Tumor microenvironment: new era in exosomal circRNA research - a bibliometric analysis

Hai-Quan Wang , Lu Zhang , Ming-Jie Li , Rong-Quan He , Di-Yuan Qin , Bin Li , Jian-Di Li , Ke-Jun Wu , Shi-De Li , Han He , Zhen-Bo Feng , Gang Chen

Extracellular Vesicles and Circulating Nucleic Acids ›› 2025, Vol. 6 ›› Issue (2) : 245 -66.

PDF
Extracellular Vesicles and Circulating Nucleic Acids ›› 2025, Vol. 6 ›› Issue (2) :245 -66. DOI: 10.20517/evcna.2024.102
Original Article

Tumor microenvironment: new era in exosomal circRNA research - a bibliometric analysis

Author information +
History +
PDF

Abstract

Aim: The domain of exosomal circRNAs has seen rapid growth over the past few years, yet a thorough synthesis of the scholarly contributions has been lacking. This study employs bibliometric analysis to uncover the focal points and trends in exosomal circRNA research.

Methods: We selected articles on exosomal circRNAs from the Web of Science Core Collection (WoSCC) and deployed VOSviewer for co-authorship and co-occurrence analysis. CiteSpace was tapped to calculate citation bursts for documents and keywords, generating a time-zone map. Additionally, the bibliometrix R package was employed to identify locally cited references and construct thematic maps and trend topics.

Results: The exosomal circRNA research field has produced 767 articles over the past decade. China and Fudan University lead in publication counts, ranking first among countries and institutions, respectively. The journal with the highest number of publications and citations is Molecular Cancer. Zhang Wei and Li Yan are the top contributors and the most co-cited authors, respectively. Analysis of the results suggests that research related to the tumor microenvironment (TAM) may be a recent research hotspot. Among the latest keywords, terms such as microenvironment, macrophage, mesenchymal stem cells, and ceRNA appear frequently. The keyword with the most recent citation burst is ceRNA. The latest trend topic is the macrophage, and mesenchymal stem cell is identified as an emerging theme.

Conclusion: This study elucidates the hotspots and trends in exosomal circRNA research through bibliometric analysis. Themes related to the TAM, especially directions involving macrophages, fibroblasts, and mesenchymal stem cells, will likely open a new chapter in exosomal circRNA research.

Keywords

Exosomes / circRNAs / TME / visualization / bibliometric

Cite this article

Download citation ▾
Hai-Quan Wang, Lu Zhang, Ming-Jie Li, Rong-Quan He, Di-Yuan Qin, Bin Li, Jian-Di Li, Ke-Jun Wu, Shi-De Li, Han He, Zhen-Bo Feng, Gang Chen. Tumor microenvironment: new era in exosomal circRNA research - a bibliometric analysis. Extracellular Vesicles and Circulating Nucleic Acids, 2025, 6(2): 245-66 DOI:10.20517/evcna.2024.102

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Kalluri R.The biology, function, and biomedical applications of exosomes.Science2020;367:eaau6977 PMCID:PMC7717626

[2]

van Niel G, D’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles.Nat Rev Mol Cell Biol2018;19:213-28

[3]

Braicu C,Monroig P,Berindan-Neagoe I.Exosomes as divine messengers: are they the Hermes of modern molecular oncology?.Cell Death Differ2015;22:34-45 PMCID:PMC4262777

[4]

Boriachek K,Möller A.Biological functions and current advances in isolation and detection strategies for exosome nanovesicles.Small2018;14:1702153

[5]

Kurywchak P,Kalluri R.The emerging roles of exosomes in the modulation of immune responses in cancer.Genome Med2018;10:23 PMCID:PMC5868069

[6]

Zamani P,Butler AE,Sahebkar A.The therapeutic and diagnostic role of exosomes in cardiovascular diseases.Trends Cardiovasc Med2019;29:313-23

[7]

Rajagopal C.The origin and functions of exosomes in cancer.Front Oncol2018;8:66 PMCID:PMC5869252

[8]

Paskeh MDA,Mirzaei S.Emerging role of exosomes in cancer progression and tumor microenvironment remodeling.J Hematol Oncol2022;15:83 PMCID:PMC9238168

[9]

Boukouris S.Exosomes in bodily fluids are a highly stable resource of disease biomarkers.Proteomics Clin Appl2015;9:358-67 PMCID:PMC5502131

[10]

Jeck WR.Detecting and characterizing circular RNAs.Nat Biotechnol2014;32:453-61 PMCID:PMC4121655

[11]

Sanger HL,Riesner D,Kleinschmidt AK.Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures.Proc Natl Acad Sci U S A1976;73:3852-6 PMCID:PMC431239

[12]

Hansen TB,Clausen BH.Natural RNA circles function as efficient microRNA sponges.Nature2013;495:384-8

[13]

Meng S,Feng Z.CircRNA: functions and properties of a novel potential biomarker for cancer.Mol Cancer2017;16:94 PMCID:PMC5440908

[14]

Huang XY,Huang J.Exosomal circRNA-100338 promotes hepatocellular carcinoma metastasis via enhancing invasiveness and angiogenesis.J Exp Clin Cancer Res2020;39:20 PMCID:PMC6979009

[15]

Wang J,Wang Y.circRNA-002178 act as a ceRNA to promote PDL1/PD1 expression in lung adenocarcinoma.Cell Death Dis2020;11:32 PMCID:PMC6965119

[16]

Huang X,Zhang J,Tang H.Circular RNAs in breast cancer diagnosis, treatment and prognosis.Oncol Res2023;32:241-9 PMCID:PMC10765117

[17]

Altesha MA,Khan A,Zheng X.Circular RNA in cardiovascular disease.J Cell Physiol2019;234:5588-600

[18]

Xu YX,Li X.Exosomal ncRNAs: novel therapeutic target and biomarker for diabetic complications.Pharmacol Res2022;178:106135

[19]

Wang J,Yang J,Xu D.Non-coding RNAs in rheumatoid arthritis: from bench to bedside.Front Immunol2019;10:3129 PMCID:PMC6997467

[20]

Kristensen LS,Stagsted LVW,Hansen TB.The biogenesis, biology and characterization of circular RNAs.Nat Rev Genet2019;20:675-91

[21]

Wang Y,Ma J.Exosomal circRNAs: biogenesis, effect and application in human diseases.Mol Cancer2019;18:116 PMCID:PMC6610963

[22]

Zhang F,Qian H,Xu W.Exosomal circRNA: emerging insights into cancer progression and clinical application potential.J Hematol Oncol2023;16:67 PMCID:PMC10294326

[23]

Liu X,Zhou S,Mei L.Circular RNA: an emerging frontier in RNA therapeutic targets, RNA therapeutics, and mRNA vaccines.J Control Release2022;348:84-94 PMCID:PMC9644292

[24]

Dance A.Circular logic: understanding RNA’s strangest form yet.Nature2024;635:511-3

[25]

Ren L,Mo L.Mechanisms of circular RNA degradation.Commun Biol2022;5:1355 PMCID:PMC9734648

[26]

Yi Y,Zeng H.Tumor-derived exosomal non-coding RNAs: the emerging mechanisms and potential clinical applications in breast cancer.Front Oncol2021;11:738945 PMCID:PMC8544822

[27]

Zhang L,Jiang ST.Worldwide research trends on tumor burden and immunotherapy: a bibliometric analysis.Int J Surg2024;110:1699-710 PMCID:PMC10942200

[28]

Shen Z,Chen Z.The global research of artificial intelligence on prostate cancer: a 22-year bibliometric analysis.Front Oncol2022;12:843735 PMCID:PMC8921533

[29]

Gong K,Liu W.Global research trends of Apolipoprotein E in central nervous system: a scientometric analysis.Int Immunopharmacol2021;98:107919

[30]

Zhu X,Tang X.A bibliometric analysis of non-coding RNA studies in acute pancreatitis.Medicine2024;103:e37486 PMCID:PMC10956959

[31]

Mongeon P.The journal coverage of Web of Science and Scopus: a comparative analysis.Scientometrics2016;106:213-28

[32]

AlRyalat SAS,Momani SM.Comparing bibliometric analysis using PubMed, Scopus, and Web of science databases.J Vis Exp2019;152:e58494

[33]

Eck NJ, Waltman L. Software survey: VOSviewer, a computer program for bibliometric mapping.Scientometrics2010;84:523-38 PMCID:PMC2883932

[34]

Chen C.Searching for intellectual turning points: progressive knowledge domain visualization.Proc Natl Acad Sci U S A2004;101:5303-10 PMCID:PMC387312

[35]

Wang S,Zheng L.Global trends in research of macrophages associated with acute lung injury over past 10 years: a bibliometric analysis.Front Immunol2021;12:669539 PMCID:PMC8173163

[36]

Pons P.Computing communities in large networks using random walks. In: Yolum p, Güngör T, Gürgen F, Özturan C, Editors. Computer and Information Sciences - ISCIS 2005. Springer, Berlin, Heidelberg; 2005. pp. 284-93.

[37]

Roldan-Valadez E,Ibarra-Contreras R.Current concepts on bibliometrics: a brief review about impact factor, Eigenfactor score, CiteScore, SCImago Journal Rank, Source-Normalised Impact per Paper, H-index, and alternative metrics.Ir J Med Sci2019;188:939-51

[38]

Chen C.Science mapping: a systematic review of the literature.J Data Inf Sci2017;2:1-40

[39]

Bertoli-Barsotti L.A theoretical model of the relationship between the h-index and other simple citation indicators.Scientometrics2017;111:1415-48 PMCID:PMC5438441

[40]

Chen C.CiteSpace II: detecting and visualizing emerging trends and transient patterns in scientific literature.J Am Soc Inf Sci2006;57:359-77

[41]

Li Y,Bao C.Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis.Cell Res2015;25:981-4 PMCID:PMC4528056

[42]

Li S,Chen B.exoRBase: a database of circRNA, lncRNA and mRNA in human blood exosomes.Nucleic Acids Res2018;46:D106-12 PMCID:PMC5753357

[43]

Bo X,Chen S.Evidence and perspectives on miRNA, circRNA, and lncRNA in myocardial ischemia-reperfusion injury: a bibliometric study.J Cardiothorac Surg2025;20:66 PMCID:PMC11736979

[44]

Wang Y,Zhao R.CircUbe3a from M2 macrophage-derived small extracellular vesicles mediates myocardial fibrosis after acute myocardial infarction.Theranostics2021;11:6315-33 PMCID:PMC8120198

[45]

Fan L,Li Z.Exosome-based mitochondrial delivery of circRNA mSCAR alleviates sepsis by orchestrating macrophage activation.Adv Sci2023;10:e2205692 PMCID:PMC10190648

[46]

Memczak S,Elefsinioti A.Circular RNAs are a large class of animal RNAs with regulatory potency.Nature2013;495:333-8

[47]

McAndrews KM,Kalluri R.Mouse models to evaluate the functional role of the tumor microenvironment in cancer progression and therapy responses.Cold Spring Harb Perspect Med2024;14:a041411 PMCID:PMC11216184

[48]

Kalluri R.The role of extracellular vesicles in cancer.Cell2023;186:1610-26 PMCID:PMC10484374

[49]

Zhang SJ,Li CP.Identification and characterization of circular RNAs as a new class of putative biomarkers in diabetes retinopathy.Invest Ophthalmol Vis Sci2017;58:6500-9

[50]

Bahn JH,Li F.The landscape of microRNA, Piwi-interacting RNA, and circular RNA in human saliva.Clin Chem2015;61:221-30 PMCID:PMC4332885

[51]

Hou JC,Zhong SL.Circular RNA circASS1 is downregulated in breast cancer cells MDA-MB-231 and suppressed invasion and migration.Epigenomics2019;11:199-213

[52]

Lyu ZZ,Yang MY,Yang Z.Exosome-mediated transfer of circRNA563 promoting hepatocellular carcinoma by targeting the microRNA148a-3p/metal-regulatory transcription factor-1 pathway.World J Gastroenterol2023;29:6060-75 PMCID:PMC10731156

[53]

Tao X,Lu R.Clinical significance of hsa_circ_0000419 in gastric cancer screening and prognosis estimation.Pathol Res Pract2020;216:152763

[54]

Pan Z,Zhang J.A novel protein encoded by exosomal circATG4B induces oxaliplatin resistance in colorectal cancer by promoting autophagy.Adv Sci2022;9:e2204513 PMCID:PMC9762280

[55]

Tiwari A,Lin SY.Tumor microenvironment: barrier or opportunity towards effective cancer therapy.J Biomed Sci2022;29:83 PMCID:PMC9575280

[56]

Wang D,Lyu M,Zhong S.Circular RNA HSDL2 promotes breast cancer progression via miR-7978 ZNF704 axis and regulating hippo signaling pathway.Breast Cancer Res2024;26:105 PMCID:PMC11210124

[57]

Chen J,Xu J.CircZFR promotes colorectal cancer progression via stabilizing BCLAF1 and regulating the miR-3127-5p/RTKN2 axis.Sci China Life Sci2024;67:1881-98

[58]

Dilsiz N.A comprehensive review on recent advances in exosome isolation and characterization: toward clinical applications.Transl Oncol2024;50:102121 PMCID:PMC11418158

[59]

Guo X,Yang DH.Exosomal circular RNAs: a chief culprit in cancer chemotherapy resistance.Drug Resist Updat2023;67:100937

[60]

Zhang X,Wang H.Circular RNA circNRIP1 acts as a microRNA-149-5p sponge to promote gastric cancer progression via the AKT1/mTOR pathway.Mol Cancer2019;18:20 PMCID:PMC6360801

[61]

de Visser KE, Joyce JA. The evolving tumor microenvironment: from cancer initiation to metastatic outgrowth.Cancer Cell2023;41:374-403

[62]

Han QF,Hu KS.Exosome biogenesis: machinery, regulation, and therapeutic implications in cancer.Mol Cancer2022;21:207 PMCID:PMC9623991

[63]

Cunha E Rocha K,Olefsky JM.Exosome-mediated impact on systemic metabolism.Annu Rev Physiol2024;86:225-53

[64]

Li J,Liu CG.The potential role of exosomal circRNAs in the tumor microenvironment: insights into cancer diagnosis and therapy.Theranostics2022;12:87-104 PMCID:PMC8690929

[65]

Yunna C,Lei W.Macrophage M1/M2 polarization.Eur J Pharmacol2020;877:173090

[66]

Boutilier AJ.Macrophage polarization states in the tumor microenvironment.Int J Mol Sci2021;22:6995 PMCID:PMC8268869

[67]

Hu X,Wang L.Crosstalk among Jak-STAT, Toll-like receptor, and ITAM-dependent pathways in macrophage activation.J Leukoc Biol2007;82:237-43

[68]

Huang X,Guan J.Exosomal circsafb2 reshaping tumor environment to promote renal cell carcinoma progression by mediating M2 macrophage polarization.Front Oncol2022;12:808888 PMCID:PMC9133324

[69]

Du A,Sun X.Exosomal circRNA-001264 promotes AML immunosuppression through induction of M2-like macrophages and PD-L1 overexpression.Int Immunopharmacol2023;124:110868

[70]

Gu X,Dong M,Yang J.Exosomal transfer of tumor-associated macrophage-derived hsa_circ_0001610 reduces radiosensitivity in endometrial cancer.Cell Death Dis2021;12:818 PMCID:PMC8405633

[71]

Zhuang M,Ji J.Exosomal circ-0100519 promotes breast cancer progression via inducing M2 macrophage polarisation by USP7/NRF2 axis.Clin Transl Med2024;14:e1763 PMCID:PMC11303452

[72]

Song J,He S.Exosomal hsa_circ_0017252 attenuates the development of gastric cancer via inhibiting macrophage M2 polarization.Hum Cell2022;35:1499-511

[73]

Bryja A,Farzaneh M.Small extracellular vesicles - a host for advanced bioengineering and “Trojan Horse” of non-coding RNAs.Life Sci2023;332:122126

[74]

Pittenger MF,Beck SC.Multilineage potential of adult human mesenchymal stem cells.Science1999;284:143-7

[75]

Li QY,Huang YK.Role of noncoding RNAs in liver fibrosis.World J Gastroenterol2023;29:1446-59 PMCID:PMC10044853

[76]

Wang C,Wu R.Mesenchymal stem cell-derived exosomes and non-coding RNAs: regulatory and therapeutic role in liver diseases.Biomed Pharmacother2023;157:114040

[77]

Shi Y,Lin L.Tumour-associated mesenchymal stem/stromal cells: emerging therapeutic targets.Nat Rev Drug Discov2017;16:35-52

[78]

Nicodemou A,Čeháková M.Emerging roles of mesenchymal stem/stromal-cell-derived extracellular vesicles in cancer therapy.Pharmaceutics2023;15:1453 PMCID:PMC10221697

[79]

Liu J,Li S.The biology, function, and applications of exosomes in cancer.Acta Pharm Sin B2021;11:2783-97 PMCID:PMC8463268

[80]

Ba L,Li X.Gastric cancer cell-derived exosomes can regulate the biological functions of mesenchymal stem cells by inducing the expression of circular RNA circ_0004303.Stem Cells Dev2021;30:830-42

[81]

Li W,Zheng P,Zhao S.The origins and generation of cancer-associated mesenchymal stromal cells: an innovative therapeutic target for solid tumors.Front Oncol2021;11:723707 PMCID:PMC8427299

[82]

Mao X,Wang W.Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives.Mol Cancer2021;20:131 PMCID:PMC8504100

[83]

Jiang Q,Wang Z.Tumor-associated fibroblast-derived exosomal circDennd1b promotes pituitary adenoma progression by modulating the miR-145-5p/ONECUT2 axis and activating the MAPK pathway.Cancers2023;15:3375 PMCID:PMC10340501

[84]

Shi H,Qin M.Exosomal circ_0088300 derived from cancer-associated fibroblasts acts as a miR-1305 sponge and promotes gastric carcinoma cell tumorigenesis.Front Cell Dev Biol2021;9:676319 PMCID:PMC8188357

[85]

Chen Y,Kalluri R.Clinical and therapeutic relevance of cancer-associated fibroblasts.Nat Rev Clin Oncol2021;18:792-804 PMCID:PMC8791784

[86]

Zhou Y,Zhuo H.Cancer-associated fibroblast exosomes promote chemoresistance to cisplatin in hepatocellular carcinoma through circZFR targeting signal transducers and activators of transcription (STAT3)/ nuclear factor -kappa B (NF-κB) pathway.Bioengineered2022;13:4786-97 PMCID:PMC8973934

[87]

Du J,Yang M.NGR-modified CAF-derived exos targeting tumor vasculature to induce ferroptosis and overcome chemoresistance in osteosarcoma.Adv Sci2025;12:e2410918 PMCID:PMC11948032

[88]

Biffi G,Spielman B.IL1-induced JAK/STAT signaling is antagonized by TGFβ to shape CAF heterogeneity in pancreatic ductal adenocarcinoma.Cancer Discov2019;9:282-301 PMCID:PMC6368881

[89]

Payervand N,Razmara E.Exosomal circ_0084043 derived from colorectal cancer-associated fibroblasts promotes in vitro endothelial cell angiogenesis by regulating the miR-140-3p/HIF-1α/VEGF signaling axis.Heliyon2024;10:e31584 PMCID:PMC11140710

[90]

Zhu W,Tang L.Identification of a plasma exosomal lncRNA- and circRNA-based ceRNA regulatory network in patients with lung adenocarcinoma.Clin Respir J2024;18:e70026 PMCID:PMC11491303

[91]

Wang X,Wu Z,Shi Y.Machine learning-based comparative analysis of pan-cancer and pan-normal tissues identifies pan-cancer tissue-enriched circRNAs related to cancer mutations as potential exosomal biomarkers.Front Oncol2021;11:703461 PMCID:PMC8479194

[92]

Ma C,Peng A.Pan-cancer spatially resolved single-cell analysis reveals the crosstalk between cancer-associated fibroblasts and tumor microenvironment.Mol Cancer2023;22:170 PMCID:PMC10571470

[93]

Pei Y,Wang W.Extracellular vesicles as a new frontier of diagnostic biomarkers in osteosarcoma diseases: a bibliometric and visualized study.Front Oncol2024;14:1359807 PMCID:PMC10944918

[94]

Zhou Z,Han B.Circular RNA in cholangiocarcinoma: a systematic review and bibliometric analysis.Pathol Res Pract2023;249:154755

[95]

Pranckutė R.Web of Science (WoS) and Scopus: the Titans of bibliographic information in today’s academic world.Publications2021;9:12

AI Summary AI Mindmap
PDF

102

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/