Abstract:

Using single-cell RNA-seq and bulk RNA-seq data， we investigated the expression characteristics and clinical relevance of periostin（POSTN） in estrogen receptor-positive （ER⁺） breast cancer and offered theoretical recommendations for the diagnosis， prognosis， and tailored treatment of ER⁺ breast cancer patients. scRNA-seq data in the gene expression omnibus （GEO） database were used to identify the cell subsets of ER⁺ breast cancer and the expression characteristics of POSTN. POSTN and cancer-associated fibroblasts （CAFs） subtypes with specifically high expression of POSTN were further analyzed by cell trajectory analysis and cell communication. Using the ER⁺ breast cancer data from TCGA-RBCA， the expression level， diagnostic and prognostic value， pathway enrichment， immunotherapy response， and drug sensitivity of POSTN were analyzed. We identified a subgroup of CAFs that strongly express POSTN， named POSTN⁺ CAFs， based on ER⁺ breast cancer scRNA-seq data. They were all in advanced stages of differentiation and were essential for intercellular communication. We found that POSTN is substantially expressed in patients with ER⁺ breast cancer and has diagnostic and prognostic relevance based on the bulk RNA-seq data of ER⁺ breast cancer. According to the functional enrichment analysis， POSTN may play a role in angiogenesis， metastasis and the onset and progression of cancer. Individuals who express lower levels of POSTN may benefit from immunotherapy. Based on scRNA-seq and bulk RNA-seq， this study offers a thorough examination of the biological roles of POSTN and POSTN⁺ CAFs in ER⁺ breast cancer and concluded that POSTN may be a useful biomarker for ER⁺ breast cancer diagnosis， prognosis， treatment response and therapeutic target.

Key words: POSTN, breast cancer, single-cell RNA sequencing, immunecheckpoint, chemotherapy drug sensitivity

摘要：

利用单细胞RNA测序（single-cell RNA-seq，scRNA-seq）和批量RNA测序（bulk RNA-seq）数据，探讨骨膜蛋白（periostin, POSTN）在雌激素受体阳性（estrogen receptor positive，ER⁺）乳腺癌中的表达特征及其临床相关性，为ER⁺乳腺癌患者的诊断、预后和个体化治疗提供理论建议。利用基因表达总库（gene expression omnibus，GEO）中的scRNA-seq数据鉴定ER⁺乳腺癌的细胞亚群和POSTN的表达特征。通过细胞轨迹和细胞通讯进一步分析POSTN和特异性高表达POSTN的癌症相关成纤维细胞（cancer-associated fibroblasts，CAFs）亚型。利用癌症基因组图谱（the cancer genome atlas，TCGA）数据库中的ER⁺乳腺癌数据，分析POSTN的表达水平、诊断和预后价值、通路富集、免疫治疗反应和药物敏感性。基于ER⁺乳腺癌的scRNA-seq数据，鉴定出一组高表达POSTN的CAFs，命名为POSTN⁺ CAFs。它们都处于分化的晚期阶段并对细胞间通讯至关重要；基于ER⁺乳腺癌bulk RNA-seq数据，发现POSTN在ER⁺乳腺癌中显著表达，并且与诊断和预后有相关性；根据功能富集分析，POSTN可能在血管生成、转移以及癌症的发生和进展中发挥作用；POSTN表达水平较低的个体可能从免疫治疗中获益；化疗药物对POSTN低表达的患者影响更大。基于scRNA-seq和bulk RNA-seq，全面分析了POSTN和POSTN⁺ CAFs在ER⁺乳腺癌中的生物学作用，并得出结论，POSTN可能是ER⁺乳腺癌诊断、预后、治疗反应和治疗靶点的生物标志物。

关键词: 骨膜蛋白, 乳腺癌, 单细胞测序, 免疫检查点, 药物敏感性