Appearance
Using single-cell sequencing technology to detect circulating tumor cells in solid tumors.
Literature Information
| DOI | 10.1186/s12943-021-01392-w |
|---|---|
| PMID | 34412644 |
| Journal | Molecular cancer |
| Impact Factor | 33.9 |
| JCR Quartile | Q1 |
| Publication Year | 2021 |
| Times Cited | 55 |
| Keywords | Circulating tumor cells, Research progress, Single-cell sequencing, Tumor heterogeneity |
| Literature Type | Journal Article, Research Support, Non-U.S. Gov't, Review |
| ISSN | 1476-4598 |
| Pages | 104 |
| Issue | 20(1) |
| Authors | Jiasheng Xu, Kaili Liao, Xi Yang, Chengfeng Wu, Wei Wu |
TL;DR
This study explores the potential of single-cell sequencing of circulating tumor cells (CTCs) to overcome tumor heterogeneity and elucidate the genomic characteristics of low-abundance tumor stem cells. By analyzing the differences in single-cell genomes, transcriptomes, and epigenetic profiles among CTCs and tumor tissues, the research provides valuable insights into tumor biology and enhances approaches for tumor typing, metastasis analysis, and treatment strategies.
Search for more papers on MaltSci.com
Circulating tumor cells · Research progress · Single-cell sequencing · Tumor heterogeneity
Abstract
Circulating tumor cells are tumor cells with high vitality and high metastatic potential that invade and shed into the peripheral blood from primary solid tumors or metastatic foci. Due to the heterogeneity of tumors, it is difficult for high-throughput sequencing analysis of tumor tissues to find the genomic characteristics of low-abundance tumor stem cells. Single-cell sequencing of circulating tumor cells avoids interference from tumor heterogeneity by comparing the differences between single-cell genomes, transcriptomes, and epigenetic groups among circulating tumor cells, primary and metastatic tumors, and metastatic lymph nodes in patients' peripheral blood, providing a new perspective for understanding the biological process of tumors. This article describes the identification, biological characteristics, and single-cell genome-wide variation in circulating tumor cells and summarizes the application of single-cell sequencing technology to tumor typing, metastasis analysis, progression detection, and adjuvant therapy.
MaltSci.com AI Research Service
Intelligent ReadingAnswer any question about the paper and explain complex charts and formulas
Locate StatementsFind traces of a specific claim within the paper
Add to KBasePerform data extraction, report drafting, and advanced knowledge mining
Primary Questions Addressed
- What are the potential advantages of using single-cell sequencing over traditional bulk sequencing methods in the study of circulating tumor cells?
- How does the heterogeneity of circulating tumor cells impact their detection and analysis using single-cell sequencing technology?
- In what ways can single-cell sequencing contribute to personalized treatment strategies for patients with solid tumors?
- What specific genomic characteristics of circulating tumor cells have been identified through single-cell sequencing, and how do these inform tumor biology?
- How might advancements in single-cell sequencing technology enhance our understanding of tumor metastasis and progression in clinical settings?
Key Findings
Research Background and Purpose
Circulating tumor cells (CTCs) are cancer cells that have detached from primary or metastatic tumors and entered the bloodstream, exhibiting high metastatic potential. The heterogeneity of tumors complicates the identification of genomic characteristics of low-abundance tumor cells using high-throughput sequencing of mixed tumor samples. This study reviews the application of single-cell sequencing technology to analyze CTCs, providing insights into tumor biology, including tumor typing, metastasis, and treatment responses.
Main Methods/Materials/Experimental Design
The study employs single-cell sequencing technology to analyze CTCs, comparing genomic, transcriptomic, and epigenetic differences among CTCs, primary tumors, and metastatic sites. The following flowchart outlines the methodology:
- Sample Collection: Blood samples from patients with solid tumors are collected.
- CTC Enrichment: Techniques include positive and negative selection based on cell surface markers (e.g., EpCAM) and microfluidic chips.
- Single-Cell Sorting: Methods such as micromanipulation, microfluidics, and DEPArray are used to isolate single CTCs.
- Whole Genome Amplification: Amplification methods like Multiple Displacement Amplification (MDA) are utilized to increase DNA yield for sequencing.
- Single-Cell Sequencing: High-throughput sequencing technologies are employed to analyze genomic data from isolated CTCs.
- Data Analysis: Bioinformatics tools are used to process and interpret the sequencing data, focusing on genomic variations and tumor heterogeneity.
Key Results and Findings
- Single-cell sequencing revealed significant heterogeneity among CTCs, including variations in mutation status (e.g., KRAS, BRAF) and copy number alterations.
- CTCs displayed genomic features consistent with both primary tumors and metastases, suggesting they can provide real-time insights into tumor evolution and resistance mechanisms.
- The study identified that CTCs can serve as valuable biomarkers for monitoring treatment responses and predicting patient prognosis.
Main Conclusions/Significance/Innovativeness
The application of single-cell sequencing to CTCs offers a novel approach to understanding tumor biology and heterogeneity. This technology enables the identification of critical genetic alterations that may inform personalized treatment strategies. It highlights the potential of CTCs as a non-invasive biomarker for real-time monitoring of tumor progression and therapeutic responses.
Research Limitations and Future Directions
- Limitations: The study acknowledges challenges such as low CTC abundance, technical variability in enrichment and sequencing methods, and the complexity of data analysis.
- Future Directions: There is a need for further refinement of single-cell sequencing techniques and the integration of multi-omics approaches to enhance the understanding of tumor heterogeneity and improve clinical outcomes in cancer therapy. The potential for using CTC analysis in early detection and monitoring of minimal residual disease is also highlighted as a promising area for future research.
References
- TP53 mutations detected in circulating tumor cells present in the blood of metastatic triple negative breast cancer patients. - Sandra V Fernandez;Catherine Bingham;Patricia Fittipaldi;Laura Austin;Juan Palazzo;Gary Palmer;Katherine Alpaugh;Massimo Cristofanilli - Breast cancer research : BCR (2014)
- Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer. - Jens G Lohr;Viktor A Adalsteinsson;Kristian Cibulskis;Atish D Choudhury;Mara Rosenberg;Peter Cruz-Gordillo;Joshua M Francis;Cheng-Zhong Zhang;Alex K Shalek;Rahul Satija;John J Trombetta;Diana Lu;Naren Tallapragada;Narmin Tahirova;Sora Kim;Brendan Blumenstiel;Carrie Sougnez;Alarice Lowe;Bang Wong;Daniel Auclair;Eliezer M Van Allen;Mari Nakabayashi;Rosina T Lis;Gwo-Shu M Lee;Tiantian Li;Matthew S Chabot;Amy Ly;Mary-Ellen Taplin;Thomas E Clancy;Massimo Loda;Aviv Regev;Matthew Meyerson;William C Hahn;Philip W Kantoff;Todd R Golub;Gad Getz;Jesse S Boehm;J Christopher Love - Nature biotechnology (2014)
- Reproducible copy number variation patterns among single circulating tumor cells of lung cancer patients. - Xiaohui Ni;Minglei Zhuo;Zhe Su;Jianchun Duan;Yan Gao;Zhijie Wang;Chenghang Zong;Hua Bai;Alec R Chapman;Jun Zhao;Liya Xu;Tongtong An;Qi Ma;Yuyan Wang;Meina Wu;Yu Sun;Shuhang Wang;Zhenxiang Li;Xiaodan Yang;Jun Yong;Xiao-Dong Su;Youyong Lu;Fan Bai;X Sunney Xie;Jie Wang - Proceedings of the National Academy of Sciences of the United States of America (2013)
- Cell-Autonomous versus Systemic Akt Isoform Deletions Uncovered New Roles for Akt1 and Akt2 in Breast Cancer. - Xinyu Chen;Majd M Ariss;Gopalakrishnan Ramakrishnan;Veronique Nogueira;Catherine Blaha;William Putzbach;Abul B M M K Islam;Maxim V Frolov;Nissim Hay - Molecular cell (2020)
- Single-Cell Multiomics Sequencing Reveals Prevalent Genomic Alterations in Tumor Stromal Cells of Human Colorectal Cancer. - Yuan Zhou;Shuhui Bian;Xin Zhou;Yueli Cui;Wendong Wang;Lu Wen;Limei Guo;Wei Fu;Fuchou Tang - Cancer cell (2020)
- Robust gene expression programs underlie recurrent cell states and phenotype switching in melanoma. - Jasper Wouters;Zeynep Kalender-Atak;Liesbeth Minnoye;Katina I Spanier;Maxime De Waegeneer;Carmen Bravo González-Blas;David Mauduit;Kristofer Davie;Gert Hulselmans;Ahmad Najem;Michael Dewaele;Dennis Pedri;Florian Rambow;Samira Makhzami;Valerie Christiaens;Frederik Ceyssens;Ghanem Ghanem;Jean-Christophe Marine;Suresh Poovathingal;Stein Aerts - Nature cell biology (2020)
- Therapy-Induced Evolution of Human Lung Cancer Revealed by Single-Cell RNA Sequencing. - Ashley Maynard;Caroline E McCoach;Julia K Rotow;Lincoln Harris;Franziska Haderk;D Lucas Kerr;Elizabeth A Yu;Erin L Schenk;Weilun Tan;Alexander Zee;Michelle Tan;Philippe Gui;Tasha Lea;Wei Wu;Anatoly Urisman;Kirk Jones;Rene Sit;Pallav K Kolli;Eric Seeley;Yaron Gesthalter;Daniel D Le;Kevin A Yamauchi;David M Naeger;Sourav Bandyopadhyay;Khyati Shah;Lauren Cech;Nicholas J Thomas;Anshal Gupta;Mayra Gonzalez;Hien Do;Lisa Tan;Bianca Bacaltos;Rafael Gomez-Sjoberg;Matthew Gubens;Thierry Jahan;Johannes R Kratz;David Jablons;Norma Neff;Robert C Doebele;Jonathan Weissman;Collin M Blakely;Spyros Darmanis;Trever G Bivona - Cell (2020)
- Single-cell analysis reveals transcriptomic remodellings in distinct cell types that contribute to human prostate cancer progression. - Sujun Chen;Guanghui Zhu;Yue Yang;Fubo Wang;Yu-Tian Xiao;Na Zhang;Xiaojie Bian;Yasheng Zhu;Yongwei Yu;Fei Liu;Keqin Dong;Javier Mariscal;Yin Liu;Fraser Soares;Helen Loo Yau;Bo Zhang;Weidong Chen;Chao Wang;Dai Chen;Qinghua Guo;Zhengfang Yi;Mingyao Liu;Michael Fraser;Daniel D De Carvalho;Paul C Boutros;Dolores Di Vizio;Zhou Jiang;Theodorus van der Kwast;Alejandro Berlin;Song Wu;Jianhua Wang;Housheng Hansen He;Shancheng Ren - Nature cell biology (2021)
- Intratumoral heterogeneity as a therapy resistance mechanism: role of melanoma subpopulations. - Rajasekharan Somasundaram;Jessie Villanueva;Meenhard Herlyn - Advances in pharmacology (San Diego, Calif.) (2012)
- Cancer invasion and the microenvironment: plasticity and reciprocity. - Peter Friedl;Stephanie Alexander - Cell (2011)
Literatures Citing This Work
- Circulating tumor cells: biology and clinical significance. - Danfeng Lin;Lesang Shen;Meng Luo;Kun Zhang;Jinfan Li;Qi Yang;Fangfang Zhu;Dan Zhou;Shu Zheng;Yiding Chen;Jiaojiao Zhou - Signal transduction and targeted therapy (2021)
- Single-Cell RNA Sequencing Reveals Multiple Pathways and the Tumor Microenvironment Could Lead to Chemotherapy Resistance in Cervical Cancer. - Meijia Gu;Ti He;Yuncong Yuan;Suling Duan;Xin Li;Chao Shen - Frontiers in oncology (2021)
- Single-Cell RNA-Seq Reveals the Promoting Role of Ferroptosis Tendency During Lung Adenocarcinoma EMT Progression. - Jiaxi Yao;Yuchong Zhang;Mengling Li;Zuyu Sun;Tao Liu;Mingfang Zhao;Zhi Li - Frontiers in cell and developmental biology (2021)
- Recent advances and application of whole genome amplification in molecular diagnosis and medicine. - Xiaoyu Wang;Yapeng Liu;Hongna Liu;Wenjing Pan;Jie Ren;Xiangming Zheng;Yimin Tan;Zhu Chen;Yan Deng;Nongyue He;Hui Chen;Song Li - MedComm (2022)
- Correction to: Using single-cell sequencing technology to detect circulating tumor cells in solid tumors. - Jiasheng Xu;Kaili Liao;Xi Yang;Chengfeng Wu;Wei Wu - Molecular cancer (2022)
- Recent advances in targeted drug delivery systems for resistant colorectal cancer. - Masoumeh Sharifi-Azad;Marziyeh Fathi;William C Cho;Abolfazl Barzegari;Hamed Dadashi;Mehdi Dadashpour;Rana Jahanban-Esfahlan - Cancer cell international (2022)
- Clonal barcoding with qPCR detection enables live cell functional analyses for cancer research. - Qiuchen Guo;Milos Spasic;Adam G Maynard;Gregory J Goreczny;Amanuel Bizuayehu;Jessica F Olive;Peter van Galen;Sandra S McAllister - Nature communications (2022)
- A narrative review of circulating tumor cells clusters: A key morphology of cancer cells in circulation promote hematogenous metastasis. - Qiong Chen;Jueyao Zou;Yong He;Yanhong Pan;Gejun Yang;Han Zhao;Ying Huang;Yang Zhao;Aiyun Wang;Wenxing Chen;Yin Lu - Frontiers in oncology (2022)
- ZEB1-activated Notch1 promotes circulating tumor cell migration and invasion in lung squamous cell carcinoma. - Yong Gao;Xinyuan Cheng;Mingfeng Han - Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico (2023)
- Spatial RNA sequencing methods show high resolution of single cell in cancer metastasis and the formation of tumor microenvironment. - Yue Zheng;Xiaofeng Yang - Bioscience reports (2023)
... (45 more literatures)
© 2025 MaltSci - We reshape scientific research with AI technology
