Omics-Based Investigations of Breast Cancer

Abstract

Breast cancer (BC) is characterized by an extensive genotypic and phenotypic heterogeneity. In-depth investigations into the molecular bases of BC phenotypes, carcinogenesis, progression, and metastasis are necessary for accurate diagnoses, prognoses, and therapy assessments in predictive, precision, and personalized oncology. This review discusses both classic as well as several novel omics fields that are involved or should be used in modern BC investigations, which may be integrated as a holistic term, onco-breastomics. Rapid and recent advances in molecular profiling strategies and analytical techniques based on high-throughput sequencing and mass spectrometry (MS) development have generated large-scale multi-omics datasets, mainly emerging from the three ”big omics”, based on the central dogma of molecular biology: genomics, transcriptomics, and proteomics. Metabolomics-based approaches also reflect the dynamic response of BC cells to genetic modifications. Interactomics promotes a holistic view in BC research by constructing and characterizing protein–protein interaction (PPI) networks that provide a novel hypothesis for the pathophysiological processes involved in BC progression and subtyping. The emergence of new omics- and epiomics-based multidimensional approaches provide opportunities to gain insights into BC heterogeneity and its underlying mechanisms. The three main epiomics fields (epigenomics, epitranscriptomics, and epiproteomics) are focused on the epigenetic DNA changes, RNAs modifications, and posttranslational modifications (PTMs) affecting protein functions for an in-depth understanding of cancer cell proliferation, migration, and invasion. Novel omics fields, such as epichaperomics or epimetabolomics, could investigate the modifications in the interactome induced by stressors and provide PPI changes, as well as in metabolites, as drivers of BC-causing phenotypes. Over the last years, several proteomics-derived omics, such as matrisomics, exosomics, secretomics, kinomics, phosphoproteomics, or immunomics, provided valuable data for a deep understanding of dysregulated pathways in BC cells and their tumor microenvironment (TME) or tumor immune microenvironment (TIMW). Most of these omics datasets are still assessed individually using distinct approches and do not generate the desired and expected global-integrative knowledge with applications in clinical diagnostics. However, several hyphenated omics approaches, such as proteo-genomics, proteo-transcriptomics, and phosphoproteomics-exosomics are useful for the identification of putative BC biomarkers and therapeutic targets. To develop non-invasive diagnostic tests and to discover new biomarkers for BC, classic and novel omics-based strategies allow for significant advances in blood/plasma-based omics. Salivaomics, urinomics, and milkomics appear as integrative omics that may develop a high potential for early and non-invasive diagnoses in BC. Thus, the analysis of the tumor circulome is considered a novel frontier in liquid biopsy. Omics-based investigations have applications in BC modeling, as well as accurate BC classification and subtype characterization. The future in omics-based investigations of BC may be also focused on multi-omics single-cell analyses.

A retrospective case-control study for Clinical Validation of mutated ZNF208 as a novel biomarker of fatal blast crisis in Chronic Myeloid Leukemia

“…Moreover, incorporation of next-generation sequencing, and other high-throughput techniques have refined the discovery and validation of diagnostic and prognostic biomarkers and their incorporation into precision medicine [43][44][45][46][47][48][49][50][51].…”

Proteogenomics in Cancer: Then and Now

“…In fact, some of the clearly defined omics we mentioned above were involved in very limited research papers, meaning they are poorly investigated. Furthermore, during our reviewing process, some -omic terms could not be matched to an exact definition in dictionaries or research papers, but were included in a statement in a previous review . They are matrisomics, angiomics, epichaperomics, metadegradomics, adhesomics, and stressomics.…”

“…Finally, metabolomics is the study of all the metabolites present in cells, tissues, and organs . Along with time, many new approaches are contributing to expand -omics subfields. , The definitions or research contents of -omics topics in biology are summarized briefly in Table (in alphabetical order).…”

Recent Contributions of Mass Spectrometry-Based “Omics” in the Studies of Breast Cancer

“…Suspicious mammogram findings could be categorized for cancer by glycan biomarkers expressed in tissues . Numerous proteins were identified in different studies which had links with progression, and disease subtypes are reviewed by Neagu (2023) . You (2022) in their review proposed androgen receptor (AR) status determination as a diagnostic criterion in BC.…”

“…32 Numerous proteins were identified in different studies which had links with progression, and disease subtypes are reviewed by Neagu (2023). 141 You (2022) in their review proposed androgen receptor (AR) status determination as a diagnostic criterion in BC. They reviewed AR acting as a biomarker and prognostic evaluator in different subtypes of breast cancers.…”