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
鉴定软骨素聚合因子作为预测乳腺癌免疫治疗应答的生物标志物：肿瘤微环境的生物信息学分析
英文原题：Identification of chondroitin polymerizing factor as a biomarker for predicting immunotherapy response in breast cancer: a bioinformatics analysis of tumor microenvironment.
查看英文原题
Identification of chondroitin polymerizing factor as a biomarker for predicting immunotherapy response in breast cancer: a bioinformatics analysis of tumor microenvironment.
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研究概要
这些数据表明，CHPF 有可能作为 BRCA 免疫治疗应答的预测因子。
中文摘要
背景
免疫检查点阻断（ICB）治疗为多种癌症带来显著临床获益，但许多患者仍无法从中获得持久疗效。肿瘤微环境（TME）由肿瘤细胞、基质细胞、免疫细胞和细胞外基质（ECM）构成，是决定临床结局和ICB应答的关键因素。本研究主要旨在将乳腺癌（BRCA）TME划分为不同亚型，以预测ICB应答，并揭示相关分子机制。
方法
从癌症基因组图谱（TCGA）数据库获取转录组特征及临床信息。采用基于表达数据估算恶性肿瘤间质和免疫细胞（ESTIMATE）算法分析免疫及基质细胞浸润，并以加权基因共表达网络分析（WGCNA）构建共表达网络。
结果
BRCA TME被分为四种不同亚型，该分类可用于预测TCGA-BRCA队列中的总生存期（OS）和免疫治疗疗效。研究发现软骨素聚合因子（CHPF）在免疫抑制性TME中发挥重要作用。从机制上看，CHPF水平与自然杀伤（NK）细胞、细胞毒性T淋巴细胞及CD8 T细胞浸润呈负相关，与癌相关成纤维细胞（CAF）、内皮细胞及单核细胞谱系浸润呈正相关。CHPF表达与PI3K/Akt活化、ECM失调及黏着斑信号通路相关；CHPF低水平则与抗肿瘤免疫应答显著相关。此外，无论ICB治疗前还是治疗期间，应答组CHPF水平都明显低于非应答组。CHPF高表达与ICB治疗后OS较差显著相关。
结论
这些数据表明，CHPF可能成为预测BRCA免疫治疗应答的生物标志物。
展开英文摘要原文
BACKGROUND
Immune checkpoint blockade (ICB) therapy offers remarkable clinical advantages for various cancers, but many patients still fail to receive sustained benefits from this treatment. Tumor microenvironment (TME), a multifaceted ecosystem composed of tumor cells, stromal cells, immune cells, and extracellular matrix (ECM), is critical in determining clinical outcomes and ICB response. The major aim of the study was to classify the breast cancer (BRCA) TME into distinct subtypes to predict ICB response, and to uncover the molecular mechanisms involved.
METHODS
Transcriptomic profiles and clinical information were obtained from The Cancer Genome Atlas (TCGA) database. The Estimation of STromal and Immune cells in MAlignant Tumours using Expression data (ESTIMATE) algorithm was employed for analyzing immune and stromal cell infiltration. Weighted gene co-expression network analysis (WGCNA) was used to build the co-expression network.
RESULTS
BRCA TME was classified into four distinct subtypes, and the TME classification can be used to predict overall survival (OS) and immunotherapy efficacy in the TCGA-BRCA cohort. Chondroitin polymerizing factor (CHPF) was identified as playing an important role in immunosuppressive TME. Mechanistically, CHPF levels were negatively associated with natural killer (NK) cell, cytotoxic T lymphocyte, and CD8 T cell infiltration and were positively associated with cancer-associated fibroblast (CAF), endothelial cell, and monocytic lineage infiltration. CHPF expression was correlated with the activation of PI3K/Akt, ECM dysregulation, and focal adhesion signaling pathways, while low CHPF level was significantly correlated with anti-tumor immune responses. Furthermore, CHPF levels were markedly elevated in the non-response group compared to the response group, regardless of pre- or on- ICB treatment. High CHPF expression was significantly correlated with poor OS after ICB treatment.
CONCLUSIONS
These data demonstrate that CHPF could potentially act as a predictor for immunotherapy response in BRCA.
论文信息
- 作者
- He Z、Xu Y、Wu C
- 第一作者单位
- Department of Dermatovenereology, Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.China
- 通讯作者单位
- Department of Urology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.China
- 期刊
- Translational cancer research2026 May 30
- 原文标识
- PubMed 42312195 · DOI 10.21037/tcr-2026-1-0221
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