Department of Clinical Sciences Lund, Oncology, Lund University and Skåne University Hospital, Lund, Sweden.
Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Sweden.
PLoS One. 2024 Jul 3;19(7):e0305222. doi: 10.1371/journal.pone.0305222. eCollection 2024.
Currently, there are few treatment-predictive and prognostic biomarkers in triple-negative breast cancer (TNBC). Caveolin-1 (CAV1) is linked to chemoresistance and several important processes involved in tumor progression and metastasis, such as epithelial-mesenchymal transition (EMT). Herein, we report that high CAV1 gene expression is an independent factor of poor prognosis in TNBC.
CAV1 gene expression was compared across different molecular features (e.g., PAM50 subtypes). CAV1 expression was assessed in relation to clinical outcomes using Cox regression adjusted for clinicopathological predictors. Differential gene expression and gene set enrichment analyses were applied to compare high- and low-expressing CAV1 tumors. Tumor microenvironment composition of high- and low-expressing CAV1 tumors was estimated using ECOTYPER. Tumor tissue microarrays were used to evaluate CAV1 protein levels in stromal and malignant cells.
In the SCAN-B (n = 525) and GSE31519 (n = 327) cohorts, patients with CAV1-high tumors had an increased incidence of early recurrence adjusted HR 1.78 (95% CI 1.12-2.81) and 2.20 (95% CI 1.39-3.47), respectively. In further analysis, high CAV1 gene expression was associated with a molecular profile indicating altered metabolism, neovascularization, chemoresistance, EMT, suppressed immune response, and active tumor microenvironment. Protein levels of CAV1 in malignant and stromal cells were not correlated with CAV1 gene expression.
CAV1 gene expression in TNBC is a biomarker that merits further investigation in clinical trials and as a therapeutic target.
目前，三阴性乳腺癌（TNBC）缺乏治疗预测和预后的生物标志物。窖蛋白-1（CAV1）与化疗耐药以及肿瘤进展和转移涉及的几个重要过程有关，如上皮间质转化（EMT）。在此，我们报告 CAV1 基因高表达是 TNBC 预后不良的独立因素。
比较不同分子特征（例如，PAM50 亚型）之间的 CAV1 基因表达。使用 Cox 回归调整临床病理预测因子，评估 CAV1 表达与临床结局的关系。应用差异基因表达和基因集富集分析比较高表达和低表达 CAV1 肿瘤。使用 ECOTYPER 估计高表达和低表达 CAV1 肿瘤的肿瘤微环境组成。使用肿瘤组织微阵列评估 CAV1 蛋白在基质和恶性细胞中的水平。
在 SCAN-B（n=525）和 GSE31519（n=327）队列中，CAV1 高肿瘤患者的早期复发发生率增加，调整后的 HR 分别为 1.78（95%CI 1.12-2.81）和 2.20（95%CI 1.39-3.47）。进一步分析显示，高 CAV1 基因表达与提示代谢改变、新生血管生成、化疗耐药、EMT、抑制免疫反应和活跃的肿瘤微环境的分子特征相关。恶性和基质细胞中 CAV1 蛋白水平与 CAV1 基因表达无相关性。
TNBC 中的 CAV1 基因表达是一个值得在临床试验和作为治疗靶点进一步研究的生物标志物。
