Single Cell Omics of Breast Cancer: An Update on Characterization and Diagnosis

Abstract

Breast cancer is recognized for its different clinical behaviors and patient outcomes, regardless of common histopathological features at diagnosis. The heterogeneity and dynamics of breast cancer undergoing clonal evolution produces cells with distinct degrees of drug resistance and metastatic potential. Presently, single cell analysis have made outstanding advancements, overshadowing the hurdles of heterogeneity linked with vast populations. The speedy progression in sequencing analysis now allow unbiased, high-output and high-resolution elucidation of the heterogeneity from individual cell within a population. Classical therapeutics strategies for individual patients are governed by the presence and absence of expression pattern of the estrogen and progesterone receptors and human epidermal growth factor receptor 2. However, such tactics for clinical classification have fruitfulness in selection of targeted therapies, short-term patient responses but unable to predict the long-term survival. In any phenotypic alterations, like breast cancer disease, molecular signature have proven its implication, as we aware that individual cell's state is regulated at diverse levels, such as DNA, RNA and protein, by multifaceted interplay of intrinsic biomolecules pathways existing in the organism and extrinsic stimuli such as ambient environment. Thus for complete understanding, complete profiling of single cell requires a synchronous investigations from different levels (multi-omics) to avoid incomplete information produced from single cell. In this article, initially we briefed on novel updates of various methods available to explore omics and then we finally pinpointed on various omics (i.e. genomics, transcriptomics, epigenomics, proteomics and metabolomics) data and few special aspects of circulating tumor cells, disseminated tumor cells and cancer stem cells, so far available from various studies that can be used for better management of breast cancer patients.

Breast cancer in the era of integrating “Omics” approaches

“…In fact, even a comprehensive understanding of the state of genes, transcripts, and proteins in a living system is not sufficient to reveal its phenotype [ 132 , 133 ]. When combining metabolomics with genomics, possibly transcriptomics, and proteomics, a complete understanding of biological mechanisms from a system-wide perspective can be provided [ 7 ]. It is now well accepted the idea that metabolites represent the link between genotype and phenotype, and that the study of metabolome offers a significant advantage, allowing to highlight the end-point markers of biological events [ 133 ].…”

“…Specifically, it is defined as intratumoral when cells within a tumor in a single patient are involved, while intertumoral when cells of the same subgroup of tumors in different patients are involved [ 2 ]. Thus, the heterogeneity found among BCs led to the concept that BC is not a single disease and rather represents a group of distinct neoplastic diseases of the breast and its cells [ 7 ]. Nowadays, therapeutic options for BC treatment include surgery, radiotherapy, chemotherapy, and targeted therapies [ 4 , 8 ].…”

How Lineage Tracing Studies Can Unveil Tumor Heterogeneity in Breast Cancer

“…Beyond lineage tracing, multi-omic and high-throughput methods will help us to understand the complex genomics that underlie the human cancer disease. Indeed, single-cell genomics has enabled us to associate specific genetic mutations with different molecular subtypes [ 103 ], and single-cell transcriptomics has provided cancer-specific gene signatures that could help clinicians to determine the prognosis of patients [ 104 ]. For instance, there are currently different gene expression profiling tests for breast cancer in clinics, such as MammaPrint ® and Oncotype DX ® , both of which predict the risk of distant disease recurrence.…”

Vulnerability of Triple-Negative Breast Cancer to Saponin Formosanin C-Induced Ferroptosis

“…Luminal A, luminal B, HER2-positive, and TNBC cases account for up to 70%, 10–20%, 5–15%, and ~15% of all breast cancer patients, respectively [ 2 , 3 ]. Compared to luminal A, luminal B has a worse prognosis [ 4 ]. Drug targeting of HER2 is known to substantially improve the prognosis of HER2-positive breast cancer [ 5 ].…”