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CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
一种基于上皮-间质转化相关基因的新型预后特征，用于乳腺癌的预后和免疫状态
英文原题：A novel prognostic signature based on epithelial-mesenchymal transition-associated genes for the prognosis and immune status in breast cancer.
查看英文原题
A novel prognostic signature based on epithelial-mesenchymal transition-associated genes for the prognosis and immune status in breast cancer.
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研究概要
这个基于 10 个基因的 EMT 特征能够可靠地预测 BC 预后，并为肿瘤免疫微环境提供了有价值的见解。
研究思路结论见上方概要
目的
乳腺癌（BC）发病率持续上升，复发和转移仍是导致死亡的主要原因。上皮-间质转化（EMT）与上皮细胞获得侵袭功能相关，同时也促进对抗癌治疗的耐药性。在此，我们开发了一个基于EMT的预后模型，以增强BC结局预测。
方法
来自 TCGA 的临床和基因表达数据被随机分配到发现队列和验证队列。利用单因素 Cox 回归和 LASSO 分析构建预后特征。应用 Cell-Type Identification by Estimating Relative Subsets of RNA Transcripts 和 ESTIMATE 算法评估肿瘤微环境（TME）。使用 GSEA 发现富集的免疫相关通路。在 MCF-7 和 MDA-MB-231 细胞中敲低和过表达 SDC1，并通过 CCK-8、流式细胞术、Transwell 和 Western blot 评估其对细胞增殖、凋亡、迁移、侵袭和 EMT 关键标志物的影响。
结果
10个EMT相关基因（TP63、TFPI2、ALX4、F2RL2、LEF1、PDLIM4、NDRG2、HMGB3、SDC1和KRT17）与总生存期显示出显著关联。由此得到的特征用于将个体分为高风险组和低风险组，两个队列中两组预后差异显著。高风险患者中M0巨噬细胞、活化NK 细胞、记忆活化CD4+ T细胞及免疫评分均较低。GSEA显示低风险组在免疫相关通路中富集程度更高，包括细胞黏附分子、细胞因子-细胞因子受体相互作用和T细胞受体信号通路。SDC1表达在肿瘤组织中显著升高，并与多项临床和病理特征相关。体外敲低SDC1可抑制BC细胞的增殖、迁移和侵袭，诱导凋亡并逆转EMT过程。过表达SDC1则具有相反的促癌作用。
展开英文摘要原文
OBJECTIVE
Breast cancer (BC) incidence continues to rise, and recurrence and metastasis remain major contributors to mortality. The epithelial-mesenchymal transition (EMT), associated with the acquisition of invasive functions by epithelial cells, also promotes resistance to anticancer therapies. Here, an EMT-based prognostic model was developed to enhance BC outcome prediction.
METHODS
Clinical and gene expression data from the TCGA were randomly assigned to discovery and validation cohorts. Univariate Cox regression and LASSO analyses were utilized to develop a prognostic signature. The Cell-Type Identification by Estimating Relative Subsets of RNA Transcripts and ESTIMATE algorithms were applied to evaluate the tumor microenvironment (TME). Enriched immune-associated pathways were found using GSEA. SDC1 was knocked down and overexpressed in MCF-7 and MDA-MB-231 cells, and its effects on cell proliferation, apoptosis, migration, invasion and EMT key markers were evaluated by CCK-8, flow cytometry, Transwell and Western blot.
RESULTS
Ten EMT-related genes (TP63, TFPI2, ALX4, F2RL2, LEF1, PDLIM4, NDRG2, HMGB3, SDC1, and KRT17) showed significant links with overall survival. The resulting signature was used to allocate individuals into high- and low-risk groups with distinct prognoses in both cohorts. M0 macrophages, activated natural killer cells, memory-activated CD4 + T cells, and immunological scores were all lower in high-risk patients. GSEA revealed that the low-risk group demonstrated greater enrichment in immune-related pathways, including cell adhesion molecules, cytokine-cytokine receptor interactions, and T-cell receptor signaling. SDC1 expression was markedly raised in tumor tissues and correlated with several clinical and pathological features. Knockdown of SDC1 in vitro inhibited the proliferation, migration and invasion of BC cells, induced apoptosis and reversed EMT process. Overexpression of SDC1 had the opposite cancer-promoting effect.
CONCLUSION
This ten-gene EMT-based signature reliably predicts BC prognosis and offers valuable insight into the tumor immune microenvironment.
论文信息
- 作者
- Wu Z、Zheng J、Men S、Sui S、Yan W、Liu Y、Han M
- 单位
- Breast Disease Diagnosis and Treatment Center, The First Hospital of Qinhuangdao Qinhuangdao 066000, Hebei, China.China
- 期刊
- American journal of translational research2026
- 原文标识
- PubMed 42007152 · DOI 10.62347/JQQX7009
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