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免疫相关长链非编码 RNA 作为儿童肾横纹肌肉瘤的预后因素。

Immune-Related LncRNAs as Prognostic Factors for Pediatric Rhabdoid Tumor of the Kidney.

机构信息

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China.

Department of Pediatric Oncology, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China.

出版信息

Dis Markers. 2022 Jun 15;2022:4752184. doi: 10.1155/2022/4752184. eCollection 2022.

Abstract

BACKGROUND

Immune-related long noncoding RNAs (IrlncRNAs) are recognized as important prognostic factors in a variety of cancers, but thus far, their prognostic value in pediatric rhabdoid tumor of the kidney (pRTK) has not been reported. Here, we clarified the associations between IrlncRNAs and overall survival (OS) of pRTK patients and constructed a model to predict their prognosis.

METHODS

We accessed RNA sequencing data and corresponding clinical data of pRTK from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. An expression profile of immune-related genes (Irgenes) and lncRNAs of pRTK was extracted from the RNA sequencing data. IrlncRNAs were defined by co-expression analysis of lncRNAs and Irgenes. The limma R package was used to identify differential expression IrlncRNAs. Univariate and multivariate Cox regression analyses were conducted to build a prognostic IrlncRNAs model. The performance of this prognostic model was validated by multimethods, like ROC curve analysis.

RESULTS

A total of 1097 IrlncRNAs were defined. Univariate Cox regression analysis identified 7 IrlncRNAs (AC004791.2, AP003068.23, RP11-54O7.14, RP11-680F8.1, TBC1D3P1-DHX40P1, TUNAR, and XXbac-BPG308K3.5) and were significantly associated with OS. Multivariate regression analysis constructed the best prognostic model based on the expression of AC004791.2, AP003068.23, RP11-54O7.14, TBC1D3P1-DHX40P1, and TUNAR. According to the prognostic model, a risk score of each patient was calculated, and patients were divided into high-risk and low-risk groups accordingly. The survival time of low-risk patients was significantly better than high-risk patients ( < 0.001). Univariate (hazard ratio 1.098, 95% confidence interval 1.048-1.149, value <0.001) and multivariate (hazard ratio 1.095, 95% confidence interval 1.043-1.150, value <0.001) analyses confirmed that the prognostic model was reliable and independent in prediction of OS. Time-dependent ROC analysis showed that 1-year survival AUC of prognostic model, stage, age, and sex was 0.824, 0.673, 0.531, and 0.495, respectively, which suggested that the prognostic model was the best predictor of survival in pRTK patients.

CONCLUSIONS

The prognostic model based on 5 IrlncRNAs was robust and could better predict the survival of pRTK than other clinical factors. Additionally, the mechanism of regulation and action of prognosis-associated lncRNAs could provide new avenues for basic research to explore the mechanism of tumor initiation and development in order to prevent and treat pRTK.

摘要

背景

免疫相关长非编码 RNA(IrlncRNAs)已被认为是多种癌症的重要预后因素,但迄今为止,其在小儿肾横纹肌样瘤(pRTK)中的预后价值尚未报道。在这里,我们阐明了 IrlncRNAs 与 pRTK 患者总生存期(OS)之间的关联,并构建了一个预测其预后的模型。

方法

我们从治疗性应用研究生成有效治疗方法(TARGET)数据库中获取了 pRTK 的 RNA 测序数据和相应的临床数据。从 RNA 测序数据中提取了 pRTK 的免疫相关基因(Irgenes)和 lncRNAs 的表达谱。通过 lncRNAs 和 Irgenes 的共表达分析定义 IrlncRNAs。使用 limma R 包识别差异表达的 IrlncRNAs。使用单变量和多变量 Cox 回归分析构建预后 IrlncRNAs 模型。通过 ROC 曲线分析等多种方法验证该预后模型的性能。

结果

共定义了 1097 个 IrlncRNAs。单变量 Cox 回归分析确定了 7 个 IrlncRNAs(AC004791.2、AP003068.23、RP11-54O7.14、RP11-680F8.1、TBC1D3P1-DHX40P1、TUNAR 和 XXbac-BPG308K3.5)与 OS 显著相关。多变量回归分析基于 AC004791.2、AP003068.23、RP11-54O7.14、TBC1D3P1-DHX40P1 和 TUNAR 的表达构建了最佳预后模型。根据预后模型,计算每位患者的风险评分,并相应地将患者分为高风险和低风险组。低风险患者的生存时间明显优于高风险患者(<0.001)。单变量(风险比 1.098,95%置信区间 1.048-1.149, 值<0.001)和多变量(风险比 1.095,95%置信区间 1.043-1.150, 值<0.001)分析证实,该预后模型在预测 OS 方面是可靠和独立的。时间依赖性 ROC 分析显示,预后模型、分期、年龄和性别预测 1 年生存率的 AUC 分别为 0.824、0.673、0.531 和 0.495,这表明该预后模型是预测 pRTK 患者生存的最佳指标。

结论

基于 5 个 IrlncRNAs 的预后模型稳健,可较其他临床因素更好地预测 pRTK 的生存情况。此外,预后相关 lncRNAs 的调控和作用机制可为基础研究提供新途径,以探索肿瘤发生和发展的机制,从而预防和治疗 pRTK。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e12/9217527/d1a8be83d681/DM2022-4752184.001.jpg

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