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基于化疗敏感性构建免疫相关基因的乳腺癌新型预后模型:一项化疗敏感性研究。

Immune-Related Genes to Construct a Novel Prognostic Model of Breast Cancer: A Chemosensitivity-Based Study.

机构信息

Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China.

Department of Obstetrics and Gynecology Ultrasound, Renmin Hospital of Wuhan University, Wuhan, China.

出版信息

Front Immunol. 2021 Oct 26;12:734745. doi: 10.3389/fimmu.2021.734745. eCollection 2021.

Abstract

Chemotherapy combined with surgery is effective for patients with breast cancer (BC). However, chemoresistance restricts the effectiveness of BC treatment. Immune microenvironmental changes are of pivotal importance for chemotherapy responses. Thus, we sought to construct and validate an immune prognostic model based on chemosensitivity status in BC. Here, immune-related and chemosensitivity-related genes were obtained from GSE25055. Then, univariate analysis was employed to identify prognostic-related gene pairs from the intersection of the two parts of the genes, and modified least absolute shrinkage and selection operator (LASSO) analysis was performed to build a prognostic model. Furthermore, we investigated the efficiency of this model from various perspectives, and further validation was performed using the Cancer Genome Atlas (TCGA) cohorts. We identified seven immune and chemosensitivity-related gene pairs and incorporated them into the Cox regression model. After multilevel validation, the risk model was found to be closely related to the survival rate, various clinical characteristics, tumor mutation burden (TMB) score, immune checkpoints, and response to chemotherapeutic drugs. In addition, the model was verified to exhibit predictive capacity as an independent factor over other candidate clinical features. Notably, the constructed nomogram was more accurate than any single factor. Altogether, the risk score model and the nomogram have potential predictive value and may have important practical implications.

摘要

化疗联合手术对乳腺癌(BC)患者有效。然而,化疗耐药限制了 BC 治疗的效果。免疫微环境的变化对化疗反应至关重要。因此,我们试图构建和验证一个基于 BC 化疗敏感性的免疫预后模型。在这里,我们从 GSE25055 中获取了免疫相关和化疗敏感性相关基因。然后,我们采用单变量分析从基因的两个部分的交集识别与预后相关的基因对,并进行改进的最小绝对收缩和选择算子(LASSO)分析,以构建预后模型。此外,我们从多个角度研究了该模型的效率,并使用癌症基因组图谱(TCGA)队列进行了进一步验证。我们确定了七个免疫和化疗敏感性相关基因对,并将其纳入 Cox 回归模型。经过多层次验证,该风险模型与生存率、各种临床特征、肿瘤突变负荷(TMB)评分、免疫检查点和对化疗药物的反应密切相关。此外,该模型被证明作为独立因素具有比其他候选临床特征更好的预测能力。值得注意的是,构建的列线图比任何单一因素都更准确。总之,风险评分模型和列线图具有潜在的预测价值,可能具有重要的实际意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b9f/8576363/414756aaf5a6/fimmu-12-734745-g001.jpg

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