Department of Clinical Sciences Lund, Oncology, Lund University and Skåne University Hospital, Barngatan 4, 221 85, Lund, Sweden.
Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Skåne, Sweden.
Sci Rep. 2024 Mar 20;14(1):6675. doi: 10.1038/s41598-024-57365-8.
Combining information from the tumor microenvironment (TME) with PAM50 Risk of Recurrence (ROR) score could improve breast cancer prognostication. Caveolin-1 (CAV1) is a marker of an active TME. CAV1 is a membrane protein involved in cell signaling, extracellular matrix organization, and tumor-stroma interactions. We sought to investigate CAV1 gene expression in relation to PAM50 subtypes, ROR score, and their joint prognostic impact. CAV1 expression was compared between PAM50 subtypes and ROR categories in two cohorts (SCAN-B, n = 5326 and METABRIC, n = 1980). CAV1 expression was assessed in relation to clinical outcomes using Cox regression and adjusted for clinicopathological predictors. Effect modifications between CAV1 expression and ROR categories on clinical outcome were investigated using multiplicative and additive two-way interaction analyses. Differential gene expression and gene set enrichment analyses were applied to compare high and low expressing CAV1 tumors. All samples expressed CAV1 with the highest expression in the Normal-like subtype. Gene modules consistent with epithelial-mesenchymal transition (EMT), hypoxia, and stromal activation were associated with high CAV1 expression. CAV1 expression was inversely associated with ROR category. Interactions between CAV1 expression and ROR categories were observed in both cohorts. High expressing CAV1 tumors conferred worse prognosis only within the group classified as ROR high. ROR gave markedly different prognostic information depending on the underlying CAV1 expression. CAV1, a potential mediator between the malignant cells and TME, could be a useful biomarker that enhances and further refines PAM50 ROR risk stratification in patients with ROR high tumors and a potential therapeutic target.
联合肿瘤微环境（TME）信息与 PAM50 复发风险（ROR）评分可改善乳腺癌预后。窖蛋白-1（CAV1）是活跃的 TME 的标志物。CAV1 是一种参与细胞信号转导、细胞外基质组织和肿瘤-基质相互作用的膜蛋白。我们试图研究 CAV1 基因表达与 PAM50 亚型、ROR 评分及其联合预后影响的关系。在两个队列（SCAN-B，n=5326 和 METABRIC，n=1980）中比较了 CAV1 表达与 PAM50 亚型和 ROR 类别的关系。使用 Cox 回归评估 CAV1 表达与临床结局的关系，并根据临床病理预测因素进行调整。使用乘法和加法双向交互作用分析研究 CAV1 表达与 ROR 类别之间的临床结果的效应修饰。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。所有样本均表达 CAV1，在正常样亚型中表达最高。与上皮-间充质转化（EMT）、缺氧和基质激活一致的基因模块与高 CAV1 表达相关。CAV1 表达与 ROR 类别呈负相关。在两个队列中均观察到 CAV1 表达与 ROR 类别之间的相互作用。高表达 CAV1 肿瘤仅在分类为 ROR 高的组中预后较差。ROR 根据潜在的 CAV1 表达给出了明显不同的预后信息。CAV1 是恶性细胞与 TME 之间的潜在介质，可能是一种有用的生物标志物，可增强并进一步细化 ROR 高肿瘤的 PAM50 ROR 风险分层，并可能成为潜在的治疗靶点。
