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乳腺癌免疫治疗中迁移细胞增多症和血管生成相关长链非编码RNA特征的鉴定

Identification of a migracytosis and angiogenesis-associated lncRNAs signature in immunotherapy in breast cancer.

作者信息

Qiu Yier, Li Mengting, Qiu Qianhui, Lu Guowen

机构信息

Department of Thyroid and Breast Surgery, The Affiliated People's Hospital of Ningbo University, Ningbo, 315040, Zhejiang, China.

Department of Gastroenterology, The Affiliated People's Hospital of Ningbo University, Ningbo, 315040, Zhejiang, China.

出版信息

J Appl Genet. 2025 May 30. doi: 10.1007/s13353-025-00977-1.

Abstract

Migracytosis and angiogenesis were crucial in breast cancer (BRCA) progression. This study aimed to develop a prognostic signature based on migracytosis- and angiogenesis-related lncRNAs. All genetic and clinical data of BRCA were acquired from The Cancer Genome Atlas (TCGA) database. A prognostic signature consisting of six lncRNAs (YTHDF3-AS1, AC018445.5, AP005131.1, AC010531.3, MIR200CHG, and AC000067.1) was established through correlation and Cox regression analysis, as well as the least absolute shrinkage and selection operator (LASSO) test. The BRCA patients from TCGA were categorized into high-risk and low-risk subgroups. Nomograms, calibration plots, Kaplan-Meier survival curves, and receiver operating characteristic (ROC) curves were used to evaluate the overall survival (OS) and predictive value of the signature. To explore the biological functions of migracytosis- and angiogenesis-related lncRNAs, enrichment analysis, tumor mutation burden (TMB), and the ESTIMATE algorithm were performed. Additionally, consensus clustering was applied to categorize tumor subtypes, and the disparity among all clusters was assessed, including drug sensitivity and immunotherapeutic efficacy. The expression levels of prognostic lncRNAs were validated using RT-PCR, while their functional impact on cell proliferation was assessed via the Cell Counting Kit-8 (CCK-8) assay in vitro. The results indicated that patients in the high-risk subgroup had a worse prognosis, higher TMB, stronger immune response, and greater sensitivity to immunotherapy. In summary, the prognostic risk signature based on migracytosis- and angiogenesis-related lncRNAs was associated with the clinical prognosis of BRCA patients. The signature's risk score could potentially be used to predict clinical classification and therapeutic efficacy.

摘要

迁移细胞增多和血管生成在乳腺癌(BRCA)进展中至关重要。本研究旨在基于迁移细胞增多和血管生成相关的长链非编码RNA(lncRNA)开发一种预后特征。BRCA的所有基因和临床数据均从癌症基因组图谱(TCGA)数据库中获取。通过相关性分析、Cox回归分析以及最小绝对收缩和选择算子(LASSO)检验,建立了一个由六个lncRNA(YTHDF3-AS1、AC018445.5、AP005131.1、AC010531.3、MIR200CHG和AC000067.1)组成的预后特征。将来自TCGA的BRCA患者分为高风险和低风险亚组。使用列线图、校准图、Kaplan-Meier生存曲线和受试者工作特征(ROC)曲线来评估总生存期(OS)和该特征的预测价值。为了探究迁移细胞增多和血管生成相关lncRNA的生物学功能,进行了富集分析、肿瘤突变负荷(TMB)分析和ESTIMATE算法分析。此外,应用一致性聚类对肿瘤亚型进行分类,并评估所有聚类之间的差异,包括药物敏感性和免疫治疗疗效。使用逆转录-聚合酶链反应(RT-PCR)验证预后lncRNA的表达水平,同时通过体外细胞计数试剂盒-8(CCK-8)试验评估它们对细胞增殖的功能影响。结果表明,高风险亚组的患者预后较差、TMB较高、免疫反应较强且对免疫治疗更敏感。总之,基于迁移细胞增多和血管生成相关lncRNA的预后风险特征与BRCA患者的临床预后相关。该特征的风险评分可能可用于预测临床分类和治疗疗效。

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