Single Cell Transcriptome in Colorectal Cancer—Current Updates on Its Application in Metastasis, Chemoresistance and the Roles of Circulating Tumor Cells

Abstract

Colorectal cancer (CRC) is among the most common cancer worldwide, a challenge for research, and a model for studying the molecular mechanisms involved in its development. Previously, bulk transcriptomics analyses were utilized to classify CRC based on its distinct molecular and clinicopathological features for prognosis and diagnosis of patients. The introduction of single-cell transcriptomics completely turned the table by enabling the examination of the expression levels of individual cancer cell within a single tumor. In this review, we highlighted the importance of these single-cell transcriptomics analyses as well as suggesting circulating tumor cells (CTCs) as the main focus of single-cell RNA sequencing. Characterization of these cells might reveal the intratumoral heterogeneity present in CRC while providing critical insights into cancer metastasis. To summarize, we believed the analysis of gene expression patterns of CTC from CRC at single-cell resolution holds the potential to provide key information for identification of prognostic and diagnostic markers as well as the development of precise and personalized cancer treatment.

Genetic Alterations of Metastatic Colorectal Cancer

“…Metastatic CRCs are among the tumors displaying the highest levels of single-nucleotide variants (SNVs), with only urinary tract, esophagus, lung cancers and melanoma exhibiting higher levels among 20 different types of metastatic cancers [ 23 ]. Only 4% of metastatic CRCs displayed an MSI genotype/phenotype, a frequency that is lower than that reported for primary CRC, a finding that can be explained by the lower tendency of these tumors to metastasize [ 13 ]. Copy number alterations are frequent in metastatic CRC; an extreme form of CNA can be caused by whole genome duplication (WGD), an event frequent (>60% of cases) in metastatic CRCs, among the metastatic tumors most frequently showing WGD [ 23 ].…”

“…The complex, variable and potentially confounding role of microenvironment in the evaluation of the transcriptomic expression of CRC, highlights the need of performing analyses at single-cell level as a tool to better define and understand intratumoral heterogeneity [ 13 ]. Only few studies have explored single-cell transcriptomic in CRC samples.…”

“…Very few studies have explored the gene expression profile observed at the level of metastatic CRC lesions. Kamal et al reported the comparative analysis of the transcriptomic profile of primary tumors and corresponding metastases (liver and lung metastases) in some CRC patients [ 13 ]. According to the gene expression profile, two types of distant metastases were identified: M1 and M2 [ 13 ].…”

“…Kamal et al reported the comparative analysis of the transcriptomic profile of primary tumors and corresponding metastases (liver and lung metastases) in some CRC patients [ 13 ]. According to the gene expression profile, two types of distant metastases were identified: M1 and M2 [ 13 ]. The M1 metastatic group is characterized by strong activation of inflammatory and immune response pathways (including immune evasion pathways, such as those involving PD-1/-L1 signaling) and enrichment in EMT activity.…”

Pathologic evolution-related Gene Analysis based on both single-cell and bulk transcriptomics in Colorectal Cancer

“…With the iteration of cell sequencing technology, more details about differentiation map and transcriptional heterogeneity have been clarified 28 , 29 . The application of scRNA-Seq facilitates the excavation of tumorigenesis and molecular classifications compared to bulk sequencing 30 - 32 . By combining scRNA-Seq with clinical characteristics, we revealed the hub genes in the course of CRC pathologic stage evolution and clarified the impact of differential cell infiltration classifications on CRC prognosis based on hub gene expression.…”