As a novel prognostic model for breast cancer, the identification and validation of telomere-related long noncoding RNA signatures

IF 2.5 3区 医学 Q3 ONCOLOGY
Wei Zhao, Beibei Li, Mingxiang Zhang, Peiyao Zhou, Yongyun Zhu
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Abstract

Telomeres are a critical component of chromosome integrity and are essential to the development of cancer and cellular senescence. The regulation of breast cancer by telomere-associated lncRNAs is not fully known, though. The goals of this study were to describe predictive telomere-related LncRNAs (TRL) in breast cancer and look into any possible biological roles for these RNAs. We obtained RNA-seq data, pertinent clinical data, and a list of telomere-associated genes from the cancer genome atlas and telomere gene database, respectively. We subjected differentially expressed TRLs to co-expression analysis and univariate Cox analysis to identify a prognostic TRL. Using LASSO regression analysis, we built a prognostic model with 14 TRLs. The accuracy of the model’s prognostic predictions was evaluated through the utilization of Kaplan-Meier (K-M) analysis as well as receiver operating characteristic (ROC) curve analysis. Additionally, immunological infiltration and immune drug prediction were done using this model. Patients with breast cancer were divided into two subgroups using cluster analysis, with the latter analyzed further for variations in response to immunotherapy, immune infiltration, and overall survival, and finally, the expression of 14-LncRNAs was validated by RT-PCR. We developed a risk model for the 14-TRL, and we used ROC curves to demonstrate how accurate the model is. The model may be a standalone prognostic predictor for patients with breast cancer, according to COX regression analysis. The immune infiltration and immunotherapy results indicated that the high-risk group had a low level of PD-1 sensitivity and a high number of macrophages infiltrating. In addition, we’ve discovered a number of small-molecule medicines with considerable for use in treating high-risk groups. The cluster 2 subtype showed the highest immune infiltration, the highest immune checkpoint expression, and the worst prognosis among the two subtypes defined by cluster analysis, which requires more attention and treatment. As a possible biomarker, the proposed 14-TRL signature could be utilized to evaluate clinical outcomes and treatment efficacy in breast cancer patients.
作为乳腺癌的新型预后模型,端粒相关长非编码 RNA 特征的识别和验证
端粒是染色体完整性的重要组成部分,对癌症的发展和细胞衰老至关重要。不过,端粒相关lncRNA对乳腺癌的调控作用还不完全清楚。本研究的目标是描述乳腺癌中的预测性端粒相关LncRNA(TRL),并研究这些RNA可能发挥的生物学作用。我们分别从癌症基因组图谱和端粒基因数据库中获得了RNA-seq数据、相关临床数据和端粒相关基因列表。我们对差异表达的端粒相关基因进行了共表达分析和单变量考克斯分析,以确定预后端粒相关基因。通过LASSO回归分析,我们建立了一个包含14个TRL的预后模型。通过卡普兰-梅耶(K-M)分析和接收者操作特征曲线(ROC)分析,评估了模型预后预测的准确性。此外,还利用该模型进行了免疫浸润和免疫药物预测。利用聚类分析将乳腺癌患者分为两个亚组,并进一步分析后者对免疫疗法的反应、免疫浸润和总生存期的变化,最后通过 RT-PCR 验证了 14-LncRNAs 的表达。我们为14-TRL建立了一个风险模型,并使用ROC曲线来证明该模型的准确性。根据 COX 回归分析,该模型可作为乳腺癌患者的独立预后预测指标。免疫浸润和免疫治疗结果表明,高风险组的 PD-1 敏感度低,巨噬细胞浸润数量多。此外,我们还发现了一些可用于治疗高危人群的小分子药物。在聚类分析所定义的两种亚型中,聚类 2 亚型的免疫浸润程度最高,免疫检查点表达量最高,预后最差,需要更多的关注和治疗。作为一种可能的生物标记物,所提出的14-TRL特征可用于评估乳腺癌患者的临床预后和治疗效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.70
自引率
15.60%
发文量
362
审稿时长
3 months
期刊介绍: World Journal of Surgical Oncology publishes articles related to surgical oncology and its allied subjects, such as epidemiology, cancer research, biomarkers, prevention, pathology, radiology, cancer treatment, clinical trials, multimodality treatment and molecular biology. Emphasis is placed on original research articles. The journal also publishes significant clinical case reports, as well as balanced and timely reviews on selected topics. Oncology is a multidisciplinary super-speciality of which surgical oncology forms an integral component, especially with solid tumors. Surgical oncologists around the world are involved in research extending from detecting the mechanisms underlying the causation of cancer, to its treatment and prevention. The role of a surgical oncologist extends across the whole continuum of care. With continued developments in diagnosis and treatment, the role of a surgical oncologist is ever-changing. Hence, World Journal of Surgical Oncology aims to keep readers abreast with latest developments that will ultimately influence the work of surgical oncologists.
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