Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, Liaoning Province, 110004, P.R. China.
BMC Cancer. 2022 Jun 8;22(1):633. doi: 10.1186/s12885-022-09591-4.
BACKGROUND: Long non-coding RNAs (lncRNAs) play an important role in angiogenesis, immune response, inflammatory response and tumor development and metastasis. m6 A (N6-methyladenosine) is one of the most common RNA modifications in eukaryotes. The aim of our research was to investigate the potential prognostic value of m6A-related lncRNAs in ovarian cancer (OC). METHODS: The data we need for our research was downloaded from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. Pearson correlation analysis between 21 m6A regulators and lncRNAs was performed to identify m6A-related lncRNAs. Univariate Cox regression analysis was implemented to screen for lncRNAs with prognostic value. A least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression analyses was used to further reduct the lncRNAs with prognostic value and construct a m6A-related lncRNAs signature for predicting the prognosis of OC patients. RESULTS: Two hundred seventy-five m6A-related lncRNAs were obtained using pearson correlation analysis. 29 m6A-related lncRNAs with prognostic value was selected through univariate Cox regression analysis. Then, a seven m6A-related lncRNAs signature was identified by LASSO Cox regression. Each patient obtained a riskscore through multivariate Cox regression analyses and the patients were classified into high-and low-risk group using the median riskscore as a cutoff. Kaplan-Meier curve revealed that the patients in high-risk group have poor outcome. The receiver operating characteristic curve revealed that the predictive potential of the m6A-related lncRNAs signature for OC was powerful. The predictive potential of the m6A-related lncRNAs signature was successfully validated in the GSE9891, GSE26193 datasets and our clinical specimens. Multivariate analyses suggested that the m6A-related lncRNAs signature was an independent prognostic factor for OC patients. Moreover, a nomogram based on the expression level of the seven m6A-related lncRNAs was established to predict survival rate of patients with OC. Finally, a competing endogenous RNA (ceRNA) network associated with the seven m6A-related lncRNAs was constructed to understand the possible mechanisms of the m6A-related lncRNAs involed in the progression of OC. CONCLUSIONS: In conclusion, our research revealed that the m6A-related lncRNAs may affect the prognosis of OC patients and identified a seven m6A-related lncRNAs signature to predict the prognosis of OC patients.
背景:长链非编码 RNA(lncRNA)在血管生成、免疫反应、炎症反应和肿瘤发展及转移中发挥重要作用。m6A(N6-甲基腺苷)是真核生物中最常见的 RNA 修饰之一。本研究旨在探讨 m6A 相关 lncRNA 在卵巢癌(OC)中的潜在预后价值。
方法:本研究所需的数据从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)下载。采用 Pearson 相关性分析鉴定 21 个 m6A 调控因子与 lncRNA 之间的关系,筛选 m6A 相关 lncRNA。采用单因素 Cox 回归分析筛选具有预后价值的 lncRNA。采用最小绝对收缩和选择算子(LASSO)Cox 回归及多因素 Cox 回归分析进一步减少具有预后价值的 lncRNA,并构建 m6A 相关 lncRNA 预测 OC 患者预后的模型。
结果:采用 Pearson 相关性分析获得 275 个 m6A 相关 lncRNA。单因素 Cox 回归分析筛选出 29 个具有预后价值的 m6A 相关 lncRNA。然后,采用 LASSO Cox 回归分析构建了一个由 7 个 m6A 相关 lncRNA 组成的signature。通过多因素 Cox 回归分析为每位患者计算风险评分,以中位数作为截断值将患者分为高风险组和低风险组。Kaplan-Meier 曲线显示,高风险组患者预后不良。受试者工作特征曲线表明,m6A 相关 lncRNA 预测 OC 的潜在价值较高。该 m6A 相关 lncRNA 预测 OC 的模型在 GSE9891、GSE26193 数据集和临床标本中得到了验证。多因素分析表明,m6A 相关 lncRNA 预测 OC 患者预后的独立危险因素。此外,基于 7 个 m6A 相关 lncRNA 的表达水平建立了预测 OC 患者生存率的列线图。最后,构建了一个与 7 个 m6A 相关 lncRNA 相关的竞争性内源性 RNA(ceRNA)网络,以了解 m6A 相关 lncRNA 参与 OC 进展的可能机制。
结论:综上所述,本研究表明 m6A 相关 lncRNA 可能影响 OC 患者的预后,并确定了一个 7 个 m6A 相关 lncRNA 预测 OC 患者预后的 signature。
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