Integration of radiogenomic features for early prediction of pathological complete response in patients with triple-negative breast cancer and identification of potential therapeutic targets.
Integration of radiogenomic features for early prediction of pathological complete response in patients with triple-negative breast cancer and identification of potential therapeutic targets.
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整合放射基因组特征以早期预测三阴性乳腺癌患者的病理完全缓解并识别潜在的治疗靶点
DOI：
10.1186/s12967-022-03452-1
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发表时间：
2022-06-07
影响因子：
7.4
通讯作者：
Shao, Zhimin
中科院分区：
文献类型：
--
作者：
Zhang, Ying;You, Chao;Pei, Yuchen;Yang, Fan;Li, Daqiang;Jiang, Yi-zhou;Shao, Zhimin
关键词：
我们建立了一个放射基因组学模型来预测三阴性乳腺癌（TNBC）的病理完全缓解（pCR），并探讨了高频突变与耐药性之间的关系。从2018年4月至2019年9月，纳入了112例接受新辅助化疗的患者。我们将研究人群随机分为训练集和验证集（2：1的比例）。在基线和两个治疗周期后获得对比度增强的磁共振成像扫描，并用于提取定量放射组学特征，并使用光梯度增强机构建两个仅放射组学模型。通过结合从基线核心组织获得的变异等位基因频率特征，构建放射基因组学模型来预测pCR。此外，我们还探讨了复发性突变与耐药性之间的关系。两种仅放射学模型显示出相似的性能，AUC分别为0.71和0.73（p = 0.55）。在验证集中，放射基因组学模型的预测能力高于仅放射组学模型（p = 0.04），相应的AUC为0.87（0.73-0.91）。在比较pCR和非pCR群体的突变位点后，选择了两个高频突变。MED 23突变p.P394H在体外引起表阿霉素耐药（p < 0.01）。p.P394H细胞中γ-H2A.X、p-ATM和p-CHK 2的表达水平明显低于野生型细胞（p < 0.01）。在HR修复系统中，MED 23 p.P394H细胞的GFP阳性率高于野生型细胞（p < 0.01）。所提出的放射基因组学模型具有准确预测TNBC患者中的pCR的潜力。MED 23 p.P394H突变后的耐药可能通过p-ATM-γ-H2 A.X-p-CHK 2通路的调节而受到HR修复的影响。在线版本包含补充材料，可通过10.1186/s12967-022-03452-1获得。
We established a radiogenomic model to predict pathological complete response (pCR) in triple-negative breast cancer (TNBC) and explored the association between high-frequency mutations and drug resistance. From April 2018 to September 2019, 112 patients who had received neoadjuvant chemotherapy were included. We randomly split the study population into training and validation sets (2:1 ratio). Contrast-enhanced magnetic resonance imaging scans were obtained at baseline and after two cycles of treatment and were used to extract quantitative radiomic features and to construct two radiomics-only models using a light gradient boosting machine. By incorporating the variant allele frequency features obtained from baseline core tissues, a radiogenomic model was constructed to predict pCR. Additionally, we explored the association between recurrent mutations and drug resistance. The two radiomics-only models showed similar performance with AUCs of 0.71 and 0.73 (p = 0.55). The radiogenomic model had a higher predictive ability than the radiomics-only model in the validation set (p = 0.04), with a corresponding AUC of 0.87 (0.73–0.91). Two highly frequent mutations were selected after comparing the mutation sites of pCR and non-pCR populations. The MED23 mutation p.P394H caused epirubicin resistance in vitro (p < 0.01). The expression levels of γ-H2A.X, p-ATM and p-CHK2 in MED23 p.P394H cells were significantly lower than those in wild type cells (p < 0.01). In the HR repair system, the GFP positivity rate of MED23 p.P394H cells was higher than that in wild-type cells (p < 0.01). The proposed radiogenomic model has the potential to accurately predict pCR in TNBC patients. Epirubicin resistance after MED23 p.P394H mutation might be affected by HR repair through regulation of the p-ATM-γ-H2A.X-p-CHK2 pathway. The online version contains supplementary material available at 10.1186/s12967-022-03452-1.
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影响因子：
3.3
作者：
Ma, Mingming;Gan, Liangyu;Wang, Xiaoying
通讯作者：
Wang, Xiaoying
三阴性乳腺癌的基因组和转录组景观：亚型和治疗策略
影响因子：
50.3
作者：
Jiang, Yi-Zhou;Ma, Ding;Shao, Zhi-Ming
通讯作者：
Shao, Zhi-Ming
DOI：
10.1186/s13058-017-0846-1
发表时间：
2017-05-18
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Braman NM;Etesami M;Prasanna P;Dubchuk C;Gilmore H;Tiwari P;Plecha D;Madabhushi A
通讯作者：
Madabhushi A
影响因子：
51.1
作者：
Coudert, Bruno;Pierga, Jean-Yves;Berriolo-Riedinger, Alina
通讯作者：
Berriolo-Riedinger, Alina
影响因子：
3.9
作者：
Mireștean CC;Volovăț C;Iancu RI;Iancu DPT
通讯作者：
Iancu DPT