Department of Biosciences and Bioengineering, Indian Institute of Technology Dharwad, Dharwad, Karnataka.
Michigan Center for Pathology, Department of Pathology, University of Michigan, Ann Arbor, Michigan.
Mol Carcinog. 2019 Apr;58(4):544-553. doi: 10.1002/mc.22949. Epub 2018 Dec 21.
Kidney Renal Clear Cell Carcinoma (KIRC) is a significant cause of cancer-related deaths. Here, we aim to identify the LncRNAs associated with the immune system and characterise their clinical utility in KIRC. A total of 504 patients' data was used from TCGA-GDC. In silico correlation analysis identified 143 LncRNAs associated with immune-related genes (r > 0.7, P < 0.05). K-means consensus method clustered KIRC samples in three immune clusters, namely cluster C1, C2, and C3 based on the expression of 143 immune-related LncRNAs. Kaplan-Meier analysis showed that C3 patients survived significantly worse than the other two clusters (P < 0.0001). A comparison of TCGA miRNA, mRNA cluster with immune cluster showed the independence and robustness of immune clusters (HR = 2.02 and P = 2.12 × 10 ). The GSEA and CIBERSORT analysis showed high enrichment of poorly activated T-cells in C3 patients. To define LncRNA immune prognostic signature, we randomly divided the TCGA sample into discovery and validation sets. By utilising multivariate Cox regression analysis, we identified and validated a seven LncRNA immune prognostic signature score (LIPS score) (HR = 1.43 and P = 2.73 × 10 ) in KIRC. Comparison of LIPS score with all the clinical factors validated its independence and superiority in KIRC prognosis. In summary, we identified LncRNAs associated with the immune system and showed the presence of prognostic subtypes of KIRC patients based on immune-related LncRNA expression. We also identified a novel immune LncRNA based gene-signature for KIRC patients' prognostication.
肾透明细胞癌（KIRC）是癌症相关死亡的重要原因。在这里，我们旨在鉴定与免疫系统相关的 LncRNAs，并描述它们在 KIRC 中的临床应用价值。总共使用了来自 TCGA-GDC 的 504 名患者的数据。通过计算相关分析，鉴定出 143 个与免疫相关基因相关的 LncRNA（r>0.7，P<0.05）。基于 143 个免疫相关 LncRNA 的表达，K-means 共识聚类方法将 KIRC 样本聚类为三个免疫簇，即簇 C1、C2 和 C3。Kaplan-Meier 分析表明，C3 患者的生存明显差于其他两个簇（P<0.0001）。TCGA miRNA、mRNA 簇与免疫簇的比较表明，免疫簇具有独立性和稳健性（HR=2.02，P=2.12×10）。GSEA 和 CIBERSORT 分析表明，C3 患者中活化不良的 T 细胞高度富集。为了定义 LncRNA 免疫预后标志，我们随机将 TCGA 样本分为发现和验证集。通过利用多变量 Cox 回归分析，我们鉴定并验证了一个由七个 LncRNA 免疫预后标志组成的评分（LIPS 评分）（HR=1.43，P=2.73×10）在 KIRC 中。LIPS 评分与所有临床因素的比较验证了其在 KIRC 预后中的独立性和优越性。总之，我们鉴定了与免疫系统相关的 LncRNAs，并基于免疫相关 LncRNA 的表达，显示了 KIRC 患者存在预后亚型。我们还确定了一种新的基于免疫 LncRNA 的 KIRC 患者预后基因标志。
