RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
染色体区带 13q14.2 缺失调控乳腺癌发病机制与药物反应
英文原题：Loss of chromosome cytoband 13q14.2 orchestrates breast cancer pathogenesis and drug response.
查看英文原题
Loss of chromosome cytoband 13q14.2 orchestrates breast cancer pathogenesis and drug response.
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中文摘要
乳腺癌（BCa）是一项重大全球健康挑战。乳腺癌基因组常存在广泛体细胞拷贝数改变（CNA），包括增益/扩增和缺失/缺损。这些CNA显著影响肿瘤发生发展、药物应答及患者生存，但单个CNA的作用大多尚不清楚。研究者确定染色体13q14.2缺失是乳腺癌中的关键CNA；视亚型不同，该缺失可见于多达63%的患者，并与生存不良相关。通过多组学和体外分析，研究揭示13q14.2缺失具有矛盾性作用：一方面促进癌细胞细胞周期通路及促凋亡通路，另一方面与肿瘤微环境中NK细胞和巨噬细胞数量增加相关。值得注意的是，13q14.2缺失可使乳腺癌在体外及患者来源异种移植模型中对BCL2抑制剂更敏感。因此，13q14.2缺失可作为乳腺癌预后和治疗的生物标志物，有望改善患者结局。
展开英文摘要原文
Breast cancer (BCa) is a major global health challenge. The BCa genome often carries extensive somatic copy number alterations (CNAs), including gains/amplifications and losses/deletions. These CNAs significantly affect tumor development, drug response and patient survival.
However, how individual CNAs contribute is mostly elusive. We identified loss of chromosome 13q14. 2 as a key CNA in BCa, occurring in up to 63% of patients, depending on the subtype, and correlating with poor survival. Through multi-omics and in vitro analyses, we uncover a paradoxical role of 13q14. 2 loss, promoting both cell cycle and pro-apoptotic pathways in cancer cells, while also associating with increased NK cell and macrophage populations in the tumor microenvironment.
Notably, 13q14. 2 loss increases BCa susceptibility to BCL2 inhibitors, both in vitro and in patient-derived xenografts.
Thus, 13q14. 2 loss could serve as a biomarker for BCa prognosis and treatment, potentially improving outcomes for BCa patients.
论文信息
- 作者
- Shahrouzi P、Azimzade Y、Brankiewicz-Kopcinska W、Bhatia S、Kunke D、Richard D、Tekpli X、Kristensen VN
- 第一作者单位
- Department of Medical Genetics, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo and Oslo University Hospital, Oslo, Norway. parastoo.shahrouzi@medisin.uio.no.Norway
- 通讯作者单位
- Department of Medical Genetics, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo and Oslo University Hospital, Oslo, Norway. pascal.duijf@unisa.edu.au.Norway
- 期刊
- Breast cancer research : BCR2024 Nov 27
- 原文标识
- PubMed 39605038 · DOI 10.1186/s13058-024-01924-4
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