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
PDJ 扩增子在三阴性乳腺癌中
英文原题：PDJ amplicon in triple negative breast cancer.
查看英文原题
PDJ amplicon in triple negative breast cancer.
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中文摘要
9p24.1 染色体扩增靶向 PD-L1、PD-L2 和 JAK2（PDJ 扩增子）存在于三阴性乳腺癌（TNBC）的亚群中，并与不良临床结局相关。
然而，采用不同方法检测感兴趣样本的研究中，PDJ+ TNBC 的患病率差异很大。为了严格评估 PDJ 扩增子在 TNBC 中的患病率、其预后价值以及是否因化疗而富集，我们检测了 360 例 TNBC 样本，包括 74 例来自新辅助治疗患者的手术切除标本，以及包含 31 例非裔美国女性病例和 255 例切除的非转移性病例的组织微阵列（TMA），采用针对 9p24.1 PDJ 扩增子、9q24.3 和 9q34.1 的 3 色荧光原位杂交（FISH）检测。平均 PDJ 信号 > 4.5 拷贝，且 PDJ/9q24 ≥ 2 和/或 PDJ/9q34.1 ≥ 2 的样本判定为扩增（PDJ+）。相关性分析包括 TNBC 中TIL（肿瘤浸润淋巴细胞）（TILs）与 PDJ 扩增子的关联。
此外，我们研究了 PDJ+ 和 PDJ- TNBC 中 PDJ 扩增子的瘤内拷贝数。从患者（n = 6）可获得匹配的新辅助治疗前和治疗后活检，以评估治疗对 PDJ 状态的影响。
我们的研究提供了 TNBC 中 PDJ 扩增子的患病率、分布和临床相关性的严格分析。
展开英文摘要原文
Amplification of chromosome 9p24. 1 targeting PD-L1, PD-L2, and JAK2 (PDJ amplicon) is present in subsets of triple negative breast cancers (TNBCs) and is associated with poor clinical outcomes.
However, the prevalence of PDJ+ TNBCs varies extensively across studies applying different methods for interrogating samples of interest. To rigorously assess the prevalence of PDJ amplicons in TNBC, its prognostic value and whether it is enriched by chemotherapy, we interrogated 360 TNBC samples including 74 surgical resections from patients treated in the neoadjuvant setting, and tissue microarrays (TMAs) with 31 cases from African American women and 255 resected non-metastatic cases, with a 3 color fluorescence in situ hybridization (FISH) assay targeting the 9p24.
1 PDJ amplicon, 9q24. 3, and 9q34. 1. Samples with mean PDJ signal of > 4. 5 copies, and ratios of PDJ/9q24 ≥ 2 and/or PDJ/9q34. 1 ≥ 2 were called amplified (PDJ+). Correlative analyses included the association of tumor infiltrating lymphocytes (TILs) with PDJ amplicons in TNBCs.
In addition, we investigated intratumor copy number of PDJ amplicons in PDJ+ and PDJ- TNBCs. Matched pre- and post-neoadjuvant treatment biopsies were available from patients (n = 6) to evaluate the effects of therapy on PDJ status.
Our study provides a rigorous analysis of the prevalence, distribution, and clinical correlatives of the PDJ amplicon in TNBC.
论文信息
- 作者
- Roesler AS、Malasi S、Koslosky L、Hartmayer P、Naab TJ、Carter JM、Zahrieh D、Hillman D
- 第一作者单位
- Department of Research, Mayo Clinic in Arizona, Scottsdale, AZ, USA.United States
- 通讯作者单位
- Department of Research, Mayo Clinic in Arizona, Scottsdale, AZ, USA. barrett.michael@mayo.edu.United States
- 文献类型
- 美国 NIH 资助研究 · 非美国政府资助研究
- 期刊
- Scientific reports2023 Jan 12
- 原文标识
- PubMed 36635351 · DOI 10.1038/s41598-023-27887-8
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