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Construction of a Novel Immune-Related lncRNA Pair Signature with Prognostic Significance for Kidney Clear Cell Renal Cell Carcinoma
Disease Markers Pub Date : 2021-09-02 , DOI: 10.1155/2021/8800358
Jian-Xuan Sun 1 , Qi-Dong Xia 1 , Chen-Qian Liu 1 , Jin-Zhou Xu 1 , Yang Xun 1 , Jun-Lin Lu 1 , Jia Hu 1 , Shao-Gang Wang 1
Affiliation  

Background. Renal cell carcinoma (RCC) is one of the most common aggressive malignant tumors in the urinary system, among which the clear cell renal cell carcinoma (ccRCC) is the most common subtype. The immune-related long noncoding ribonucleic acids (irlncRNAs) which are abundant in immune cells and immune microenvironment (IME) have potential significance in evaluating the prognosis and effects of immunotherapy. The signature based on irlncRNA pairs and independent of the exact expression level seems to have a latent predictive significance for the prognosis of patients with malignant tumors but has not been applied in ccRCC yet. Method. In this article, we retrieved The Cancer Genome Atlas (TCGA) database for the transcriptome profiling data of the ccRCC and performed coexpression analysis between known immune-related genes (ir-genes) and lncRNAs to find differently expressed irlncRNA (DEirlncRNA). Then, we adopted a single-factor test and a modified LASSO regression analysis to screen out ideal DEirlncRNAs and constructed a Cox proportional hazard model. We have sifted 28 DEirlncRNA pairs, 12 of which were included in this model. Next, we compared the area under the curve (AUC), found the cutoff point by using the Akaike information criterion (AIC) value, and distinguished the patients with ccRCC into a high-risk group and a low-risk group using this value. Finally, we tested this model by investigating the relationship between risk score and survival, clinical pathological characteristics, cells in tumor immune microenvironment, chemotherapy, and targeted checkpoint biomarkers. Results. A novel immune-related lncRNA pair signature consisting of 12 DEirlncRNA pairs was successfully constructed and tightly associated with overall survival, clinical pathological characteristics, cells in tumor immune microenvironment, and reactiveness to immunotherapy and chemotherapy in patients with ccRCC. Besides, the efficacy of this signature was verified in some commonly used clinicopathological subgroups and could serve as an independent prognostic factor in patients with ccRCC. Conclusions. This signature was proven to have a potential predictive significance for the prognosis of patients with ccRCC and the efficacy of immunotherapy.

中文翻译:

构建对肾透明细胞肾细胞癌具有预后意义的新型免疫相关 lncRNA 对特征

背景。肾细胞癌(RCC)是泌尿系统最常见的侵袭性恶性肿瘤之一,其中透明细胞肾细胞癌(ccRCC)是最常见的亚型。免疫细胞和免疫微环境(IME)中丰富的免疫相关长链非编码核糖核酸(irlncRNAs)对评估免疫治疗的预后和效果具有潜在意义。基于 irlncRNA 对且独立于确切表达水平的特征似乎对恶性肿瘤患者的预后具有潜在的预测意义,但尚未应用于 ccRCC。方法. 在本文中,我们检索了癌症基因组图谱 (TCGA) 数据库中的 ccRCC 转录组分析数据,并在已知免疫相关基因 (ir-genes) 和 lncRNA 之间进行了共表达分析,以找到不同表达的 irlncRNA (DEirlncRNA)。然后,我们采用单因素检验和改进的LASSO回归分析筛选出理想的DEirlncRNA,并构建了Cox比例风险模型。我们筛选了 28 个 DEirlncRNA 对,其中 12 个包含在该模型中。接下来,我们比较了曲线下面积(AUC),使用Akaike信息标准(AIC)值找到了截止点,并根据该值将ccRCC患者区分为高危组和低危组。最后,我们通过调查风险评分和生存率之间的关系来测试这个模型,结果。成功构建了由 12 个 DEirlncRNA 对组成的新型免疫相关 lncRNA 对特征,并与 ccRCC 患者的总生存期、临床病理特征、肿瘤免疫微环境中的细胞以及对免疫治疗和化疗的反应性密切相关。此外,该特征的有效性在一些常用的临床病理学亚组中得到验证,可作为 ccRCC 患者的独立预后因素。结论。该特征被证明对ccRCC患者的预后和免疫疗法的疗效具有潜在的预测意义。
更新日期:2021-09-02
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