同源重组缺乏反映了乳腺癌患者的异质性和监测治疗反应。

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2023-11-23 DOI:10.1002/jgm.3637
Quanyi Long, Yunfei Wang, Hongjiang Li
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引用次数: 0

摘要

背景:在乳腺癌中,同源重组缺陷(HRD)是一种常见的致癌机制。根据HRD生物标志物对BC进行分类,为BC分子特征、病理特征和治疗反应的鉴别建立平台具有重要意义。方法:共收集109个HRD基因,采用单因素Cox回归分析筛选预后基因,构建共识矩阵确定BC亚型。采用Limma包筛选差异表达基因(differential expressed genes, DEGs),采用随机森林分析法筛选,建立模型分析BC患者对不同药物的免疫治疗反应、敏感性及预后。结果:109个HRD基因中有13个是BC的预后基因,根据表达情况将BC分为两个亚组。第1类患者的生存结果明显落后,适应性免疫评分明显高于第2类患者。通过随机森林分析确定了6个基因作为建立模型的因子。该模型提供了一个称为风险评分的预测,该预测对62种药物的BC预后、免疫治疗反应和IC50值有显著的分层效应。结论:在本研究中,成功鉴定了两种HRD亚型BC,并确定了其突变和免疫学特征。建立了基于HRD亚型差异基因的模型,该模型可作为预测BC预后、免疫治疗反应和药物敏感性的潜在指标。
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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Homologous recombination deficiency reflects the heterogeneity and monitoring treatment response for patients with breast cancer

Background

In breast cancer (BC), homologous recombination defect (HRD) is a common carcinogenic mechanism. It is meaningful to classify BC according to HRD biomarkers and to develop a platform for identifying BC molecular features, pathological features and therapeutic responses.

Methods

In total, 109 HRD genes were collected and screened by univariate Cox regression analysis to determine the prognostic genes, which were used to construct a consensus matrix to identify BC subtype. Differentially expressed genes (DEGs) were filtered by the Limma package and screened by random forest analysis to build a model to analyze the immunotherapy response and sensitivity and prognosis of patients suffering from BC to different drugs.

Results

Thirteen out of 109 HRD genes were prognostic genes of BC, and BC was classified into two subgroups based on their expression. Cluster 1 had a significantly backward survival outcome and a significantly higher adaptive immunity score relative to cluster 2. Six genes were identified by random forest analysis as factors for developing the model. The model provided a prediction called risk score, which showed a significant stratification effect on BC prognosis, immunotherapy response and IC50 values of 62 drugs.

Conclusions

In the present study, two HRD subtypes of BC were successfully identified, for which mutation and immunological features were determined. A model based on differential genes of HRD subtypes was established, which was a potential predictor of prognosis, immunotherapy response and drug sensitivity of BC.

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7.20
自引率
4.30%
发文量
567
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