Establishment of a Prognostic Necroptosis-Related lncRNA Signature in Ovarian Cancer.

IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Combinatorial chemistry & high throughput screening Pub Date : 2025-01-07 DOI:10.2174/0113862073339602241028095015
Hui Xu, Meng Li, Wen-Lan Qiao, Tian Hua
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Abstract

Introduction: Ovarian Cancer (OC) was known for its high mortality rate among gynecological malignancies, often resulting in a poor prognosis. This study sought to identify prognostic necroptosis-related long non-coding RNAs (lncRNAs) (NRlncRNAs) with prognostic potential and to construct a reliable risk prediction model for OC patients.

Method: The transcriptome and clinic data were sourced from TCGA and GTEx databases. Initially, NRlncRNAs were discovered by assessing gene correlations and evaluating differences in gene expression. Subsequently, Cox regression and LASSO methods were employed to develop the NRlncRNAs risk model, which was further validated through survival analysis, ROC curves, Cox regression, and nomograms across both the test and entire datasets.

Results: Multivariate Cox analysis revealed that the risk score based on 14 NRlncRNAs can independently predict the prognosis of OC. The low-risk group demonstrated significantly higher immune cell infiltration scores and lower tumor immune dysfunction, exclusion, and TIDE scores, as well as an increased number of neoantigens and higher TMB. Notably, the low-risk group also exhibited an elevated HRD score.

Conclusion: The model's predictive accuracy was further substantiated through ROC analysis, showing superior performance compared to many existing models.Finally, the expression levels of 14 NRlncRNAs were confirmed using the qRT-PCR in two OC cell lines. These findings suggested that the NRlncRNAs risk model could serve as a more precise indicator for forecasting immune response and outcomes of targeted treatments in OC.

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卵巢癌预后坏死相关lncRNA信号的建立。
引言:卵巢癌(OC)是妇科恶性肿瘤中死亡率高的一种,往往导致预后不良。本研究旨在鉴定具有预后潜力的与坏死相关的长链非编码rna (lncRNAs) (NRlncRNAs),并为OC患者构建可靠的风险预测模型。方法:转录组和临床资料来源于TCGA和GTEx数据库。最初,NRlncRNAs是通过评估基因相关性和评估基因表达差异发现的。随后,采用Cox回归和LASSO方法建立NRlncRNAs风险模型,并通过生存分析、ROC曲线、Cox回归和norm图在测试和整个数据集上进行进一步验证。结果:多因素Cox分析显示,基于14种nrlncrna的风险评分能够独立预测OC的预后。低危组免疫细胞浸润评分明显升高,肿瘤免疫功能障碍、排斥和TIDE评分明显降低,新抗原数量增加,TMB升高。值得注意的是,低风险组也表现出较高的HRD评分。结论:通过ROC分析,进一步证实了模型的预测准确性,与现有的许多模型相比,表现出优越的性能。最后,利用qRT-PCR技术在2株OC细胞株中确认了14个nrlncrna的表达水平。这些发现表明,NRlncRNAs风险模型可以作为预测OC患者免疫反应和靶向治疗结果的更精确指标。
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来源期刊
CiteScore
3.10
自引率
5.60%
发文量
327
审稿时长
7.5 months
期刊介绍: Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal: Target identification and validation Assay design, development, miniaturization and comparison High throughput/high content/in silico screening and associated technologies Label-free detection technologies and applications Stem cell technologies Biomarkers ADMET/PK/PD methodologies and screening Probe discovery and development, hit to lead optimization Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) Chemical library design and chemical diversity Chemo/bio-informatics, data mining Compound management Pharmacognosy Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products) Natural Product Analytical Studies Bipharmaceutical studies of Natural products Drug repurposing Data management and statistical analysis Laboratory automation, robotics, microfluidics, signal detection technologies Current & Future Institutional Research Profile Technology transfer, legal and licensing issues Patents.
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