Using single-cell sequencing technology to detect circulating tumor cells in solid tumors

Xu, Jiasheng; Liao, Kaili; Xi, Yang; Wu, Chengfeng; Wu, Wei; Han, Shuwen

doi:10.1186/s12943-021-01392-w

Cited by 52 publications

(45 citation statements)

References 83 publications

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“…Single-cell RNA sequencing (scRNA-seq) techniques have emerged as a powerful tool for analyzing the spectrum of cell populations in tissues. Furthermore, these techniques have been widely used for elucidating the complex subpopulations in tissues of organs such as the lung (14), heart (15), and brain (16), as well as in various cancers including melanoma (17), ovarian (18), and colon (19) cancers (20,21).…”

Section: Introductionmentioning

confidence: 99%

Single-Cell RNA Sequencing Reveals Multiple Pathways and the Tumor Microenvironment Could Lead to Chemotherapy Resistance in Cervical Cancer

He²,

Yuan

et al. 2021

Front. Oncol.

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BackgroundCervical cancer is one of the most common gynecological cancers worldwide. The tumor microenvironment significantly influences the therapeutic response and clinical outcome. However, the complex tumor microenvironment of cervical cancer and the molecular mechanisms underlying chemotherapy resistance are not well studied. This study aimed to comprehensively analyze cells from pretreated and chemoresistant cervical cancer tissues to generate a molecular census of cell populations.MethodsBiopsy tissues collected from patients with cervical squamous cell carcinoma, cervical adenocarcinoma, and chronic cervicitis were subjected to single-cell RNA sequencing using the 10× Genomics platform. Unsupervised clustering analysis of cells was performed to identify the main cell types, and important cell clusters were reclustered into subpopulations. Gene expression profiles and functional enrichment analysis were used to explore gene expression and functional differences between cell subpopulations in cervicitis and cervical cancer samples and between chemoresistant and chemosensitive samples.ResultsA total of 24,371 cells were clustered into nine separate cell types, including immune and non-immune cells. Differentially expressed genes between chemoresistant and chemosensitive patients enriched in the phosphoinositide 3-kinase (PI3K)/AKT pathway were involved in tumor development, progression, and apoptosis, which might lead to chemotherapy resistance.ConclusionsOur study provides a comprehensive overview of the cancer microenvironment landscape and characterizes its gene expression and functional difference in chemotherapy resistance. Consequently, our study deepens the insights into cervical cancer biology through the identification of gene markers for diagnosis, prognosis, and therapy.

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Section: Introductionmentioning

confidence: 99%

Single-Cell RNA Sequencing Reveals Multiple Pathways and the Tumor Microenvironment Could Lead to Chemotherapy Resistance in Cervical Cancer

He²,

Yuan

et al. 2021

Front. Oncol.

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“…Indeed, regions containing ERBB2, EGFR, PLCG1, MYC, CCND1, CCND3, and CCNE1 oncogenes were frequently amplified, while tumor suppressor genes such as CDKN2A, CDKN2B, RAD17, and RAD50 were deleted (Figure 2(a)). Given CNVs were highly heterogeneous in specific cancers, 31,32 they may be the result of a random accumulation of CIN. Therefore, stratifying patients based on the states of chromosomal integrity are significant both biologically and clinically.…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of chromosomal integrity in gastric cancers

et al. 2022

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Background A whole-exome or targeted cancer genes panel by next-generation sequencing has been used widely in assisting individualized treatment decisions. Currently, multiple algorithms are developed to estimate DNA copy numbers based on sequencing data, which makes a comprehensive global glance at chromosomal integrity possible. We aim to classify gastric cancers based on chromosomal integrity to guide personalized therapy. Methods We investigated copy number variations (CNV) across the entire genome of 124 gastric carcinomas via exome or targeted sequencing. Chromosomal integrity was classified as chromosomal stability (CS), chromosomal instability (CIN) and intermediate state (CIN/CS) based on CNV results. Chromosomal integrity was correlated to molecular features and clinical characteristics. Results According the states of chromosomal integrity, gastric carcinomas can be stratified into two cohorts: CS and CIN. Our results showed a significant relationship between CIN status and TP53 mutation, but not RB1, phosphatase and tensin homolog (PTEN), or other reported DNA damage repair genes. The mutation frequency of the TP53 gene had great relevance. Our study initially revealed clinical significance of chromosomal integrity that CIN patients were prone to HER2-positive and mucinous adenocarcinoma, while CS patients were a diffuse subtype and poorly differentiated but had longer overall survival. Conclusions We classified gastric carcinomas into two states of chromosomal integrity with clinical implications. The dichotomy is applicable to clinical transformation. We proposed that classifying gastric cancers based on chromosomal integrity would enable us to achieve personalized therapy for patients and may be beneficial to patient stratification in future clinical trials.

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“…ctDNA can be subjected to next-generation sequencing (NGS) to determine mutation profile which provide useful insight about different pathways and the resistance acquisition [ 41 ]. Likely, genetic and transcriptomics heterogeneity of tumors can be interpreted from single CTC sequencing methods and also these kinds of analysis can determine the efficacy of adjuvant therapy, monitor tumor progression and reveal metastasis mechanism in solid tumors [ 42 ]. Equally, CTC detection has prognostic value in CRC, as for localized disease, CTCs enumeration help to stratify patients to adjuvant therapies by identifying cases at a high risk for metastasis.…”

Section: Drug Resistance Mechanisms In Crcmentioning

confidence: 99%

Recent advances in targeted drug delivery systems for resistant colorectal cancer

et al. 2022

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Colorectal cancer (CRC) is one of the deadliest cancers in the world, the incidences and morality rate are rising and poses an important threat to the public health. It is known that multiple drug resistance (MDR) is one of the major obstacles in CRC treatment. Tumor microenvironment plus genomic instability, tumor derived exosomes (TDE), cancer stem cells (CSCs), circulating tumor cells (CTCs), cell-free DNA (cfDNA), as well as cellular signaling pathways are important issues regarding resistance. Since non-targeted therapy causes toxicity, diverse side effects, and undesired efficacy, targeted therapy with contribution of various carriers has been developed to address the mentioned shortcomings. In this paper the underlying causes of MDR and then various targeting strategies including exosomes, liposomes, hydrogels, cell-based carriers and theranostics which are utilized to overcome therapeutic resistance will be described. We also discuss implication of emerging approaches involving single cell approaches and computer-aided drug delivery with high potential for meeting CRC medical needs.

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Using single-cell sequencing technology to detect circulating tumor cells in solid tumors

Cited by 52 publications

References 83 publications

Single-Cell RNA Sequencing Reveals Multiple Pathways and the Tumor Microenvironment Could Lead to Chemotherapy Resistance in Cervical Cancer

Single-Cell RNA Sequencing Reveals Multiple Pathways and the Tumor Microenvironment Could Lead to Chemotherapy Resistance in Cervical Cancer

Clinical significance of chromosomal integrity in gastric cancers

Recent advances in targeted drug delivery systems for resistant colorectal cancer

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