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三阴性乳腺癌中用于预测预后和免疫治疗的炎症反应相关特征的开发与验证

Development and validation of an inflammatory response-related signature in triple negative breast cancer for predicting prognosis and immunotherapy.

作者信息

Guo Yangyang, Cen Kenan, Yang Shi, Mai Yifeng, Hong Kai

机构信息

Department of Thyroid and Breast Surgery, Ningbo First Hospital, Ningbo, Zhejiang, China.

Department of Geriatrics, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, Zhejiang, China.

出版信息

Front Oncol. 2023 Jun 15;13:1175000. doi: 10.3389/fonc.2023.1175000. eCollection 2023.

Abstract

BACKGROUND

Inflammation is one of the most important characteristics of tumor tissue. Signatures based on inflammatory response-related genes (IRGs) can predict prognosis and treatment response in a variety of tumors. However, the clear function of IRGs in the triple negative breast cancer (TNBC) still needs to be explored.

METHODS

IRGs clusters were discovered via consensus clustering, and the prognostic differentially expressed genes (DEGs) across clusters were utilized to develop a signature using a least absolute shrinkage and selection operator (LASSO). Verification analyses were conducted to show the robustness of the signature. The expression of risk genes was identified by RT-qPCR. Lastly, we formulated a nomogram to improve the clinical efficacy of our predictive tool.

RESULTS

The IRGs signature, comprised of four genes, was developed and was shown to be highly correlated with the prognoses of TNBC patients. In contrast with the performance of the other individual predictors, we discovered that the IRGs signature was remarkably superior. Also, the ImmuneScores were elevated in the low-risk group. The immune cell infiltration showed significant difference between the two groups, as did the expression of immune checkpoints.

CONCLUSION

The IRGs signature could act as a biomarker and provide a momentous reference for individual therapy of TNBC.

摘要

背景

炎症是肿瘤组织最重要的特征之一。基于炎症反应相关基因(IRGs)的特征可预测多种肿瘤的预后和治疗反应。然而,IRGs在三阴性乳腺癌(TNBC)中的具体功能仍有待探索。

方法

通过一致性聚类发现IRGs簇,并利用各簇间的预后差异表达基因(DEGs),采用最小绝对收缩和选择算子(LASSO)构建特征。进行验证分析以证明该特征的稳健性。通过RT-qPCR鉴定风险基因的表达。最后,我们制定了一个列线图以提高预测工具的临床疗效。

结果

构建了由四个基因组成的IRGs特征,该特征与TNBC患者的预后高度相关。与其他个体预测指标的表现相比,我们发现IRGs特征明显更优。此外,低风险组的免疫评分升高。两组之间的免疫细胞浸润以及免疫检查点的表达均存在显著差异。

结论

IRGs特征可作为一种生物标志物,为TNBC的个体化治疗提供重要参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eb6/10311032/93c346b1a703/fonc-13-1175000-g001.jpg

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