Tumour Heterogeneity: The Key Advantages of Single-Cell Analysis

Abstract

Tumour heterogeneity refers to the fact that different tumour cells can show distinct morphological and phenotypic profiles, including cellular morphology, gene expression, metabolism, motility, proliferation and metastatic potential. This phenomenon occurs both between tumours (inter-tumour heterogeneity) and within tumours (intra-tumour heterogeneity), and it is caused by genetic and non-genetic factors. The heterogeneity of cancer cells introduces significant challenges in using molecular prognostic markers as well as for classifying patients that might benefit from specific therapies. Thus, research efforts for characterizing heterogeneity would be useful for a better understanding of the causes and progression of disease. It has been suggested that the study of heterogeneity within Circulating Tumour Cells (CTCs) could also reflect the full spectrum of mutations of the disease more accurately than a single biopsy of a primary or metastatic tumour. In previous years, many high throughput methodologies have raised for the study of heterogeneity at different levels (i.e., RNA, DNA, protein and epigenetic events). The aim of the current review is to stress clinical implications of tumour heterogeneity, as well as current available methodologies for their study, paying specific attention to those able to assess heterogeneity at the single cell level.

Tumour-on-a-chip: microfluidic models of tumour morphology, growth and microenvironment

“…The PDMS/glass microfluidic chip with the flow focusing design produced droplets containing single cancer cells and allowed real-time monitoring of lactate release within each individual droplet [203]. Performing metabolic analysis on single populations of tumour cells can yield significant insights into the mechanisms of tumour heterogeneity and energy metabolism reprogramming, both are important for predicting cancer metastatic potential as well as drug resistance [204].…”

Mechanisms and clinical implications of tumor heterogeneity and convergence on recurrent phenotypes

“…Not only have differences at these -omic levels been detected as a cancer progresses through time (temporal heterogeneity), but differences have also been detected across space (spatial heterogeneity) [9–11]. Spatial heterogeneity can be both intratumoral, i.e., within a single primary or metastatic tumor, and intrapatient, i.e, between different tumors within the same person [12, 13]. Thus, as a patient’s cancer progresses, subclones, defined as genetically distinct groups of tumor cells descending from a common ancestor, can be identified, and their evolutionary trajectory can be followed as each subclone responds to or resists treatment.…”

The advancements of genomics and data integration in sarcoma research

“…Furthermore, they can assist in early detection of rare tumor cells and monitoring circulating tumor cells. Single-cell DNA and RNA sequencing are two important and widely used tools for single-cell analysis [82,83] . From distinguishing colorectal…”