region in relation to cancer treatment and care. The Journal is ideally positioned to receive publications that deal with diversity in cancer behavior, management and outcome related to ethnic, cultural, economic and other differences between populations. In addition to original articles, the Journal publishes reviews, editorials, letters to the Editor and short communications. Case reports are generally not considered for publication, only exceptional papers in which Editors find extraordinary oncological value may be considered for review. The Journal encourages clinical studies, particularly prospectively designed clinical trials.
期刊最新文献
Issue Information COSA's 51st Annual Scientific Meeting Bridging gaps, building progress, breaking down disparities 13-15 November 2024. COSA's 51st Annual Scientific Meeting Bridging gaps, building progress, breaking down disparities 13-15 November 2024. COSA's 51st Annual Scientific Meeting Bridging gaps, building progress, breaking down disparities 13-15 November 2024. COSA's 51st Annual Scientific Meeting Bridging gaps, building progress, breaking down disparities 13-15 November 2024.
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