Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2022

Open Access 01-12-2022 | Metastasis | Review

Single-cell sequencing: a promising approach for uncovering the mechanisms of tumor metastasis

Authors: Yingying Han, Dan Wang, Lushan Peng, Tao Huang, Xiaoyun He, Junpu Wang, Chunlin Ou

Published in: Journal of Hematology & Oncology | Issue 1/2022

Login to get access

Abstract

Single-cell sequencing (SCS) is an emerging high-throughput technology that can be used to study the genomics, transcriptomics, and epigenetics at a single cell level. SCS is widely used in the diagnosis and treatment of various diseases, including cancer. Over the years, SCS has gradually become an effective clinical tool for the exploration of tumor metastasis mechanisms and the development of treatment strategies. Currently, SCS can be used not only to analyze metastasis-related malignant biological characteristics, such as tumor heterogeneity, drug resistance, and microenvironment, but also to construct metastasis-related cell maps for predicting and monitoring the dynamics of metastasis. SCS is also used to identify therapeutic targets related to metastasis as it provides insights into the distribution of tumor cell subsets and gene expression differences between primary and metastatic tumors. Additionally, SCS techniques in combination with artificial intelligence (AI) are used in liquid biopsy to identify circulating tumor cells (CTCs), thereby providing a novel strategy for treating tumor metastasis. In this review, we summarize the potential applications of SCS in the field of tumor metastasis and discuss the prospects and limitations of SCS to provide a theoretical basis for finding therapeutic targets and mechanisms of metastasis.
Literature
1.
Chaffer CL, Weinberg RA. A perspective on cancer cell metastasis. Science. 2011;331(6024):1559–64.PubMedCrossRef
2.
3.
4.
Harper KL, Sosa MS, Entenberg D, Hosseini H, Cheung JF, Nobre R, et al. Mechanism of early dissemination and metastasis in Her2(+) mammary cancer. Nature. 2016;540(7634):588–92.PubMedPubMedCentralCrossRef
5.
Hosseini H, Obradovic MMS, Hoffmann M, Harper KL, Sosa MS, Werner-Klein M, et al. Early dissemination seeds metastasis in breast cancer. Nature. 2016;540(7634):552–8.PubMedPubMedCentralCrossRef
6.
7.
8.
Perone Y, Farrugia AJ, Rodríguez-Meira A, Győrffy B, Ion C, Uggetti A, et al. SREBP1 drives Keratin-80-dependent cytoskeletal changes and invasive behavior in endocrine-resistant ERα breast cancer. Nat Commun. 2019;10(1):3791–805.PubMedPubMedCentralCrossRef
9.
Chen YC, Sahoo S, Brien R, Jung S, Humphries B, Lee W, et al. Single-cell RNA-sequencing of migratory breast cancer cells: discovering genes associated with cancer metastasis. Analyst. 2019;144(24):7296–309.PubMedPubMedCentralCrossRef
10.
Bartoschek M, Oskolkov N, Bocci M, Lovrot J, Larsson C, Sommarin M, et al. Spatially and functionally distinct subclasses of breast cancer-associated fibroblasts revealed by single cell RNA sequencing. Nat Commun. 2018;9(1):5150–62.PubMedPubMedCentralCrossRef
11.
Andrews TS, Kiselev VY, McCarthy D, Hemberg M. Tutorial: guidelines for the computational analysis of single-cell RNA sequencing data. Nat Protoc. 2021;16(1):1–9.PubMedCrossRef
12.
13.
Li L, Xiong F, Wang Y, Zhang S, Gong Z, Li X, et al. What are the applications of single-cell RNA sequencing in cancer research: a systematic review. J Exp Clin Cancer Res. 2021;40(1):163–74.PubMedPubMedCentralCrossRef
14.
15.
Tang F, Barbacioru C, Wang Y, Nordman E, Lee C, Xu N, et al. mRNA-Seq whole-transcriptome analysis of a single cell. Nat Methods. 2009;6(5):377–82.PubMedCrossRef
16.
Islam S, Kjallquist U, Moliner A, Zajac P, Fan JB, Lonnerberg P, et al. Characterization of the single-cell transcriptional landscape by highly multiplex RNA-seq. Genome Res. 2011;21(7):1160–7.PubMedPubMedCentralCrossRef
17.
Ramsköld D, Luo S, Wang YC, et al. Full-length mRNA-Seq from single-cell levels of RNA and individual circulating tumor cells[J]. Nat Biotechnol. 2012;30(8):777–82.PubMedPubMedCentralCrossRef
18.
Picelli S, Bjorklund AK, Faridani OR, Sagasser S, Winberg G, Sandberg R. Smart-seq2 for sensitive full-length transcriptome profiling in single cells. Nat Methods. 2013;10(11):1096–8.PubMedCrossRef
19.
Azizi E, Carr AJ, Plitas G, Cornish AE, Konopacki C, Prabhakaran S, et al. Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment. Cell. 2018;174(5):1293–308.PubMedPubMedCentralCrossRef
20.
21.
Zhuo W, Xiaohan S, Qihui S. Advances in single-cell whole genome sequencing technology and its application in biomedicine. Yi Chuan. 2021;43(2):108–17.PubMed
22.
Bai X, Li Y, Zeng X, Zhao Q, Zhang Z. Single-cell sequencing technology in tumor research. Clin Chim Acta. 2021;518:101–9.PubMedCrossRef
23.
24.
Tian Y, Carpp LN, Miller HER, Zager M, Newell EW, Gottardo R. Single-cell immunology of SARS-CoV-2 infection. Nat Biotechnol. 2022;40(1):30–41.PubMedCrossRef
25.
Hashimshony T, Senderovich N, Avital G, Klochendler A, de Leeuw Y, Anavy L, et al. CEL-Seq2: sensitive highly-multiplexed single-cell RNA-Seq. Genome Biol. 2016;17(1):77–83.PubMedPubMedCentralCrossRef
26.
Zheng GX, Terry JM, Belgrader P, Ryvkin P, Bent ZW, Wilson R, et al. Massively parallel digital transcriptional profiling of single cells. Nat Commun. 2017;8:14049–60.PubMedPubMedCentralCrossRef
27.
Macosko EZ, Basu A, Satija R, Nemesh J, Shekhar K, Goldman M, et al. Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets. Cell. 2015;161(5):1202–14.PubMedPubMedCentralCrossRef
28.
Gierahn TM, Wadsworth MH 2nd, Hughes TK, Bryson BD, Butler A, Satija R, et al. Seq-Well: portable, low-cost RNA sequencing of single cells at high throughput. Nat Methods. 2017;14(4):395–8.PubMedPubMedCentralCrossRef
29.
Klein AM, Mazutis L, Akartuna I, Tallapragada N, Veres A, Li V, et al. Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells. Cell. 2015;161(5):1187–201.PubMedPubMedCentralCrossRef
30.
Yanai I, Hashimshony T. CEL-Seq2-single-cell RNA sequencing by multiplexed linear amplification. Methods Mol Biol. 2019;1979:45–56.PubMedCrossRef
31.
Ziegenhain C, Vieth B, Parekh S, Reinius B, Guillaumet-Adkins A, Smets M, et al. Comparative analysis of single-cell RNA sequencing methods. Mol Cell. 2017;65(4):631–43.PubMedCrossRef
32.
Zhang X, Li T, Liu F, Chen Y, Yao J, Li Z, et al. Comparative analysis of droplet-based ultra-high-throughput single-cell RNA-Seq systems. Mol Cell. 2019;73(1):130–42.PubMedCrossRef
33.
Aicher TP, Carroll S, Raddi G, Gierahn T, Wadsworth MH 2nd, Hughes TK, et al. Seq-Well: a sample-efficient, portable picowell platform for massively parallel single-cell RNA sequencing. Methods Mol Biol. 2019;1979:111–32.PubMedPubMedCentralCrossRef
34.
Zilionis R, Nainys J, Veres A, Savova V, Zemmour D, Klein AM, et al. Single-cell barcoding and sequencing using droplet microfluidics. Nat Protoc. 2017;12(1):44–73.PubMedCrossRef
35.
Choi JR, Yong KW, Choi JY, Cowie AC. Single-cell RNA sequencing and its combination with protein and DNA analyses. Cells. 2020;9(5):1130.PubMedCentralCrossRef
36.
Fu J, Akat KM, Sun Z, Zhang W, Schlondorff D, Liu Z, et al. Single-cell RNA profiling of glomerular cells shows dynamic changes in experimental diabetic kidney disease. J Am Soc Nephrol. 2019;30(4):533–45.PubMedPubMedCentralCrossRef
37.
Zhang F, Wei K, Slowikowski K, Fonseka CY, Rao DA, Kelly S, et al. Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. Nat Immunol. 2019;20(7):928–42.PubMedPubMedCentralCrossRef
38.
Farbehi N, Patrick R, Dorison A, Xaymardan M, Janbandhu V, Wystub-Lis K, et al. Single-cell expression profiling reveals dynamic flux of cardiac stromal, vascular and immune cells in health and injury. Elife. 2019;8:43882.CrossRef
39.
Farrell JA, Wang Y, Riesenfeld SJ, Shekhar K, Regev A, Schier AF. Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis. Science. 2018;360(6392):eaar3131.PubMedPubMedCentralCrossRef
40.
Wang J, Xu Y, Chen Z, Liang J, Lin Z, Liang H, et al. Liver immune profiling reveals pathogenesis and therapeutics for biliary atresia. Cell. 2020;183(7):1867–83.PubMedCrossRef
41.
Su T, Yang Y, Lai S, Jeong J, Jung Y, McConnell M, et al. Single-cell transcriptomics reveals zone-specific alterations of liver sinusoidal endothelial cells in cirrhosis. Cell Mol Gastroenterol Hepatol. 2021;11(4):1139–61.PubMedCrossRef
42.
Khateb M, Azriel A, Levi BZ. The third intron of IRF8 is a cell-type-specific chromatin priming element during mouse embryonal stem cell differentiation. J Mol Biol. 2019;431(2):210–22.PubMedCrossRef
43.
Wilk AJ, Rustagi A, Zhao NQ, Roque J, Martinez-Colon GJ, McKechnie JL, et al. A single-cell atlas of the peripheral immune response in patients with severe COVID-19. Nat Med. 2020;26(7):1070–6.PubMedPubMedCentralCrossRef
44.
Kim N, Kim HK, Lee K, Hong Y, Cho JH, Choi JW, Lee JI, Suh YL, Ku BM, Eum HH, et al. Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma. Nat Commun. 2020;11(1):2285–99.PubMedPubMedCentralCrossRef
45.
Zheng L, Qin S, Si W, Wang A, Xing B, Gao R, Ren X, Wang L, Wu X, Zhang J, et al. Pan-cancer single-cell landscape of tumor-infiltrating T cells. Science. 2012;374(6574):6474.CrossRef
46.
Fares J, Fares MY, Khachfe HH, Salhab HA, Fares Y. Molecular principles of metastasis: a hallmark of cancer revisited. Signal Transduct Target Ther. 2020;5(1):28–43.PubMedPubMedCentralCrossRef
47.
48.
49.
Wu XX, Yue GG, Dong JR, Lam CW, Wong CK, Qiu MH, et al. Actein Inhibits tumor growth and metastasis in HER2-positive breast tumor bearing mice via suppressing AKT/MTOR and RAS/RAF/MAPK signaling pathways. Front Oncol. 2020;10:854–68.PubMedPubMedCentralCrossRef
50.
Jin W. Role of JAK/STAT3 signaling in the regulation of metastasis, the transition of cancer stem cells, and chemoresistance of cancer by epithelial-mesenchymal transition. Cells. 2020;9(1):217–24.PubMedCentralCrossRef
51.
Ge X, Liu W, Zhao W, Feng S, Duan A, Ji C, et al. Exosomal transfer of LCP1 promotes osteosarcoma cell tumorigenesis and metastasis by activating the JAK2/STAT3 signaling pathway. Mol Ther Nucleic Acids. 2020;21:900–15.PubMedPubMedCentralCrossRef
52.
53.
Zhu HH, Zhu XY, Zhou MH, Cheng GY, Lou WH. Effect of WNT5A on epithelial-mesenchymal transition and its correlation with tumor invasion and metastasis in nasopharyngeal carcinoma. Asian Pac J Trop Med. 2014;7(6):488–91.PubMedCrossRef
54.
Yu M, Ting DT, Stott SL, Wittner BS, Ozsolak F, Paul S, et al. RNA sequencing of pancreatic circulating tumour cells implicates WNT signalling in metastasis. Nature. 2012;487(7408):510–3.PubMedPubMedCentralCrossRef
55.
Lin X, Xiaoqin H, Jiayu C, Li F, Yue L, Ximing X. Long non-coding RNA miR143HG predicts good prognosis and inhibits tumor multiplication and metastasis by suppressing mitogen-activated protein kinase and Wnt signaling pathways in hepatocellular carcinoma. Hepatol Res. 2019;49(8):902–18.PubMedCrossRef
56.
57.
Zhang F, Zhang H, Wang Z, Yu M, Tian R, Ji W, et al. P-glycoprotein associates with Anxa2 and promotes invasion in multidrug resistant breast cancer cells. Biochem Pharmacol. 2014;87(2):292–302.PubMedCrossRef
58.
Tomono T, Yano K, Ogihara T. Snail-induced epithelial-to-mesenchymal transition enhances P-gp-mediated multidrug resistance in HCC827 cells. J Pharm Sci. 2017;106(9):2642–9.PubMedCrossRef
59.
Zhang HC, Zhang F, Wu B, Han JH, Ji W, Zhou Y, et al. Identification of the Interaction between P-Glycoprotein and Anxa2 inMultidrug-resistant human breast cancer cells. Cancer Biol Med. 2012;9(2):99–104.PubMedPubMedCentral
60.
Ribelles N, Santonja A, Pajares B, Llacer C, Alba E. The seed and soil hypothesis revisited: current state of knowledge of inherited genes on prognosis in breast cancer. Cancer Treat Rev. 2014;40(2):293–9.PubMedCrossRef
61.
Hoshino A, Costa-Silva B, Shen TL, Rodrigues G, Hashimoto A, Tesic Mark M, et al. Tumour exosome integrins determine organotropic metastasis. Nature. 2015;527(7578):329–35.PubMedPubMedCentralCrossRef
62.
63.
Zhang HG, Grizzle WE. Exosomes: a novel pathway of local and distant intercellular communication that facilitates the growth and metastasis of neoplastic lesions. Am J Pathol. 2014;184(1):28–41.PubMedPubMedCentralCrossRef
64.
Pastushenko I, Blanpain C. EMT transition states during tumor progression and metastasis. Trends Cell Biol. 2019;29(3):212–26.PubMedCrossRef
65.
Calon A, Lonardo E, Berenguer-Llergo A, Espinet E, Hernando-Momblona X, Iglesias M, et al. Stromal gene expression defines poor-prognosis subtypes in colorectal cancer. Nat Genet. 2015;47(4):320–9.PubMedCrossRef
66.
67.
Lin Y, Xu J, Lan H. Tumor-associated macrophages in tumor metastasis: biological roles and clinical therapeutic applications. J Hematol Oncol. 2019;12(1):76–91.PubMedPubMedCentralCrossRef
68.
Fu LQ, Du WL, Cai MH, Yao JY, Zhao YY, Mou XZ. The roles of tumor-associated macrophages in tumor angiogenesis and metastasis. Cell Immunol. 2020;353:104119.PubMedCrossRef
69.
Wang D, Wang X, Si M, Yang J, Sun S, Wu H, et al. Exosome-encapsulated miRNAs contribute to CXCL12/CXCR4-induced liver metastasis of colorectal cancer by enhancing M2 polarization of macrophages. Cancer Lett. 2020;474:36–52.PubMedCrossRef
70.
Li K, Kang H, Wang Y, Hai T, Rong G, Sun H. Letrozole-induced functional changes in carcinoma-associated fibroblasts and their influence on breast cancer cell biology. Med Oncol. 2016;33(7):64–74.PubMedCrossRef
71.
Jayanthi P, Varun BR, Selvaraj J. Epithelial-mesenchymal transition in oral squamous cell carcinoma: An insight into molecular mechanisms and clinical implications. J Oral Maxillofac Pathol. 2020;24(1):189–92.PubMedPubMedCentralCrossRef
72.
Foroni C, Broggini M, Generali D, Damia G. Epithelial-mesenchymal transition and breast cancer: role, molecular mechanisms and clinical impact. Cancer Treat Rev. 2012;38(6):689–97.PubMedCrossRef
73.
74.
Wu S, Zhang H, Fouladdel S, Li H, Keller E, Wicha MS, et al. Cellular, transcriptomic and isoform heterogeneity of breast cancer cell line revealed by full-length single-cell RNA sequencing. Comput Struct Biotechnol J. 2020;18:676–85.PubMedPubMedCentralCrossRef
75.
Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl j Med. 2012;366:883–92.PubMedPubMedCentralCrossRef
76.
Leung ML, Davis A, Gao R, Casasent A, Wang Y, Sei E, et al. Single-cell DNA sequencing reveals a late-dissemination model in metastatic colorectal cancer. Genome Res. 2017;27(8):1287–99.PubMedPubMedCentralCrossRef
77.
Lin W, Noel P, Borazanci EH, Lee J, Amini A, Han IW, et al. Single-cell transcriptome analysis of tumor and stromal compartments of pancreatic ductal adenocarcinoma primary tumors and metastatic lesions. Genome Med. 2020;12(1):80–93.PubMedPubMedCentralCrossRef
78.
Liu Y, Ye G, Huang L, Zhang C, Sheng Y, Wu B, et al. Single-cell transcriptome analysis demonstrates inter-patient and intra-tumor heterogeneity in primary and metastatic lung adenocarcinoma. Aging. 2020;12(21):21559–81.PubMedPubMedCentralCrossRef
79.
Okamoto T, duVerle D, Yaginuma K, Natsume Y, Yamanaka H, Kusama D, et al. Comparative analysis of patient-matched PDOs revealed a reduction in OLFM4-associated clusters in metastatic lesions in colorectal cancer. Stem Cell Reports. 2021;16(4):954–67.PubMedPubMedCentralCrossRef
80.
Davis RT, Blake K, Ma D, Gabra MBI, Hernandez GA, Phung AT, et al. Transcriptional diversity and bioenergetic shift in human breast cancer metastasis revealed by single-cell RNA sequencing. Nat Cell Biol. 2020;22(3):310–20.PubMedCrossRef
81.
Chaika NV, Yu F, Purohit V, Mehla K, Lazenby AJ, DiMaio D, et al. Differential expression of metabolic genes in tumor and stromal components of primary and metastatic loci in pancreatic adenocarcinoma. PLoS ONE. 2012;7(3):e32996.PubMedPubMedCentralCrossRef
82.
Zhou Y, Yang D, Yang Q, Lv X, Huang W, Zhou Z, et al. Single-cell RNA landscape of intratumoral heterogeneity and immunosuppressive microenvironment in advanced osteosarcoma. Nat Commun. 2020;11(1):6322–38.PubMedPubMedCentralCrossRef
83.
Ni X, Zhuo M, Su Z, Duan J, Gao Y, Wang Z, et al. Reproducible copy numbervariation patterns among single circulating tumor cells of lung cancer patients. Proc Natl Acad Sci U S A. 2013;110(52):21083–8.PubMedPubMedCentralCrossRef
84.
McGranahan N, Swanton C. Clonal heterogeneity and tumor evolution: past, present, and the future. Cell. 2017;168(4):613–28.PubMedCrossRef
85.
Suda K, Kim J, Murakami I, Rozeboom L, Shimoji M, Shimizu S, et al. Innate genetic evolution of lung cancers and spatial heterogeneity: analysis of treatment-naive lesions. J Thorac Oncol. 2018;13(10):1496–507.PubMedPubMedCentralCrossRef
86.
Ma KY, Schonnesen AA, Brock A, Van Den Berg C, Eckhardt SG, Liu Z, et al. Single-cell RNA sequencing of lung adenocarcinoma reveals heterogeneity of immune response-related genes. JCI Insight. 2019;4(4):e12138787.CrossRef
87.
Zhang AW, McPherson A, Milne K, Kroeger DR, Hamilton PT, Miranda A, et al. Interfaces of Malignant and Immunologic Clonal Dynamics in Ovarian Cancer. Cell. 2018;173(7):1755–69.PubMedCrossRef
88.
Jimenez-Sanchez A, Memon D, Pourpe S, Veeraraghavan H, Li Y, Vargas HA, et al. Heterogeneous tumor-immune microenvironments among differentially growing metastases in an ovarian cancer patient. Cell. 2017;170(5):927–38.PubMedPubMedCentralCrossRef
89.
Pan XW, Zhang H, Xu D, Chen JX, Chen WJ, Gan SS, et al. Identification of a novel cancer stem cell subpopulation that promotes progression of human fatal renal cell carcinoma by single-cell RNA-seq analysis. Int J Biol Sci. 2020;16(16):3149–62.PubMedPubMedCentralCrossRef
90.
Puram SV, Tirosh I, Parikh AS, Patel AP, Yizhak K, Gillespie S, et al. Single-cell transcriptomic analysis of primary and metastatic tumor ecosystems in head and neck cancer. Cell. 2017;171(7):1611–24.PubMedPubMedCentralCrossRef
91.
Karaayvaz M, Cristea S, Gillespie SM, Patel AP, Mylvaganam R, Luo CC, et al. Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq. Nat Commun. 2018;9(1):3588–97.PubMedPubMedCentralCrossRef
92.
Yates LR, Knappskog S, Wedge D, Farmery JHR, Gonzalez S, Martincorena I, et al. Genomic Evolution of Breast Cancer Metastasis and Relapse. Cancer Cell. 2017;32(2):169–84.PubMedPubMedCentralCrossRef
93.
Navin N, Kendall J, Troge J, Andrews P, Rodgers L, McIndoo J, et al. Tumour evolution inferred by single-cell sequencing. Nature. 2011;472(7341):90–4.PubMedPubMedCentralCrossRef
94.
Saunders NA, Simpson F, Thompson EW, Hill MM, Endo-Munoz L, Leggatt G, et al. Role of intratumoural heterogeneity in cancer drug resistance: molecular and clinical perspectives. EMBO Mol Med. 2012;4(8):675–84.PubMedPubMedCentralCrossRef
95.
Jordan NV, Bardia A, Wittner BS, Benes C, Ligorio M, Zheng Y, et al. HER2 expression identifies dynamic functional states within circulating breast cancer cells. Nature. 2016;537(7618):102–6.PubMedPubMedCentralCrossRef
96.
Poupon R, Chazouilleres O, Balkau B, Poupon RE. Clinical and biochemical expression of the histopathological lesions of primary biliary cirrhosis. UDCA-PBC Group J Hepatol. 1999;30(3):408–12.PubMedCrossRef
97.
Slotman GJ, Mohit T, Raina S, Swaminathan AP, Ohanian M, Rush BF Jr. The incidence of metastases after multimodal therapy for cancer of the head and neck. Cancer. 1984;54(9):2009–14.PubMedCrossRef
98.
Hjortland GO, Meza-Zepeda LA, Beiske K, Ree AH, Tveito S, Hoifodt H. Genome wide single cell analysis of chemotherapy resistant metastatic cells in a case of gastroesophageal adenocarcinoma. BMC Cancer. 2011;11:455–62.PubMedPubMedCentralCrossRef
99.
Eyler CE, Rich JN. Survival of the fittest: cancer stem cells in therapeutic resistance and angiogenesis. J Clin Oncol. 2008;26(17):2839–45.PubMedCrossRef
100.
Nguyen A, Yoshida M, Goodarzi H, Tavazoie SF. Highly variable cancer subpopulations that exhibit enhanced transcriptome variability and metastatic fitness. Nat Commun. 2016;7:11246–57.PubMedPubMedCentralCrossRef
101.
Miyamoto DT, Zheng Y, Wittner BS, Lee RJ, Zhu H, Broderick KT, et al. RNA-Seq of single prostate CTCs implicates noncanonical Wnt signaling in antiandrogen resistance. Science. 2015;349(6254):1351–6.PubMedPubMedCentralCrossRef
102.
Gujral TS, Chan M, Peshkin L, Sorger PK, Kirschner MW, MacBeath G. A noncanonical Frizzled2 pathway regulates epithelial-mesenchymal transition and metastasis. Cell. 2014;159(4):844–56.PubMedPubMedCentralCrossRef
103.
Iseri OD, Kars MD, Arpaci F, Atalay C, Pak I, Gunduz U. Drug resistant MCF-7 cells exhibit epithelial-mesenchymal transition gene expression pattern. Biomed Pharmacother. 2011;65(1):40–5.PubMedCrossRef
104.
Lee MC, Lopez-Diaz FJ, Khan SY, Tariq MA, Dayn Y, Vaske CJ, et al. Single-cell analyses of transcriptional heterogeneity during drug tolerance transition in cancer cells by RNA sequencing. Proc Natl Acad Sci USA. 2014;111(44):4726–35.CrossRef
105.
Prieto-Vila M, Usuba W, Takahashi RU, Shimomura I, Sasaki H, Ochiya T, et al. Single-cell analysis reveals a preexisting drug-resistant subpopulation in the luminal breast cancer subtype. Cancer Res. 2019;79(17):4412–25.PubMedCrossRef
106.
Nath B, Bidkar AP, Kumar V, Dalal A, Jolly MK, Ghosh SS, et al. Deciphering hydrodynamic and drug-resistant behaviors of metastatic EMT breast cancer cells moving in a constricted microcapillary. J Clin Med. 2019;8(8):1194–208.PubMedCentralCrossRef
107.
Ozawa PMM, Alkhilaiwi F, Cavalli IJ, Malheiros D, de Souza Fonseca Ribeiro EM, Cavalli LR. Extracellular vesicles from triple-negative breast cancer cells promote proliferation and drug resistance in non-tumorigenic breast cells. Breast Cancer Res Treat. 2018;172(3):713–23.PubMedPubMedCentralCrossRef
108.
109.
110.
111.
Franken A, Honisch E, Reinhardt F, Meier-Stiegen F, Yang L, Jaschinski S, et al. Detection of ESR1 mutations in single circulating tumor cells on estrogen deprivation therapy but not in primary tumors from metastatic luminal breast cancer patients. J MolDiagn. 2020;22(1):111–21.
112.
113.
Sun Z, Yang S, Zhou Q, Wang G, Song J, Li Z, et al. Emerging role of exosome-derived long non-coding RNAs in tumor microenvironment. Mol Cancer. 2018;17(1):82–90.PubMedPubMedCentralCrossRef
114.
115.
Arvanitis CD, Ferraro GB, Jain RK. The blood-brain barrier and blood-tumour barrier in brain tumours and metastases. Nat Rev Cancer. 2020;20(1):26–41.PubMedCrossRef
116.
Lee HO, Hong Y, Etlioglu HE, Cho YB, Pomella V, Van den Bosch B, et al. Lineage-dependent gene expression programs influence the immune landscape of colorectal cancer. Nat Genet. 2020;52(6):594–603.PubMedCrossRef
117.
Robinson DR, Wu YM, Lonigro RJ, Vats P, Cobain E, Everett J, et al. Integrative clinical genomics of metastatic cancer. Nature. 2017;548(7667):297–303.PubMedPubMedCentralCrossRef
118.
Li H, Courtois ET, Sengupta D, Tan Y, Chen KH, Goh JJL, et al. Referencecomponent analysis of single-cell transcriptomes elucidates cellular heterogeneity in human colorectal tumors. Nat Genet. 2017;49(5):708–18.PubMedCrossRef
119.
Bao X, Shi R, Zhao T, Wang Y, Anastasov N, Rosemann M, et al. Integrated analysis of single-cell RNA-seq and bulk RNA-seq unravels tumour heterogeneity plus M2-like tumour-associated macrophage infiltration and aggressiveness in TNBC. Cancer Immunol Immunother. 2021;70(1):189–202.PubMedCrossRef
120.
Winterhoff BJ, Maile M, Mitra AK, Sebe A, Bazzaro M, Geller MA, et al. Single cell sequencing reveals heterogeneity within ovarian cancer epithelium and cancer associated stromal cells. Gynecol Oncol. 2017;144(3):598–606.PubMedPubMedCentralCrossRef
121.
122.
Zhang Y, Song J, Zhao Z, Yang M, Chen M, Liu C, et al. Single-cell transcriptome analysis reveals tumor immune microenvironment heterogenicity and granulocytes enrichment in colorectal cancer liver metastases. Cancer Lett. 2020;470:84–94.PubMedCrossRef
123.
Kuipers J, Jahn K, Beerenwinkel N. Advances in understanding tumour evolution through single-cell sequencing. Biochim Biophys Acta Rev Cancer. 2017;1867(2):127–38.PubMedPubMedCentralCrossRef
124.
Gundem G, Van Loo P, Kremeyer B, Alexandrov LB, Tubio JMC, Papaemmanuil E, et al. The evolutionary history of lethal metastatic prostate cancer. Nature. 2015;520(7547):353–7.PubMedPubMedCentralCrossRef
125.
Han K, Wang F-W, Cao C-H, Ling H, Chen J-W, Chen R-X, et al. CircLONP2 enhances colorectal carcinoma invasion and metastasis through modulating the maturation and exosomal dissemination of microRNA-17. Molecular Cancer. 2020;19(1):60–77.PubMedPubMedCentralCrossRef
126.
Maynard A, McCoach CE, Rotow JK, Harris L, Haderk F, Kerr DL, et al. Therapy-induced evolution of human lung cancer revealed by single-cell RNA sequencing. Cell. 2020;182(5):1232–51.PubMedPubMedCentralCrossRef
127.
Xu K, Zhang W, Wang C, Hu L, Wang R, Wang C, et al. Integrative analyses of scRNA-seq and scATAC-seq reveal CXCL14 as a key regulator of lymph node metastasis in breast cancer. Hum Mol Genet. 2021;30(5):370–80.PubMedCrossRef
128.
Lawson DA, Bhakta NR, Kessenbrock K, Prummel KD, Yu Y, Takai K, et al. Single-cell analysis reveals a stem-cell program in human metastatic breast cancer cells. Nature. 2015;526(7571):131–5.PubMedPubMedCentralCrossRef
129.
Tirosh I, Izar B, Prakadan SM, Wadsworth MH 2nd, Treacy D, Trombetta JJ, et al. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science. 2016;352(6282):189–96.PubMedPubMedCentralCrossRef
130.
Zhang C, He H, Hu X, Liu A, Huang D, Xu Y, Chen L, Xu D. Development and validation of a metastasis-associated prognostic signature based on single-cell RNA-seq in clear cell renal cell carcinoma. Aging. 2019;11(22):10183–202.PubMedPubMedCentralCrossRef
131.
Aceto N, Bardia A, Miyamoto DT, Donaldson MC, Wittner BS, Spencer JA, et al. Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell. 2014;158(5):1110–22.PubMedPubMedCentralCrossRef
132.
Ting DT, Wittner BS, Ligorio M, Vincent Jordan N, Shah AM, Miyamoto DT, et al. Single-cell RNA sequencing identifies extracellular matrix gene expression by pancreatic circulating tumor cells. Cell Rep. 2014;8(6):1905–18.PubMedPubMedCentralCrossRef
133.
Shaham U, Stanton KP, Zhao J, Li H, Raddassi K, Montgomery R, Kluger Y. Removal of batch effects using distributionmatching residual networks. Bioinformatics. 2017;33:2539–46.PubMedPubMedCentralCrossRef
134.
Li X, Wang K, Lyu Y, Pan H, Zhang J, Stambolian D, Susztak K, Reilly MP, Hu G, Li M. Deep learning enables accurate clustering with batch effect removal in single-cell RNA-seq analysis. Nat Commun. 2020;11:2338–51.PubMedPubMedCentralCrossRef
135.
Elbashir MK, Ezz M, Mohammed M, Saloum SS. Lightweight convolutional neural network for breast cancer classification using RNA-seq gene expression data. IEEE Access. 2019;7:185338–48.CrossRef
136.
Ding J, Condon A, Shah SP. Interpretable dimensionality reduction of single cell transcriptome data with deep generative models. Nat Commun. 2018;9:1–13.CrossRef
137.
Barbie DA, Tamayo P, Boehm JS, Kim SY, Moody SE, Dunn IF, Schinzel AC, Sandy P, Meylan E, Scholl C, et al. Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature. 2009;462:108–12.PubMedPubMedCentralCrossRef
138.
Lauria A, Peirone S, Giudice MD, Priante F, Rajan P, Caselle M, Oliviero S, Cereda M. Identification of altered biological processes in heterogeneous RNA-sequencing data by discretization of expression profiles. Nucleic Acids Res. 2020;48:1730–47.PubMedCrossRef
139.
Chen R, Yang L, Goodison S, Sun Y. Deep-learning approach to identifying cancer subtypes using high-dimensional genomic data. Bioinformatics. 2020;36:1476–83.PubMedCrossRef
140.
Gao F, Wang W, Tan M, Zhu L, Zhang Y, Fessler E, Vermeulen L, Wang X. DeepCC: a novel deep learning-based framework for cancer molecular subtype classification. Oncogenesis. 2019;8(9):44–55.PubMedPubMedCentralCrossRef
141.
Cheng Q, Li J, Fan F, Cao H, Dai Z-Y, Wang Z-Y, Feng S-S. Identification and analysis of glioblastoma biomarkers based on single cell sequencing. Front Bioeng Biotechnol. 2020;8:167–73.PubMedPubMedCentralCrossRef
142.
Zhang J, Guan M, Wang Q, Zhang J, Zhou T, Sun X. Single-cell transcriptome-based multilayer network biomarker for predicting prognosis and therapeutic response of gliomas. Brief Bioinform. 2020;21:1080–97.PubMedCrossRef
143.
144.
Wang Y, He X, Nie H, Zhou J, Cao P, Ou C. Application of artificial intelligence to the diagnosis and therapy of colorectal cancer. Am J Cancer Res. 2020;10(11):3575–98.PubMedPubMedCentral
145.
Poudineh M, Aldridge PM, Ahmed S, Green BJ, Kermanshah L, Nguyen V, Tu C, Mohamadi RM, Nam RK, Hansen A, et al. Tracking the dynamics of circulating tumour cell phenotypes using nanoparticle-mediated magnetic ranking. Nat Nanotechnol. 2017;12(3):274–81.PubMedCrossRef
146.
Poonpanichakul T, Shiao MS, Jiravejchakul N, Matangkasombut P, Sirachainan E, Charoensawan V, et al. Capturing tumour heterogeneity in pre- and post-chemotherapy colorectal cancer ascites-derived cells using single-cell RNA-sequencing. Biosci Rep. 2021;41(12):BSR20212093.PubMedPubMedCentralCrossRef
147.
Joosse SA, Gorges TM, Pantel K. Biology, detection, and clinical implications of circulating tumor cells. EMBO Mol Med. 2015;7(1):1–11.PubMedCrossRef
148.
Su Z, Wang Z, Ni X, Duan J, Gao Y, Zhuo M, et al. Inferring the evolution and progression of small-cell lung cancer by single-cell sequencing of circulating tumor cells. Clin Cancer Res. 2019;25(16):5049–60.PubMedCrossRef
149.
Kwan TT, Bardia A, Spring LM, Giobbie-Hurder A, Kalinich M, Dubash T, et al. A digital RNA signature of circulating tumor cells predicting early therapeutic response in localized and metastatic breast cancer. Cancer Discov. 2018;8(10):1286–99.PubMedPubMedCentralCrossRef
150.
Powell AA, Talasaz AH, Zhang H, Coram MA, Reddy A, Deng G, et al. Single cell profiling of circulating tumor cells: transcriptional heterogeneity and diversity from breast cancer cell lines. PLoS ONE. 2012;7(5):e33788.PubMedPubMedCentralCrossRef
151.
Lohr JG, Adalsteinsson VA, Cibulskis K, Choudhury AD, Rosenberg M, Cruz-Gordillo P, et al. Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer. NatBiotechnol. 2014;32(5):479–84.
152.
Miyamoto DT, Lee RJ, Kalinich M, LiCausi JA, Zheng Y, Chen T, et al. An RNA-based digital circulating tumor cell signature is predictive of drug response and early dissemination in prostate cancer. Cancer Discov. 2018;8(3):288–303.PubMedPubMedCentralCrossRef
153.
Shih A, Menzin A, Whyte J. Single-cell RNA-seq analysis of primary tumor and corresponding metastatic lesion in high-grade serous ovarian cancer. Clin Cancer Res. 2018;24(15):1611–24.
154.
155.
Schulz M, Michels B, Niesel K, Stein S, Farin H, Rodel F, et al. Cellular and molecular changes of brain metastases-associated myeloid cells during disease progression and therapeutic response. Science. 2020;23(6):101178.
156.
He X, Kuang G, Wu Y, Ou C. Emerging roles of exosomal miRNAs in diabetes mellitus. Clin Transl Med. 2021;11(6):468–87.CrossRef
157.
Wu J, Zeng D, Zhi S, Ye Z, Qiu W, Huang N, Sun L, Wang C, Wu Z, Bin J, Liao Y, Shi M, Liao W. Single-cell analysis of a tumor-derived exosome signature correlates with prognosis and immunotherapy response. J Transl Med. 2021;19(1):381.PubMedPubMedCentralCrossRef
158.
Fathi M, Joseph R, Adolacion JRT, Martinez-Paniagua M, An X, Gabrusiewicz K, Mani SA, Varadarajan N. Single-cell cloning of breast cancer cells secreting specific subsets of extracellular vesicles. Cancers (Basel). 2021;13(17):4397.CrossRef
159.
Wang Y, Liang Y, Xu H, Zhang X, Mao T, Cui J, et al. Single-cell analysis of pancreatic ductal adenocarcinoma identifies a novel fibroblast subtype associated with poor prognosis but better immunotherapy response. Cell Discov. 2021;7(1):36–52.PubMedPubMedCentralCrossRef
160.
Wang R, Song S, Harada K, Ghazanfari Amlashi F, Badgwell B, Pizzi MP, et al. Multiplex profiling of peritoneal metastases from gastric adenocarcinoma identified novel targets and molecular subtypes that predict treatment response. Gut. 2020;69(1):18–31.PubMedCrossRef
161.
Fairfax BP, Taylor CA, Watson RA, Nassiri I, Danielli S, Fang H, et al. Peripheral CD8(+) T cell characteristics associated with durable responses to immune checkpoint blockade in patients with metastatic melanoma. Nat Med. 2020;26(2):193–9.PubMedPubMedCentralCrossRef
162.
Kim KT, Lee HW, Lee HO, Song HJ, da Jeong E, Shin S, et al. Application of single-cell RNA sequencing in optimizing a combinatorial therapeutic strategy in metastatic renal cell carcinoma. Genome Biol. 2016;17:80–96.PubMedPubMedCentralCrossRef
163.
Shapiro E, Biezuner T, Linnarsson S. Single-cell sequencing-based technologies will revolutionize whole-organism science. Nat Rev Genet. 2013;14(9):618–30.PubMedCrossRef
164.
165.
Rozenblatt-Rosen O, Regev A, Oberdoerffer P, Nawy T, Hupalowska A, Rood JE, et al. The human tumor atlas network: charting tumor transitions across space and time at single-cell resolution. Cell. 2020;181(2):236–49.PubMedPubMedCentralCrossRef
166.
Théry C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol. 2009;9(8):581–93.PubMedCrossRef
Metadata
Title
Single-cell sequencing: a promising approach for uncovering the mechanisms of tumor metastasis
Authors
Yingying Han
Dan Wang
Lushan Peng
Tao Huang
Xiaoyun He
Junpu Wang
Chunlin Ou
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2022
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-022-01280-w

Other articles of this Issue 1/2022

Journal of Hematology & Oncology 1/2022 Go to the issue

Review

Momelotinib: an emerging treatment for myelofibrosis patients with anemia

Correspondence

Randomized phase 2 trial of intravenous oncolytic virus JX-594 combined with low-dose cyclophosphamide in patients with advanced soft-tissue sarcoma

Correction

Correction to: A novel melittin nano-liposome exerted excellent anti-hepatocellular carcinoma efficacy with better biological safety

Research

A proteolysis-targeting chimera molecule selectively degrades ENL and inhibits malignant gene expression and tumor growth

Correction

Correction: Naturally derived indole alkaloids targeting regulated cell death (RCD) for cancer therapy: from molecular mechanisms to potential therapeutic targets

Review

Deciphering mechanisms of immune escape to inform immunotherapeutic strategies in multiple myeloma
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits