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ACTR3 在宫颈癌中的表达及其对免疫细胞浸润和预后的影响:基于 bulk RNA-Seq 和单细胞 RNA-Seq 的综合分析

英文原题:Expression of ACTR3 in cervical cancer and impact on immune cell infiltration and prognosis: A comprehensive analysis based on bulk RNA-Seq and single-cell RNA-Seq.

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Expression of ACTR3 in cervical cancer and impact on immune cell infiltration and prognosis: A comprehensive analysis based on bulk RNA-Seq and single-cell RNA-Seq.

PubMed 2025/12/05(内容时间) Medicine (Baltimore) Q2 · IF 2(JCR 2025)

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研究概要

本研究阐明了一种与 PI3K/Akt/mTOR 信号通路相关的独特特征,特别关注 ACTR3,其在 CESC 的发生和进展中均发挥作用。此外,ACTR3 有潜力作为诊断为 CESC 患者的预后生物标志物,从而为临床治疗方法的开发提供了新的视角。

研究思路结论见上方概要

PI3K/Akt/mTOR通路在某些癌症中至关重要,但其与宫颈鳞状细胞癌和宫颈腺癌(CESC)中肿瘤浸润免疫细胞的关系尚未被分析。本研究旨在确定ACTR3过表达是否影响CC生存,并探讨其对肿瘤免疫微环境的影响。

研究探讨了ACTR3表达水平与PI3K/Akt/mTOR通路的关系及其对肿瘤免疫学和临床结局的影响。方法包括RNA-seq数据分析、免疫细胞浸润评估、生存分析、基因富集分析和单细胞RNA-seq数据整合。通过免疫组织化学评估宫颈癌标本中ACTR3的表达。

最小绝对收缩和选择算子(LASSO)Cox回归识别出包括ACTR3在内的十个具有预后价值的关键基因。ACTR3高表达与不良结局相关,提示其可作为预后生物标志物。该预后模型通过1年、3年和5年生存的时间依赖性受试者工作特征(ROC)曲线进行了验证。结合ACTR3表达和临床参数的列线图可估计患者生存。单细胞RNA测序显示,CESC中表达ACTR3的免疫细胞包括树突状细胞(DCs)、T细胞和组织干细胞。

展开英文摘要原文

PI3K/Akt/mTOR pathway is crucial in some cancers, but its relation with tumor-infiltrating immune cells in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is unanalyzed. This study aimed to determine if ACTR3 overexpression affects CC survival and explore its impact on the tumor immune microenvironment.

Research investigated ACTR3 expression levels related to PI3K/Akt/mTOR pathway and its influence on tumor immunology and clinical outcomes. Methods included RNA-seq data analysis, immune cell infiltration evaluation, survival analysis, gene enrichment analysis, and single-cell RNA-seq data integration. ACTR3 expression in cervical cancer specimens was evaluated by immunohistochemistry.

Least absolute shrinkage and selection operator (LASSO) Cox regression identified ten key genes including ACTR3 with prognostic value. High ACTR3 expression correlated with poor outcomes, suggesting it as a prognostic biomarker. The prognostic model was validated by time-dependent receiver operating characteristic (ROC) curves for 1-, 3-, and 5-year survival. A nomogram combining ACTR3 expression and clinical parameters estimated patient survival. Single-cell RNA sequencing showed ACTR3-expressing immune cells in CESC include dendritic cells (DCs), T cells, and tissue stem cells.

This research elucidated a distinct signature linked to the PI3K/Akt/mTOR signaling pathway, particularly focusing on ACTR3, which plays a role in both the onset and advancement of CESC. Moreover, ACTR3 has the potential to act as a prognostic biomarker for patients diagnosed with CESC, thereby offering novel perspectives for the development of clinical therapeutic approaches.

论文信息

作者
Wang H、Zhang J、Li J、Sun B、Wu Y、Wang H、Chen X、Shang X
第一作者单位
Lianyungang Maternal and Child Health Hospital, Lianyungang, Jiangsu, China.China
通讯作者单位
Department of Laboratory Medicine, Lianyungang Affiliated Hospital of Nanjing University of Chinese Medicine, Lianyungang, Jiangsu, China.China
期刊
Medicine2025 Dec 5
原文标识
PubMed 41366959 · DOI 10.1097/MD.0000000000046316