Immune associated LncRNAs identify novel prognostic subtypes of renal clear cell carcinoma
Immune associated LncRNAs identify novel prognostic subtypes of renal clear cell carcinoma
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DOI：
10.1002/mc.22949
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发表时间：
2019-04-01
影响因子：
4.6
通讯作者：
Shukla, Sudhanshu Kumar
中科院分区：
文献类型：
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作者：
Khadirnaikar, Seema;Kumar, Pranjal;Shukla, Sudhanshu Kumar
肾透明细胞癌(KIRC)是癌症相关死亡的重要原因。在这里，我们的目标是识别与免疫系统相关的lncRNAs，并表征它们在KIRC中的临床应用。共504例患者的数据来自TCGA-GDC。电子相关分析发现143个LncRNA与免疫相关基因相关(r>；0.7，P<；0.05)。K-Means Consensus方法基于143个免疫相关lncRNAs的表达，将KIRC样本聚类到三个免疫簇，即簇C1、C2和C3。卡普兰-迈耶分析显示，C3组患者的存活率明显低于其他两组(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(-8))。GSEA和CiberSort分析显示，C3患者中活性较差的T细胞高度浓缩。为了定义lncRNA免疫预后特征，我们将TCGA样本随机分为发现集和验证集。通过多因素COX回归分析，我们确定并验证了KIRC的7个lncRNA免疫预后标志性评分(LIPS评分)(HR=1.43，P=2.73×10(-6))。将LIPS评分与所有临床因素进行比较，验证了其在判断KIRC预后中的独立性和优越性。综上所述，我们确定了与免疫系统相关的lncRNA，并根据免疫相关的lncRNA表达显示了KIRC患者预后亚型的存在。我们还发现了一种新的基于免疫LncRNA的基因标记用于KIRC患者的预测。
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 x 10(-8)). 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 x 10(-6)) 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.