Proteogenomic Workflow Reveals Molecular Phenotypes Related to Breast Cancer Mammographic Appearance

Proteogenomic approaches have enabled the generat̲ion of
novel information levels when compared to single omics studies although
burdened by extensive experimental efforts. Here, we improved a data-independent
acquisition mass spectrometry proteogenomic workflow to reveal distinct
molecular features related to mammographic appearances in breast cancer.
Our results reveal splicing processes detectable at the protein level
and highlight quantitation and pathway complementarity between RNA
and protein data. Furthermore, we confirm previously detected enrichments
of molecular pathways associated with estrogen receptor-dependent
activity and provide novel evidence of epithelial-to-mesenchymal activity
in mammography-detected spiculated tumors. Several transcript–protein
pairs displayed radically different abundances depending on the overall
clinical properties of the tumor. These results demonstrate that there
are differentially regulated protein networks in clinically relevant
tumor subgroups, which in turn alter both cancer biology and the abundance
of biomarker candidates and drug targets.

蛋白质组学与基因组学相结合的方法相较于单一组学的研究，虽需付出大量实验努力，却开启了新的信息层次。本研究中，我们对一种独立于数据获取的质谱蛋白质组学工作流程进行了改进，旨在揭示与乳腺癌症乳腺影像学特征相关的独特分子特征。我们的研究结果表明，在蛋白质水平上可检测到剪接过程，并强调了RNA与蛋白质数据在定量和通路互补性方面的显著关联。此外，我们证实了先前检测到的与雌激素受体依赖性活动相关的分子途径的富集，并为乳腺影像学检测到的刺状肿瘤中上皮间质转化活动提供了新的证据。某些转录-蛋白质对在肿瘤的临床整体特性影响下显示出截然不同的丰度。这些结果揭示了在临床相关的肿瘤亚组中存在差异调节的蛋白质网络，进而改变癌症生物学以及生物标志物候选者和药物靶点的丰度。