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机器学习设计的免疫相关 lncRNA 特征面板预测乳腺癌的预后和免疫景观 BRCA 中的新型 IRLP 特征。

Machine Learning-Devised Immune-Related lncRNA Signature Panel Predicts the Prognosis and Immune Landscape in Breast Cancer Novel IRLP Signature in BRCA.

机构信息

Centre of Phase I Clinical Trial, Department of Medical Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510000, China.

School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China.

出版信息

J Immunol Res. 2022 Aug 18;2022:3704798. doi: 10.1155/2022/3704798. eCollection 2022.

Abstract

Long noncoding RNAs (lncRNAs) actively participate in breast cancer (BRCA) tumorigenesis via epigenetic mechanisms. Our study identified immune-related lncRNA (irlncRNA) pairs and compiled them into a set of noncoding gene signatures able to stratify subtypes of BRCA associated with variable degrees of survival and immune cell infiltration. A 40 immune-related lncRNA pair (IRLP) signature including 43 irlncRNAs was built, with high sensitivity and specificity for the prediction of survival in different molecular subtypes of BRCA. Results demonstrated that the low-risk group showed a significantly longer survival rate, and this novel IRLP signature was highly associated with survival status, T stage, metastatic disease, and overall stage in BRCA. Immune infiltrating analyses found that the low-risk group has a lower expression level of macrophage M2 and a higher expression level of immunosuppressed biomarkers than the high-risk group. DEirlncRNAs were further proven to be significantly related to the MAPK signaling, Jak-STAT signaling, and ErbB signaling pathways in BRCA. In conclusion, the 40 IRLP signature showed a promising clinical prediction value in the prognosis of different molecular subtypes and immunotherapy response in BRCA, and the underlying mechanism for these IRLPs warrants further investigations.

摘要

长非编码 RNA(lncRNA)通过表观遗传机制积极参与乳腺癌(BRCA)的肿瘤发生。我们的研究确定了免疫相关的 lncRNA(irlncRNA)对,并将其编纂成一套能够对与不同生存和免疫细胞浸润程度相关的 BRCA 亚型进行分层的非编码基因特征。构建了一个包含 43 个 irlncRNA 的 40 个免疫相关 lncRNA 对(IRLP)特征,用于预测不同 BRCA 分子亚型的生存具有较高的灵敏度和特异性。结果表明,低危组的生存率显著延长,该新型 IRLP 特征与 BRCA 中的生存状况、T 分期、转移性疾病和总分期高度相关。免疫浸润分析发现,低危组的巨噬细胞 M2 表达水平较低,免疫抑制生物标志物的表达水平较高。差异表达的 lncRNA 进一步证明与 BRCA 中的 MAPK 信号、Jak-STAT 信号和 ErbB 信号通路显著相关。总之,40 个 IRLP 特征在不同分子亚型的预后和 BRCA 免疫治疗反应中表现出有前途的临床预测价值,这些 IRLP 的潜在机制值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c80/9410861/0c340adf33ba/JIR2022-3704798.001.jpg

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