基于髓源性抑制细胞相关lncrna的预后特征的鉴定和外部验证，以评估浸润性乳腺癌的生存预后和治疗效果

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports Pub Date : 2025-09-16 DOI:10.1016/j.bbrep.2025.102261

Yun Zhong , Tong Mu , Shunyao Zhang , Yuan Xiang , Lei Xie , Wenxiong Zhang , Kang Wang

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引用次数: 0

摘要

髓源性抑制细胞（myeloid-derived suppressor cells, MDSCs）起源于造血组织，在肿瘤相关免疫过程中起着重要作用。然而，它们与长链非编码rna （lncRNAs）和乳腺癌的关系仍不完全清楚。在这项研究中，我们引入了mdscs相关的lncrna作为新的预后生物标志物来评估浸润性乳腺癌（BRCA）患者的预后。方法从TCGA数据库中获取BRCA病例的临床和基因组信息。发现了预测指标，并对其可靠性进行了全面验证。在基于应用程序的验证后，开发了临床有用的nomogram。其他研究包括功能分析、TMB评估、TME谱分析、免疫治疗疗效预测、药物敏感性测试以及靶点识别。采用反转录定量PCR法检测长链非编码RNA的表达。结果纳入8种mdscs相关lncrna的风险分层模型能有效预测患者预后。Kaplan-Meier （K-M）生存分析清楚地表明，高危患者的预后差得多（p < 0.001）。nomogram能准确预测总生存期（OS）。功能富集分析显示，与上皮细胞相关的通路在高风险患者中显示出活性。肿瘤微环境的特征显示，在那些被归类为低风险的患者中，免疫细胞的存在增加。相反，风险越大的个体表现出更高的肿瘤突变负担。TIDE和IPS分析显示低危BRCA亚组的免疫治疗反应性较好。在47种IC50差异显著的药物中，Ribociclib、PD173074、KU-55933、NU7441和nutlin-3a在低危组的IC50值较低，而拉帕替尼在高危组的IC50值较高。并预测了10种潜在的高危患者治疗药物及其靶点。RT-qPCR验证证实了模型的稳健性。我们成功验证了一种新的mdscs相关lncrna分子标记模型，为预测BRCA病例的预后和指导治疗决策提供了重要的见解。

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Identification and external validation of a prognostic signature based on myeloid-derived suppressor cells-related LncRNAs to evaluate survival prognosis and treatment efficacy in invasive breast carcinoma

Background

Originating in the hematopoietic tissue, myeloid-derived suppressor cells (MDSCs) significantly contribute to tumor-related immunological processes. However, their relationship with long noncoding RNAs (lncRNAs) and breast cancer remains incompletely understood. In this study, we introduced MDSCs-associated lncRNAs as novel prognostic biomarkers to assess outcomes in patients with invasive breast carcinoma (BRCA).

Methods

Information regarding BRCA cases, including clinical and genomic details, was obtained from the TCGA repository. Predictive indicators were discovered, and their reliability underwent thorough verification. A clinically useful nomogram was developed following application-based validation. Additional investigations encompassed functional analysis, TMB assessment, TME profiling, immunotherapy efficacy forecasting, and drug sensitivity testing along with target identification. Long non-coding RNA expression was measured using reverse transcription quantitative PCR.

Results

A risk stratification model incorporating eight MDSCs-related lncRNAs effectively predicted patient outcomes. Kaplan-Meier (K-M) survival analysis clearly indicated a much worse prognosis among patients classified as high-risk (p < 0.001). The nomogram accurately forecasted overall survival (OS). Analysis of functional enrichment revealed that pathways associated with epithelial cells showed activity among patients at higher risk. Characterization of the tumor microenvironment showed increased immune cell presence in those classified as low-risk. Conversely, individuals with greater risk displayed higher tumor mutational burden. TIDE and IPS analyses indicated superior immunotherapy responsiveness in the low-risk BRCA subgroup. Among 47 drugs with notable IC50 variations, Ribociclib, PD173074, KU-55933, NU7441, and nutlin-3a exhibited lower IC50 values within the low-risk group, whereas Lapatinib demonstrated greater efficacy among the high-risk group. Moreover, 10 potential therapeutic agents and their targets were predicted for high-risk patients. RT-qPCR validation confirmed the robustness of the model.

Conclusions

We successfully verified a new model of molecular markers of MDSCs-related lncRNAs, offering critical insights for predicting outcomes and guiding therapeutic decisions in BRCA cases.

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来源期刊

Biochemistry and Biophysics Reports Biochemistry, Genetics and Molecular Biology-Biophysics

CiteScore

4.60

自引率

0.00%

发文量

191

审稿时长

59 days

期刊介绍： Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.