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基于四个免疫相关长非编码 RNA 的生物信息学特征分析构建预测肾透明细胞癌预后的模型。

Bioinformatics profiling integrating a four immune-related long non-coding RNAs signature as a prognostic model for papillary renal cell carcinoma.

机构信息

Department of Urology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China.

Chongqing Key Laboratory of Molecular Oncology and Epigenetics, Chongqing, China.

出版信息

Aging (Albany NY). 2020 Jul 27;12(15):15359-15373. doi: 10.18632/aging.103580.

Abstract

BACKGROUND

Papillary renal cell carcinoma (pRCC) was the 2 most common subtype, accounting for approximately 15% incidence of renal cell carcinoma (RCC). Immune related long non-coding RNAs (IR-lncRs) plentiful in immune cells and immune microenvironment (IME) are potential in evaluating prognosis and assessing the effects of immunotherapy. A completed and meaningful IR-lncRs analysis based on abundant pRCC gene samples from The Cancer Genome Atlas (TCGA) will provide insight in this field.

RESULTS

17 IR-lncRs were selected by Pearson correlation analysis of immune score and the lncRNA expression level, and 5 sIRlncRs were significantly correlated with the OS of pRCC patients. 4 sIRlncRs (AP001267.3, AC026471.3, SNHG16 and ADAMTS9-AS1) with the most remarkable prognostic values were identified to establish the IRRS model and the OS of the low-risk group was longer than that in the high-risk group. The IRRS was certified as an independent prognosis factor and correlated with the OS. The high-risk group and low-risk group showed significantly different distributions and immune status through PCA and GSEA. In addition, we further found the expression levels of SNHG16 was remarkably enhanced in female patients with more advanced T-stages, but ADAMTS9-AS1 showed the opposite results.

CONCLUSION

The IRRS model based on the identified 4 sIRlncRs showed the significant values on forecasting prognoses of pRCC patients, with the longer OS in the low-risk group.

METHODS

We integrated the expression profiles of LncRNA and overall survival (OS) in the 322 pRCC patients based on the TCGA dataset. The immune scores calculated on account of the expression level of immune-related genes were used to verify the most relevant IR-lncRs. Survival-related IR-lncRs (sIRlncRs) were estimated by COX regression analysis in pRCC patients. The high-risk group and low-risk group were identified by the median immune-related risk score (IRRS) model established by the screened sIRlncRs. Functional annotation was displayed by gene set enrichment analysis (GSEA) and principal component analysis (PCA), and the immune composition and purity of the tumor were evaluated through microenvironment cell count records. The expression levels of sIRlncRs of pRCC samples were verified by real-time quantitative PCR.

摘要

背景

乳头状肾细胞癌(pRCC)是最常见的亚型 2,约占肾细胞癌(RCC)发病率的 15%。免疫相关的长非编码 RNA(IR-lncRs)在免疫细胞和免疫微环境(IME)中丰富,是评估预后和评估免疫治疗效果的潜在因素。基于癌症基因组图谱(TCGA)中丰富的 pRCC 基因样本进行的完整且有意义的 IR-lncRs 分析将为该领域提供深入了解。

结果

通过免疫评分与 lncRNA 表达水平的 Pearson 相关分析,选择了 17 个 IR-lncRs,其中 5 个 sIRlncRs 与 pRCC 患者的 OS 显著相关。确定了 4 个具有最显著预后价值的 sIRlncRs(AP001267.3、AC026471.3、SNHG16 和 ADAMTS9-AS1)来建立 IRRS 模型,低危组的 OS 长于高危组。IRRS 被证明是一个独立的预后因素,并与 OS 相关。通过 PCA 和 GSEA,我们发现高危组和低危组的分布和免疫状态有显著差异。此外,我们还发现,在女性患者中,SNHG16 的表达水平明显升高,T 期较晚,但 ADAMTS9-AS1 则相反。

结论

基于所鉴定的 4 个 sIRlncRs 的 IRRS 模型在预测 pRCC 患者预后方面具有显著价值,低危组的 OS 更长。

方法

我们整合了 322 例 pRCC 患者基于 TCGA 数据集的 LncRNA 和总生存期(OS)表达谱。根据免疫相关基因的表达水平计算免疫评分,以验证最相关的 IR-lncRs。通过 COX 回归分析在 pRCC 患者中评估与生存相关的 IR-lncRs(sIRlncRs)。通过筛选的 sIRlncRs 建立的高风险组和低风险组通过中位免疫相关风险评分(IRRS)模型确定。通过基因集富集分析(GSEA)和主成分分析(PCA)进行功能注释,并通过微环境细胞计数记录评估肿瘤的免疫组成和纯度。通过实时定量 PCR 验证 pRCC 样本中 sIRlncRs 的表达水平。

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