Ku Wei-Chi, Phan Nam Nhut, Liu Chih-Yi, Huang Chi-Jung, Liao Chen-Chung, Huang Yen-Chun, Kong Po-Hsin, Tseng Ling-Ming, Huang Chi-Cheng
School of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei, 242, Taiwan.
Greehey's Children Cancer Research Institute, University of Texas Health at San Antonio, San Antonio, TX, USA, 78229.
Biochem Biophys Rep. 2025 Aug 31;44:102210. doi: 10.1016/j.bbrep.2025.102210. eCollection 2025 Dec.
This study aimed to conduct functional proteomics across breast cancer subtypes with bioinformatics analyses.
Candidate proteins were identified using nanoscale liquid chromatography with tandem mass spectrometry (NanoLC-MS/MS) from core needle biopsy samples of early stage (0-III) breast cancers, followed by external validation with public domain gene-expression datasets (TCGA TARGET GTEx and TCGA BRCA).
Seventeen proteins demonstrated significantly differential expression and protein-protein interaction (PPI) found the strong networks including COL2A1, COL11A1, COL6A1, COL6A2, THBS1 and LUM. Public domain databases also showed that , , , and were higher in primary/metastatic tumor than in normal tissue (one-way ANOVA, all P-values less than 0.001), and all six genes were differentially expressed across four molecular subtypes based on hormone receptor (HR) status and human epidermal growth factor receptor II (HER2) status (one-way ANOVA, all P-values less than 0.001). Disease-specific survival discrepancy was observed comparing breast cancer patients of the upper and lower quartile of the collagen family (, , , ), and gene expression signature (log-rank test, P = 0.06).
Functional proteomics suggested that collagen proteins, thrombospondin 1 and lumican are differentially expressed across breast cancer subtypes.
本研究旨在通过生物信息学分析对乳腺癌亚型进行功能蛋白质组学研究。
使用纳升级液相色谱-串联质谱法(NanoLC-MS/MS)从早期(0-III期)乳腺癌的粗针活检样本中鉴定候选蛋白质,随后利用公共领域基因表达数据集(TCGA TARGET GTEx和TCGA BRCA)进行外部验证。
17种蛋白质表现出显著差异表达,蛋白质-蛋白质相互作用(PPI)分析发现了包括COL2A1、COL11A1、COL6A1、COL6A2、THBS1和LUM在内的强大网络。公共领域数据库还显示,COL2A1、COL11A1、COL6A1、COL6A2和THBS1在原发性/转移性肿瘤中的表达高于正常组织(单因素方差分析,所有P值均小于0.001),并且基于激素受体(HR)状态和人表皮生长因子受体II(HER2)状态,这六个基因在四种分子亚型中均存在差异表达(单因素方差分析,所有P值均小于0.001)。比较胶原蛋白家族(COL2A1、COL11A1、COL6A1、COL6A2)、THBS1和LUM基因表达特征处于上四分位数和下四分位数的乳腺癌患者,观察到疾病特异性生存差异(对数秩检验,P = 0.06)。
功能蛋白质组学表明,胶原蛋白、血小板反应蛋白1和纤连蛋白聚糖在乳腺癌亚型中存在差异表达。