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构建具有膀胱癌预后意义的免疫相关 LncRNA 特征。

Construction of an immune-related LncRNA signature with prognostic significance for bladder cancer.

机构信息

Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

出版信息

J Cell Mol Med. 2021 May;25(9):4326-4339. doi: 10.1111/jcmm.16494. Epub 2021 Apr 1.

Abstract

Bladder cancer (BLCA) is one of the most common urological cancer with increasing cases and deaths every year. In the present study, we aim to construct an immune-related prognostic lncRNA signature (IRPLS) in bladder cancer (BLCA) patients and explore its immunogenomic implications in pan-cancers. First, the immune-related differentially expressed lncRNAs (IRDELs) were identified by 'limma' R package and the score of IRPLS in every patient were evaluated by Cox regression. The dysregulation of IRDELs expression between cancer and para-cancer normal tissues was validated through RT-qPCR. Then, we further explore the biological functions of a novel lncRNA from IRPLS, RP11-89 in BLCA using CCK8 assay, Transwell assay and Apoptosis analysis, which indicated that RP11-89 was able to promote cell proliferation and invasive capacity while inhibits cell apoptosis in BLCA. In addition, we performed bioinformatic methods and RIP to investigate and validate the RP11-89/miR-27a-3p/PPARγ pathway in order to explore the mechanism. Next, CIBERSORT and ESTIMATE algorithm were used to evaluate abundance of tumour-infiltrating immune cells and scores of tumour environment elements in BLCA with different level of IRPLS risk scores. Finally, multiple bioinformatic methods were performed to show us the immune landscape of these four lncRNAs for pan-cancers. In conclusion, this study first constructed an immune-related prognostic lncRNA signature, which consists of RP11-89, PSORS1C3, LINC02672 and MIR100HG and might shed lights on novel targets for individualized immunotherapy for BLCA patients.

摘要

膀胱癌(BLCA)是最常见的泌尿系统癌症之一,每年的病例和死亡人数都在不断增加。在本研究中,我们旨在构建膀胱癌(BLCA)患者的免疫相关预后长链非编码 RNA 特征(IRPLS),并探讨其在泛癌中的免疫基因组学意义。首先,通过 'limma' R 包识别免疫相关差异表达的长链非编码 RNA(IRDELs),并通过 Cox 回归评估每个患者的 IRPLS 评分。通过 RT-qPCR 验证癌症和癌旁正常组织中 IRDELs 表达的失调。然后,我们使用 CCK8 测定、Transwell 测定和细胞凋亡分析进一步探讨来自 IRPLS 的新型长链非编码 RNA RP11-89 在 BLCA 中的生物学功能,结果表明 RP11-89 能够促进 BLCA 中的细胞增殖和侵袭能力,同时抑制细胞凋亡。此外,我们进行了生物信息学方法和 RIP 以研究和验证 RP11-89/miR-27a-3p/PPARγ通路,以探索其机制。接下来,使用 CIBERSORT 和 ESTIMATE 算法评估不同 IRPLS 风险评分的 BLCA 中肿瘤浸润免疫细胞的丰度和肿瘤环境元素的评分。最后,通过多种生物信息学方法展示了这四个长链非编码 RNA 在泛癌中的免疫景观。总之,本研究首次构建了一个免疫相关的预后长链非编码 RNA 特征,由 RP11-89、PSORS1C3、LINC02672 和 MIR100HG 组成,可能为 BLCA 患者的个体化免疫治疗提供新的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f887/8093983/2f50cd28c203/JCMM-25-4326-g004.jpg

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