Application of "omics" sciences to the prediction of bone metastases from breast cancer: State of the art

Abstract

Breast cancer (BC) is the most frequent malignancy and the first cause of cancer-related death in women. The majority of patients with advanced BC develop skeletal metastases which may ultimately lead to serious complications, termed skeletal-related events, that often dramatically impact on quality of life and survival. Therefore, the identification of biomarkers able to stratify BC patient risk to develop bone metastases (BM) is fundamental to define personalized diagnostic and therapeutic strategies, possibly at the earliest stages of the disease. In this regard, the advent of "omics" sciences boosted the investigation of several putative biomarkers of BC osteotropism, including deregulated genes, proteins and microRNAs. The present review revisits the current knowledge on BM development in BC and the most recent studies exploring potential BM-predicting biomarkers, based on the application of omics sciences to the study of primary breast malignancies.

Keywords: ADAMTS1, a disintegrin-like and metalloproteinase with thrombospondin type 1; ALP, alkaline phosphatase; BALP (BSAP), bone-specific alkaline phosphatase; BC, breast cancer; BM, bone metastases; BOLCs, breast osteoblast-like cells; BTM, bone turnover markers; Biomarkers; Bone metastases; Breast cancer; CAPG, capping-protein; CCN3, cellular communication network factor 3; CDH11, cadherin-11; CNV, copy number variation; CTGF, connective tissue-derived growth factor; CTSK, cathepsin K; CTX, C-telopeptide; CXCL, C-X-C-ligand; CXCR, C–X–C motif chemokine receptor; DEGs, differentially expressed genes; DOCK4, dedicator of cytokinesis protein 4; DPD, deoxypyridoline; DTC, disseminated tumour cells; EMT, epithelial-to-mesenchymal transition; ER, estrogen receptor; ERRα, estrogen-related receptor alpha; FAK, focal adhesion kinase; FGF, fibroblast growth factor; FST, follistatin; GIPC1, PDZ domain-containing protein member 1; HR, hazard ratio; Her, human epidermal growth factor; ICAM-1, intercellular adhesion molecule 1; IGF, insulin-like growth factor; IHC, immunohistochemistry; IL, interleukin; LC/MS/MS, liquid chromatography/mass spectrometry/mass spectrometry; MAF, v-maf avian muscolo aponeurotic fibro-sarcoma oncogene homolog; MDA-MB, MD Anderson metastatic BC; MMP1, matrix metalloproteinase-1; NTX, N-telopeptide; OPG, osteoprotegerin; Omics sciences; Osteotropism; P1CP, pro-collagen type I C-terminal; P1NP, pro-collagen type I N-terminal; PDGF, platelet-derived growth factor; PRG1, proteoglycan-1; PTH-rP, parathyroid hormone-related protein; PYD, pyridoline; PgR, progesterone receptor; PlGF, placental growth factor; RANK, receptor activator of nuclear factor к-B; RT-PCR, real time-PCR; SILAC-MS, stable isotope labelling by amino acids in cell culture-mass spectrometry; SNPs, single nucleotide polymorphisms; SPP1, osteopontin; SREs, skeletal-related events; TCGA, the cancer genome atlas; TGF-β, transforming growth factor beta; TNF-α, tumor necrosis factor-α; TRACP-5b, tartrate resistant acid phosphatase-5b; VEGF, vascular endothelial growth factor; ZNF217, zinc-finger protein 217; miRNAs, microRNAs; ncRNAs, noncoding RNA.