Protein co-expression networks identified from HOT lesions of ER+HER2–Ki-67high luminal breast carcinomas

Abstract

Patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative/Ki-67-high (ER+HER2–Ki-67high) luminal breast cancer have a worse prognosis and do not respond to hormonal treatment and chemotherapy. This study sought to identify disease-related protein networks significantly associated with this subtype, by assessing in-depth proteomes of 10 lesions of high and low Ki-67 values (HOT, five; COLD, five) microdissected from the five tumors. Weighted correlation network analysis screened by over-representative analysis identified the five modules significantly associated with the HOT lesions. Pathway enrichment analysis, together with causal network analysis, revealed pathways of ribosome-associated quality controls, heat shock response by oxidative stress and hypoxia, angiogenesis, and oxidative phosphorylation. A semi-quantitative correlation of key-protein expressions, protein co-regulation analysis, and multivariate correlation analysis suggested co-regulations via network-network interaction among the four HOT-characteristic modules. Predicted highly activated master and upstream regulators were most characteristic to ER-positive breast cancer and associated with oncogenic transformation, as well as resistance to chemotherapy and endocrine therapy. Interestingly, inhibited intervention causal networks of numerous chemical inhibitors were predicted within the top 10 lists for the WM2 and WM5 modules, suggesting involvement of potential therapeutic targets in those data-driven networks. Our findings may help develop therapeutic strategies to benefit patients.

The Breast Cancer Protein Co-Expression Landscape

“…In this context, and in connection with breast cancer, we should remark about the recent contribution by Yamada and coworkers [ 40 ]. The authors performed a detailed analysis of protein co-expression networks on a rigorously selected set of 10 lesions in five estrogen-receptor-positive/HER2-negative/Ki-67-positive luminal breast tumors.…”

Disease-related protein co-expression networks are associated with the prognosis of resectable node-positive pancreatic ductal adenocarcinoma

“…The present study aimed at identifying the protein co-expression networks that are significantly associated with a poor and better clinical outcome in patients with resectable, node-positive (UICC stage IIB/JPS stage III) PDAC. Weighted gene co-expression network analysis (WGCNA) 9 , 10 was applied to quantitative proteome datasets of PDAC. Our case selection strategy and the workflow of the employed network-based discovery bioinformatics analysis (taking place after the MS-based proteomic analysis) are presented in Fig.…”