Table_1_Impact of Long Non-coding RNAs Associated With Microenvironment on Survival for Bladder Cancer Patients.docx

BackgroundCumulative evidence from several tumor studies, including bladder cancer, emphasizes the importance of the tumor microenvironment (TME) in tumorigenesis, development, and metastasis, which can be regulated by long non-coding RNAs (lncRNAs). This study aims to identify bladder cancer (BC) microenvironment–associated lncRNAs for their prognostic value predicting the survival of BC patients.
MethodsThe data of BC patients regarding lncRNA expression and corresponding clinical characteristics were obtained from The Cancer Genome Atlas (TCGA). The Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression analysis were performed to screen lncRNAs following the calculation of the immune score for each sample. For the screened lncRNAs, a risk score model was constructed to predict the survival, and 3- and 5-year overall survival (OS) rates were assessed using a nomogram. The calibration curve and concordance index (C-index) validated the performance of the nomogram. Finally, to explore the potential function related to the screened lncRNAs, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed.
ResultsThe multivariate Cox regression analysis screened five TME-associated lncRNAs regarded as independent factors influencing the tumor progression. The corresponding risk score model was established as follows: (−0.15816 AC064805.1) + (0.10015 AC084033.3) + (−0.17977 AC092112.1) + (−0.05673AC103691.1) + (0.17789 AL391704.1) + (−0.16258 LINC00892). The C-index for the nomogram was 0.63 (95% CI: 0.625–0.635). Also, the calibration curve verified the predictive effectiveness by showing a good concordance between the nomogram prediction and the actual observation. GO and KEGG analysis demonstrated that six TME-associated lncRNAs were most likely linked to tumor metastasis and progression.
ConclusionThe present study determined six lncRNAs as independent immuno-biomarkers in the TME, constructed a nomogram to predict their prognostic value, and investigated the potential biological processes to understand their regulatory roles in the progression of BC.

背景：多项包括膀胱癌（bladder cancer, BC）在内的肿瘤研究积累的证据表明，肿瘤微环境（tumor microenvironment, TME）在肿瘤发生、发展及转移过程中发挥关键作用，而长链非编码RNA（long non-coding RNAs, lncRNAs）可对其进行调控。本研究旨在筛选与膀胱癌微环境相关的长链非编码RNA，并探讨其在预测膀胱癌患者生存预后中的价值。
方法：本研究从癌症基因组图谱（The Cancer Genome Atlas, TCGA）数据库中获取膀胱癌患者的长链非编码RNA表达数据及对应的临床特征信息。首先计算所有样本的免疫评分，随后通过Cox回归分析与最小绝对收缩和选择算子（least absolute shrinkage and selection operator, LASSO）回归分析筛选目标长链非编码RNA。基于筛选得到的长链非编码RNA构建风险评分模型以预测患者生存情况，并利用列线图（nomogram）评估3年及5年总生存期（overall survival, OS）率。通过校准曲线与一致性指数（concordance index, C-index）验证列线图的预测性能。最后，为探究筛选得到的长链非编码RNA的潜在功能，本研究开展了基因本体论（gene ontology, GO）与京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）富集分析。
结果：多因素Cox回归分析筛选出5个与肿瘤微环境相关的长链非编码RNA，这些RNA可作为影响肿瘤进展的独立危险因素。构建的风险评分模型公式如下：(−0.15816 AC064805.1) + (0.10015 AC084033.3) + (−0.17977 AC092112.1) + (−0.05673AC103691.1) + (0.17789 AL391704.1) + (−0.16258 LINC00892)。该列线图的一致性指数为0.63（95%置信区间：0.625–0.635），校准曲线显示列线图预测结果与实际观测值具有良好的一致性，验证了其预测效能。基因本体论与京都基因与基因组百科全书富集分析结果显示，6个肿瘤微环境相关长链非编码RNA可能与肿瘤转移及进展密切相关。
结论：本研究明确了6个可作为肿瘤微环境独立免疫生物标志物的长链非编码RNA，构建了用于预测其预后价值的列线图，并通过探究潜在生物学过程以阐明其在膀胱癌进展中的调控作用。