As a highly heterogeneous disease, breast cancer (BRCA) demonstrates a diverse molecular portrait. The well-established molecular classification (PAM50) relies on gene expression profiling. It insufficiently explains the observed clinical and histopathological diversity of BRCAs. This study aims to demographically and clinically characterize the six BRCA subpopulations (basal, HER2-enriched, and four luminal ones) revealed by their proteomic portraits. GMM-based high variate protein selection combined with PCA/UMAP was used for dimensionality reduction, while the k-means algorithm allowed patient clustering. The statistical analysis (log-rank and Gehan–Wilcoxon tests, hazard ratio HR as the effect size ES) showed significant differences across identified subpopulations in Disease-Specific Survival (p= 0.0160) and Progression-Free Interval (p= 0.0264). Luminal subpopulations vary in prognosis (Disease-Free Interval,p= 0.0277). The A2 subpopulation is of the poorest, comparable to the HER2-enriched subpopulation, prognoses (HR = 1.748, referenced to Luminal B, small ES), while A3 is of the best (HR = 0.250, large ES). Similar to PAM50 subtypes, no substantial dependency on demographic and clinical factors was detected across Luminal subpopulations, as measured by χ2test and Cramér’s V for ES, and ANOVA with appropriate post hocs combined withη2or Cohen’s d-type ES, respectively. Progesterone receptors can serve as the potential A2 biomarker within Luminal patients. Further investigation of molecular differences is required to examine the potential prognostic or clinical applications.
作为一种高度异质性疾病，乳腺癌（BRCA）展现出多样化的分子特征。目前成熟的分子分型（PAM50）依赖于基因表达谱分析，但尚不足以解释观察到的乳腺癌临床和组织病理学多样性。本研究旨在通过蛋白质组学特征揭示的六个乳腺癌亚群（基底型、HER2富集型及四种管腔型），从人口统计学和临床特征角度进行系统表征。采用基于高斯混合模型的高变异蛋白筛选结合主成分分析/均匀流形逼近技术进行降维处理，同时运用k均值算法实现患者聚类。统计分析（时序检验与Gehan-Wilcoxon检验，以风险比HR作为效应量ES）显示，不同亚群在疾病特异性生存期（p=0.0160）和无进展间期（p=0.0264）存在显著差异。管腔型亚群的预后呈现异质性（无病间期，p=0.0277），其中A2亚群预后最差（参照Luminal B亚群，HR=1.748，小效应量），与HER2富集型预后相当；而A3亚群预后最佳（HR=0.250，大效应量）。与PAM50亚型相似，通过χ2检验与克莱姆V值（效应量）、方差分析结合相应事后检验及η2或Cohen's d型效应量的综合评估，发现管腔型亚群间未呈现显著的人口统计学或临床因素依赖性。孕激素受体可作为管腔型患者中A2亚群的潜在生物标志物。未来需深入探究分子层面的差异，以评估其潜在的预后判断或临床应用价值。
肿瘤(癌症)患者之家