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多发性骨髓瘤患者潜在预后长链非编码RNA的鉴定及其在预测生存中的验证

Potential prognostic long non-coding RNA identification and their validation in predicting survival of patients with multiple myeloma.

作者信息

Hu Ai-Xin, Huang Zhi-Yong, Zhang Lin, Shen Jian

机构信息

1 Department of Orthopedic Surgery, People's Hospital of Three Gorges University, Yichang, China.

2 PuAi Institute, Edong Healthcare Group, Huangshi Central Hospital, Huangshi, China.

出版信息

Tumour Biol. 2017 Apr;39(4):1010428317694563. doi: 10.1177/1010428317694563.

Abstract

Multiple myeloma, a typical hematological malignancy, is characterized by malignant proliferation of plasma cells. This study was to identify differently expressed long non-coding RNAs to predict the survival of patients with multiple myeloma efficiently. Gene expressing profiles of diagnosed patients with multiple myeloma, GSE24080 (559 samples) and GSE57317 (55 samples), were downloaded from Gene Expression Omnibus database. After processing, survival-related long non-coding RNAs were identified by Cox regression analysis. The prognosis of multiple myeloma patients with differently expressed long non-coding RNAs was predicted by Kaplan-Meier analysis. Meanwhile, stratified analysis was performed based on the concentrations of serum beta 2-microglobulin (S-beta 2m), albumin, and lactate dehydrogenase of multiple myeloma patients. Gene set enrichment analysis was performed to further explore the functions of identified long non-coding RNAs. A total of 176 long non-coding RNAs significantly related to the survival of multiple myeloma patients (p < 0.05) were identified. In dataset GSE24080 and GSE57317, there were 558 and 55 patients being clustered into two groups with significant differences, respectively. Stratified analysis indicated that prediction of the prognoses with these long non-coding RNAs was independent from other clinical phenotype of multiple myeloma. Gene set enrichment analysis-identified pathways of cell cycle, focal adhesion, and G2-M checkpoint were associated with these long non-coding RNAs. A total of 176 long non-coding RNAs, especially RP1-286D6.1, AC008875.2, MTMR9L, AC069360.2, and AL512791.1, were potential biomarkers to evaluate the prognosis of multiple myeloma patients. These long non-coding RNAs participated indispensably in many pathways associated to the development of multiple myeloma; however, the molecular mechanisms need to be further studied.

摘要

多发性骨髓瘤是一种典型的血液系统恶性肿瘤,其特征为浆细胞的恶性增殖。本研究旨在鉴定差异表达的长链非编码RNA,以有效预测多发性骨髓瘤患者的生存期。从基因表达综合数据库下载了已确诊的多发性骨髓瘤患者的基因表达谱GSE24080(559个样本)和GSE57317(55个样本)。经过处理后,通过Cox回归分析鉴定与生存相关的长链非编码RNA。采用Kaplan-Meier分析预测差异表达长链非编码RNA的多发性骨髓瘤患者的预后。同时,根据多发性骨髓瘤患者血清β2-微球蛋白(S-β2m)、白蛋白和乳酸脱氢酶的浓度进行分层分析。进行基因集富集分析以进一步探究所鉴定的长链非编码RNA的功能。共鉴定出176个与多发性骨髓瘤患者生存显著相关的长链非编码RNA(p < 0.05)。在数据集GSE24080和GSE57317中,分别有558例和55例患者被聚类为两组,差异显著。分层分析表明,这些长链非编码RNA对预后的预测独立于多发性骨髓瘤的其他临床表型。基因集富集分析鉴定出的细胞周期、粘着斑和G2-M检查点通路与这些长链非编码RNA相关。总共176个长链非编码RNA,尤其是RP1-286D6.1、AC008875.2、MTMR9L、AC069360.2和AL512791.1,是评估多发性骨髓瘤患者预后

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