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肿瘤相关中性粒细胞中长链非编码RNA特征的计算识别可能对非小细胞肺癌的免疫治疗和预后结果产生影响。

Computational recognition of LncRNA signatures in tumor-associated neutrophils could have implications for immunotherapy and prognostic outcome of non-small cell lung cancer.

作者信息

Tang Zhuoran, Wang Qi, Chen Peixin, Guo Haoyue, Shi Jinpeng, Pan Yingying, Li Chunyu, Zhou Caicun

机构信息

Tongji University Medical School Cancer Institute, Tongji University, Shanghai, China.

Department of Medical Oncology, Tongji University Affiliated Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University, Shanghai, China.

出版信息

Front Genet. 2022 Oct 28;13:1002699. doi: 10.3389/fgene.2022.1002699. eCollection 2022.

Abstract

Cancer immune function and tumor microenvironment are governed by long noncoding RNAs (lncRNAs). Nevertheless, it has yet to be established whether lncRNAs play a role in tumor-associated neutrophils (TANs). Here, a computing framework based on machine learning was used to identify neutrophil-specific lncRNA with prognostic significance in squamous cell carcinoma and lung adenocarcinoma using univariate Cox regression to comprehensively analyze immune, lncRNA, and clinical characteristics. The risk score was determined using LASSO Cox regression analysis. Meanwhile, we named this risk score as "TANlncSig." TANlncSig was able to distinguish between better and worse survival outcomes in various patient datasets independently of other clinical variables. Functional assessment of TANlncSig showed it is a marker of myeloid cell infiltration into tumor infiltration and myeloid cells directly or indirectly inhibit the anti-tumor immune response by secreting cytokines, expressing immunosuppressive receptors, and altering metabolic processes. Our findings highlighted the value of TANlncSig in TME as a marker of immune cell infiltration and showed the values of lncRNAs as indicators of immunotherapy.

摘要

癌症免疫功能和肿瘤微环境受长链非编码RNA(lncRNAs)调控。然而,lncRNAs是否在肿瘤相关中性粒细胞(TANs)中发挥作用尚未明确。在此,基于机器学习的计算框架被用于识别在鳞状细胞癌和肺腺癌中具有预后意义的中性粒细胞特异性lncRNA,使用单变量Cox回归全面分析免疫、lncRNA和临床特征。风险评分通过LASSO Cox回归分析确定。同时,我们将此风险评分命名为“TANlncSig”。TANlncSig能够在各种患者数据集中独立于其他临床变量区分生存结局的优劣。对TANlncSig的功能评估表明,它是髓样细胞浸润到肿瘤中的标志物,髓样细胞通过分泌细胞因子、表达免疫抑制受体和改变代谢过程直接或间接抑制抗肿瘤免疫反应。我们的研究结果突出了TANlncSig在肿瘤微环境中作为免疫细胞浸润标志物的价值,并显示了lncRNAs作为免疫治疗指标的价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3259/9649922/3b0cb7cdbcf8/fgene-13-1002699-g001.jpg

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