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一种与同源重组缺陷相关的16基因特征用于三阴性乳腺癌患者的预后预测。

A 16-gene signature associated with homologous recombination deficiency for prognosis prediction in patients with triple-negative breast cancer.

作者信息

Wang Daodu, Shi Yifeng, Huang Hanyang, Zhao Qijiong, He Yongyue, Su Wenzhi

机构信息

Oncology Center, Shanwei Yihui Fund Hospital (Shanwei Second People's Hospital), Shanwei, 516600, China.

Department of General Surgery, Shanwei Yihui Fund Hospital (Shanwei Second People's Hospital), Shanwei, 516600, China.

出版信息

Open Med (Wars). 2022 May 11;17(1):882-896. doi: 10.1515/med-2022-0475. eCollection 2022.

Abstract

Homologous recombination deficiency (HRD) commonly occurs in breast cancer, which is the second cause of cancer death in women with a high rate of relapse and poor outcomes. Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Thus, we aim to develop a prognostic signature based on HRD expecting to help improve outcomes in TNBC. The Cancer Genome Atlas (TCGA)-TNBC cohort was divided into the training set and the testing set randomly. Sixteen genes were filtered from the prognostic HRD-associated genes to establish a prognostic model in the training set. Patients were divided into high-risk and low-risk groups based on the median value of the risk score. Prognosis analysis showed that the high-risk group was associated with a worse prognosis in the training set, the testing set, the entire TCGA-TNBC cohort, and the METABRIC-TNBC cohort. The time-dependent receiver operating characteristic curve showed that our model had very good accuracy in the prediction of 1-5-year overall survival in the TCGA-TNBC cohort. Besides, a comparison of the area under curve value and -index between our model and four published models showed that our model had the best predictive efficiency compared to other models. Subsequently, a nomogram was established. Finally, our finding also indicated that our model was associated with immunoregulation in TNBC and had the potential to be the target for TNBC treatment. Therefore, our findings not only provided a new strategy in the personalized prognosis management of TNBC but also offered new insight into precision treatment in TNBC.

摘要

同源重组缺陷(HRD)在乳腺癌中普遍存在,乳腺癌是女性癌症死亡的第二大原因,复发率高且预后较差。三阴性乳腺癌(TNBC)是最具侵袭性的乳腺癌亚型。因此,我们旨在基于HRD开发一种预后特征,期望有助于改善TNBC的预后。癌症基因组图谱(TCGA)-TNBC队列被随机分为训练集和测试集。从与预后相关的HRD基因中筛选出16个基因,在训练集中建立预后模型。根据风险评分的中位数将患者分为高风险组和低风险组。预后分析表明,在训练集、测试集、整个TCGA-TNBC队列和METABRIC-TNBC队列中,高风险组的预后较差。时间依赖性受试者工作特征曲线表明,我们的模型在预测TCGA-TNBC队列1至5年总生存率方面具有非常好的准确性。此外,将我们的模型与四个已发表的模型的曲线下面积值和C指数进行比较,结果表明我们的模型与其他模型相比具有最佳的预测效率。随后,建立了列线图。最后,我们的研究结果还表明,我们的模型与TNBC中的免疫调节相关,并且有可能成为TNBC治疗的靶点。因此,我们的研究结果不仅为TNBC的个性化预后管理提供了一种新策略,也为TNBC的精准治疗提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3de/9096232/c41d7cd8dc24/j_med-2022-0475-fig006.jpg

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