免疫相关lncRNA对的鉴定及结肠癌新预后标记的构建与验证

IF 2.7 4区 医学 Q2 Medicine Canadian Journal of Gastroenterology and Hepatology Pub Date : 2022-03-30 DOI:10.1155/2022/5827544
Mi-duo Xu, Qing Li, Jianfang Zhang, Hui Xie
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Univariate Cox regression analysis, LASSO penalized regression analysis, and multivariate Cox regression analysis were performed to determine the final variables to construct the prognostic risk score model (a new signature). We draw the receiver operating characteristic (ROC) curves of the signature and clinical characteristics and determine the optimal cutoff value by the optimal Akaike Information Criterion (AIC) value. Based on the optimal cutoff value of the ROC curve of the signature, colon cancer patients were divided into the high- and low-risk groups. Then, the signature was evaluated by clinicopathological features, tumor-infiltrating immune cells, checkpoint-related biomarkers, targeted therapy, and chemotherapy. Results We identified 8 lncRNA pairs including AC103740.1|LEF1-AS1, LINC02391|AC053503.5, WWC2-AS2|AL355916.2, AC104090.1|NEURL1-AS1, AC099524.1|AL161908.1, AC074011.1|AL078601.2, AL355916.2|LINC01723, and AP003392.4|LINC00598 from 71 differently expressed irlncRNAs. We constructed a prognostic risk score model (a new signature) using these optimal eight irlncRNA pairs. ROC curve analysis revealed that the highest AUC value of the signature was 0.776 at 1 year, with the optimal cutoff value of 1.283. Our present study also showed that the constructed signature could accurately identify adverse survival outcomes, prognostic clinicopathological features, and specify tumor invasion status. The expression of immune checkpoint-related genes and chemical drug sensitivity were related to different risk groups. Conclusion In our present study, we constructed a new irlncRNA signature of colon cancer based on the irlncRNA pairs instead of the special expression level of lncRNA. 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引用次数: 3

摘要

越来越多的证据表明,免疫相关的长链非编码核糖核酸(irlncRNAs)是结肠癌的潜在预后因素。相关基因对模式可提高预后模型的敏感性。因此,我们目前的研究旨在鉴定irlncRNA对,构建并验证结肠癌预后的新特征。方法从TCGA公共数据库下载结肠癌患者mRNA和lncRNA的表达矩阵及其临床资料。我们从进口数据库中获得了免疫基因。进行共表达分析以鉴定irlncRNAs。通过比较每个lncRNA对在一个周期中的表达水平,我们构建了irlncRNA对矩阵。采用单因素Cox回归分析、LASSO惩罚回归分析和多因素Cox回归分析确定最终变量,构建预后风险评分模型(新签名)。绘制特征与临床特征的受试者工作特征(ROC)曲线,通过最佳赤池信息准则(AIC)值确定最佳截断值。根据特征ROC曲线的最佳截断值,将结肠癌患者分为高危组和低危组。然后,通过临床病理特征、肿瘤浸润免疫细胞、检查点相关生物标志物、靶向治疗和化疗来评估该特征。结果从71个不同表达的irlncrna中鉴定出8对lncRNA,包括AC103740.1|LEF1-AS1、LINC02391|AC053503.5、WWC2-AS2|AL355916.2、AC104090.1|NEURL1-AS1、AC099524.1|AL161908.1、AC074011.1|AL078601.2、AL355916.2|LINC01723和AP003392.4|LINC00598。我们利用这8对最优irlncRNA构建了预后风险评分模型(一种新的特征)。ROC曲线分析显示,1年时该特征的最高AUC值为0.776,最佳截断值为1.283。我们目前的研究还表明,构建的特征可以准确识别不良生存结局、预后临床病理特征,并明确肿瘤侵袭状态。免疫检查点相关基因表达及化学药物敏感性与不同危险人群相关。结论在我们的研究中,我们基于irlncRNA对而不是lncRNA的特殊表达水平构建了结肠癌新的irlncRNA特征。我们发现该特征不仅具有良好的预后价值,而且具有一定的临床价值,可能为结肠癌的治疗和预后提供新的认识。
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Identification of Immune-Related lncRNA Pairs and Construction and Validation of a New Prognostic Signature of Colon Cancer
Background More and more evidence has shown that immune-related long noncoding ribonucleic acid (irlncRNAs) is a potential prognostic factor for colon cancer. The relevant gene pair pattern can improve the sensitivity of the prognostic model. Therefore, our present study aimed to identify irlncRNA Pairs and construct and validate a new prognostic signature in colon cancer. Methods We downloaded the expression matrix of mRNA and lncRNA of patients with colon cancer and their clinical information from the public TCGA database. We obtained immune genes from the ImmPort database. Coexpression analysis was performed to identify irlncRNAs. We built an irlncRNA pair matrix by comparing the expression levels of each lncRNA pair in a cycle. Univariate Cox regression analysis, LASSO penalized regression analysis, and multivariate Cox regression analysis were performed to determine the final variables to construct the prognostic risk score model (a new signature). We draw the receiver operating characteristic (ROC) curves of the signature and clinical characteristics and determine the optimal cutoff value by the optimal Akaike Information Criterion (AIC) value. Based on the optimal cutoff value of the ROC curve of the signature, colon cancer patients were divided into the high- and low-risk groups. Then, the signature was evaluated by clinicopathological features, tumor-infiltrating immune cells, checkpoint-related biomarkers, targeted therapy, and chemotherapy. Results We identified 8 lncRNA pairs including AC103740.1|LEF1-AS1, LINC02391|AC053503.5, WWC2-AS2|AL355916.2, AC104090.1|NEURL1-AS1, AC099524.1|AL161908.1, AC074011.1|AL078601.2, AL355916.2|LINC01723, and AP003392.4|LINC00598 from 71 differently expressed irlncRNAs. We constructed a prognostic risk score model (a new signature) using these optimal eight irlncRNA pairs. ROC curve analysis revealed that the highest AUC value of the signature was 0.776 at 1 year, with the optimal cutoff value of 1.283. Our present study also showed that the constructed signature could accurately identify adverse survival outcomes, prognostic clinicopathological features, and specify tumor invasion status. The expression of immune checkpoint-related genes and chemical drug sensitivity were related to different risk groups. Conclusion In our present study, we constructed a new irlncRNA signature of colon cancer based on the irlncRNA pairs instead of the special expression level of lncRNA. We found this signature had not only good prognostic value but also certain clinical value, which might provide a new insight into the treatment and prognosis of colon cancer.
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CiteScore
4.80
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审稿时长
37 weeks
期刊介绍: Canadian Journal of Gastroenterology and Hepatology is a peer-reviewed, open access journal that publishes original research articles, review articles, and clinical studies in all areas of gastroenterology and liver disease - medicine and surgery. The Canadian Journal of Gastroenterology and Hepatology is sponsored by the Canadian Association of Gastroenterology and the Canadian Association for the Study of the Liver.
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