A CTL/M2 macrophage-related four-gene signature predicting metastasis-free survival in triple-negative breast cancer treated with adjuvant radiotherapy
A CTL/M2 macrophage-related four-gene signature predicting metastasis-free survival in triple-negative breast cancer treated with adjuvant radiotherapy
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与 CTL/M2 巨噬细胞相关的四基因特征预测接受辅助放疗的三阴性乳腺癌的无转移生存期
DOI：
10.1007/s10549-021-06379-1
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Dong Wang
中科院分区：
文献类型：
--
作者：
Yunfei Ye;Jungang Ma;Qin Zhang;Kai Xiong;Zhimin Zhang;Chuan Chen;He Xiao;Dong Wang
PurposeThis研究的目的是开发和验证一个预后模型的无转移生存期（MFS）的基础上，可能与细胞毒性T淋巴细胞（CTL）和M2巨噬细胞在功能上相互作用的基因与三阴性乳腺癌（TNBC）谁经历了辅助radiotherapy.MethodsThe转录和表型的TNBC和其他乳腺癌亚型的档案从基因表达综合（GEO）下载。通过CIBERSORTx或MCP计数器评估浸润的免疫细胞的丰度。使用GSE 58812中的最小绝对收缩和选择算子（LASSO）开发了加权线性模型，即MFS评分（SMFS），并在GSE 2034和GSE 12276中进行了验证。SMFS的生物学意义进行了探讨，通过评估其与TNBC分子亚型和其他放射敏感性或免疫相关的signatures.ResultsA模型组成的PCDH 12/ELP 3，PCDH 12/MSRA，和FAM 160 B2/MSRA基因表达比例与非零系数最终选择LASSO开发使用GSE 58812。在GSE 2034（辅助放疗治疗）中，SMFS与TNBC患者的MFS显著相关（风险比（HR）= 8.767，95%置信区间（CI）1.856- 41.408，P = 0.006），在较小程度上，非TNBC患者的SMFS与MFS显著相关（HR = 2.888，95% CI 1.076- 7.750，P = 0.035）。而亚型（TNBC vs non-TNBC）与SMFS的交互作用有显著性（P交互作用= 0.081）。相比之下，在GSE 12276（无放疗治疗）中，TNBC患者（P= 0.499）或非TNBC患者（P= 0.536）的SMFS与MFS均无显著相关性。在四种TNBC分子亚型中，c1和c4亚型表现出比c2和c3亚型更高的CTL浸润和更低的SMFS值。此外，SMFS与内皮细胞丰度呈正相关（r= 0.413，P < 0.001）。结论该模型可用于预测TNBC患者辅助放疗后的MFS，SMFS可作为肿瘤免疫抑制的一个指标。
PurposeThis study aimed to develop and validate a prognostic model for metastasis-free survival (MFS) based on genes that may functionally interact with cytotoxic T lymphocytes (CTLs) and M2 macrophages in patients with triple-negative breast cancer (TNBC) who underwent adjuvant radiotherapy.MethodsThe transcriptional and phenotypic profiles of TNBC and other breast cancer subtypes were downloaded from gene expression omnibus (GEO). The abundance of infiltrated immune cells was evaluated through CIBERSORTx or MCP-counter. A weighted linear model, the score for MFS (SMFS), was developed using the least absolute shrinkage and selection operator (LASSO) in GSE58812 and validated in GSE2034 and GSE12276. The biological implication of the SMFS was explored by evaluating its associations with TNBC molecular subtypes and other radiosensitivity- or immune-related signatures.ResultsA model consisting of the PCDH12/ELP3, PCDH12/MSRA, and FAM160B2/MSRA gene expression ratios with non-zero coefficients finally selected by LASSO was developed using GSE58812. In GSE2034 (treatment with adjuvant radiotherapy), the SMFS was significantly associated with MFS in TNBC patients (hazard ratio (HR) = 8.767, 95% confidence interval (CI) 1.856–41.408,P= 0.006) and, to a lesser extent, in non-TNBC patients (HR = 2.888, 95% CI 1.076–7.750,P= 0.035). However, the interaction of subtype (TNBC vs non-TNBC) and the SMFS tended to be significant (Pinteraction= 0.081). In contrast, the SMFS was not significantly associated with MFS in either TNBC patients (P= 0.499) or non-TNBC patients (P= 0.536) in GSE12276 (treatment without radiotherapy). Among the four TNBC molecular subtypes, the c1 and c4 subtypes exhibited higher CTL infiltration and lower SMFS values than the c2 and c3 subtypes. In addition, the SMFS was positively correlated with the abundance of endothelial cells (r= 0.413,P< 0.001).ConclusionThe proposed model has the potential to predict MFS in TNBC patients after adjuvant radiotherapy, and the SMFS may represent a measurement of tumor immune suppression.
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影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
DOI：
10.1016/j.ejca.2017.08.001
发表时间：
2017-10
期刊：
European journal of cancer (Oxford, England : 1990)
影响因子：
--
作者：
Strom T;Harrison LB;Giuliano AR;Schell MJ;Eschrich SA;Berglund A;Fulp W;Thapa R;Coppola D;Kim S;Frakes J;Foekens J;Mulé JJ;Torres-Roca JF
通讯作者：
Torres-Roca JF
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影响因子：
5.8
作者：
Xu, Taosheng;Thuc Duy Le;Li, Jiuyong
通讯作者：
Li, Jiuyong
影响因子：
168.9
作者：
Denkert, Carsten;Liedtke, Cornelia;von Minckwitz, Gunter
通讯作者：
von Minckwitz, Gunter
影响因子：
37.3
作者：
Ren B;Cui M;Yang G;Wang H;Feng M;You L;Zhao Y
通讯作者：
Zhao Y