Hu Wei, Wang Yanru, Fang Zhixiao, He Wei, Li Shengli
Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Nuclear Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, China.
Front Cell Dev Biol. 2021 Feb 16;9:641891. doi: 10.3389/fcell.2021.641891. eCollection 2021.
Prostate cancer is among the top mortality factors in male around the world. Long non-coding RNAs (lncRNAs) have been shown to play crucial roles in tumor biology and immunology. However, lncRNA-immune interactions have not yet examined in prostate cancer. Here, we performed integrated analysis to characterize lncRNA-immune interactions in prostate cancer through multidimensional aspects, including immune-related hallmarks, tumor immunogenomic signatures, immune-related biological processes, immune cells, and immune checkpoints. We dissected the dysregulation of lncRNAs and their clinical relevance in prostate cancer, such as RP11-627G23.1 and RP11-465N4.5. Immune-related hallmarks took up the major parts among top significant lncRNA-hallmark interactions. Our analysis revealed that TGF-β signaling pathway was the most frequent to associate with lncRNAs, which is a signature of immune response in cancer. In addition, immune response and its regulation were the most closely connected immunological processes with lncRNA, implying the regulatory roles of lncRNAs on immune response in prostate cancer. We found that memory resting CD4 T cells were the most lncRNA-correlated immune cell. LINC00861 was found to be potentially intervening targets of immunotherapy for prostate cancer patients, which was significantly associated with PD-1 and CTLA4. Collectively, we offered a handy resource to investigate regulatory roles of lncRNAs on tumor immunology and the development of clinical utility of lncRNAs in prostate cancer.
前列腺癌是全球男性主要的死亡因素之一。长链非编码RNA（lncRNAs）已被证明在肿瘤生物学和免疫学中发挥关键作用。然而，lncRNA与免疫的相互作用在前列腺癌中尚未得到研究。在此，我们进行了综合分析，从免疫相关特征、肿瘤免疫基因组特征、免疫相关生物学过程、免疫细胞和免疫检查点等多维度来表征前列腺癌中的lncRNA与免疫的相互作用。我们剖析了lncRNAs的失调及其在前列腺癌中的临床相关性，如RP11-627G23.1和RP11-465N4.5。在最显著的lncRNA-特征相互作用中，免疫相关特征占主要部分。我们的分析表明，转化生长因子-β（TGF-β）信号通路是与lncRNAs关联最频繁的通路，这是癌症免疫反应的一个特征。此外，免疫反应及其调节是与lncRNA联系最紧密的免疫过程，这意味着lncRNAs在前列腺癌免疫反应中具有调节作用。我们发现记忆性静息CD4 T细胞是与lncRNA相关性最高的免疫细胞。LINC00861被发现可能是前列腺癌患者免疫治疗的干预靶点，它与程序性死亡受体1（PD-1）和细胞毒性T淋巴细胞相关抗原4（CTLA4）显著相关。总的来说，我们提供了一个便捷的资源，用于研究lncRNAs在肿瘤免疫学中的调节作用以及lncRNAs在前列腺癌临床应用中的发展。
