基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Luminal androgen receptor subtype and tumor-infiltrating lymphocytes groups based on triple-negative breast cancer molecular subclassification.
Luminal androgen receptor subtype and tumor-infiltrating lymphocytes groups based on triple-negative breast cancer molecular subclassification.
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在既往研究中,我们建立了与 TNBC 分子亚型相关的三阴性乳腺癌(TNBC)亚型分类。本研究旨在全切片层面评估该分类的预测变量,并利用外部测试集验证模型性能,同时探索分类特征和基因组改变(包括基因组疤痕特征评分)。首先依据 AR Allred 评分(≥6 或 <6),将 TNBC 分为管腔雄激素受体(LAR)型和非 LAR 型。随后依据基质TIL(肿瘤浸润淋巴细胞)水平,将非 LAR 型进一步分为淋巴细胞丰富(LP,<20%)、中间型(LI,>20% 且 <60%)和淋巴细胞缺乏(LD,≥60%)组。该分类与测试集分子分类达到中等一致性。LAR 亚型的特征包括 PIK3CA 突变率较高、CD274(编码 PD-L1)和 PDCD1LG2(编码 PD-L2)缺失,以及同源重组缺陷(HRD)评分较低。非 LAR 型 LD-TIL 组则以 NOTCH2 和 MYC 扩增频率高、HRD 评分高为特征。
In our previous study, we developed a triple-negative breast cancer (TNBC) subtype classification that correlated with the TNBC molecular subclassification. In this study, we aimed to evaluate the predictor variables of this subtype classification on the whole slide and to validate the model's performance by using an external test set.
We explored the characteristics of this subtype classification and investigated genomic alterations, including genomic scar signature scores. First, TNBC was classified into the luminal androgen receptor (LAR) and non-luminal androgen receptor (non-LAR) subtypes based on the AR Allred score ( 6 and < 6, respectively). Then, the non-LAR subtype was further classified into the lymphocyte-predominant (LP), lymphocyte-intermediate (LI), and lymphocyte-depleted (LD) groups based on stromal tumor-infiltrating lymphocytes (TILs) (< 20%, > 20% but < 60%, and 60%, respectively).
This classification showed fair agreement with the molecular classification in the test set. The LAR subtype was characterized by a high rate of PIK3CA mutation, CD274 (encodes PD-L1) and PDCD1LG2 (encodes PD-L2) deletion, and a low homologous recombination deficiency (HRD) score. The non-LAR LD TIL group was characterized by a high frequency of NOTCH2 and MYC amplification and a high HRD score.
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