Sixia Zhong, Xiuli Zhang1 *, Yun Li, Meili Zhang and Huannan Cao
1Department of Basic Sciences, Changchun University of Science and Technology, Changchun 130600, Jilin Province, China
Correspondence to: Xiuli Zhang, Department of Basic Sciences, Changchun University of Science and Technology, Changchun 130600, Jilin Province, China
Received date: November 19, 2024; Accepted date:November 30, 2024; Published date: December 05, 2024
Citation: Xiuli Zhang, et al. Bibliometric Analysis of Research Trends and Hotspots in Circular RNAs and Breast Cancer (2002–2022), IJMRS @ PubScholars Group 2024;1(2):1-8
Copyright: ©2024 Xiuli Zhang, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.
ABSTRACT
A bibliometric analysis aims to evaluate research hotspots and emerging trends in breast cancer and circular RNA ,providing fresh perspectives for future research in this field.
Methods:
This study employs bibliometric analysis tools, including VOSviewer and CiteSpace, to examine the literature on breast cancer and circular RNAs published between 2002 and 2022. The analysis focuses on bibliometric characteristics such as publication volume, country/region distribution, institutional affiliations, publishing journals, citation frequency, H-index, and research hotspots.
Results:
Through a comprehensive review of the Web of Science database, 787 relevant publications were identified. Over the two decades, the number of articles has exhibited a growing trend. China leads in research output within this field, followed by significant contributions from institutions in the United States and Iran. Fang Lin is the most prolific author, with other notable contributors including Yang Burton B., Tang Hailin, Wang Xuehui, and Xie Xiaoming. The journals “Frontiers in Oncology” and “Molecular Cancer” have the highest number
of publications in this domain. Research on tumor cell proliferation and migration continues to be a major focus. Over time, keyword trends have shifted from terms like “cell growth,” “messenger RNAs,” and “biomarker” to “long noncoding RNAs” and “sponge,” reflecting ongoing advancements in the field. These emerging keywords suggest that “long noncoding RNAs” and “sponge” are poised to become key research areas in the future.
Conclusion:
Bibliometric analysis offers valuable insights into the research landscape of breast cancer and circular RNAs. Recent studies have increasingly focused on the mechanisms underlying breast cancer and the biological functions of circular RNAs, highlighting the growing significance of this research area.
Keywords:
Artificial Intelligence, Detection, Microorganisms, Microscopy
Introduction
– According to the World Health Organization, in 2020, 2.26 million women worldwide were diagnosed with breast cancer,
resulting in 685,000 deaths. By the end of 2020, 7.8 million women had been diagnosed with breast cancer in the past five years, making it the most common cancer type globally. It accounts for approximately 30% of all cancer cases and 15%
of female cancer deaths. Despite significant advances in early diagnosis, surgery, chemotherapy, radiotherapy, endocrine therapy, and targeted therapy, breast cancer remains the leading cause of cancer-related deaths among women in over 100 countries [1-5]. Circular RNAs (circRNAs) are single-stranded RNA transcripts without 5′ caps or 3′ polyadenylated tails, generated through back- splicing from
precursor mRNAs, and characterized by a covalently closed loop structure [6]. More than 40 years ago, viroids were first discovered as circular RNA molecules [7]. Subsequently,
circular RNAs were observed in the cytoplasm of eukaryotic cell lines through electron microscopy [8]. At that time, these molecules were considered “junk” produced by aberrant splicing events, with only the testisspecific circular RNAs from the Sex-determining Region Y
(Sry) gene in mouse testes thought to potentially have a function[9,10].In recent years, with the development of high- throughput sequencing technology (RNA-seq) and specific bioinformatics algorithms, thousands of circular RNAs have been identified in various species, including fungi, protozoa, plants, worms, fish, insects, and mammals [11-15]. Studies have found that certain circular RNAs exhibit cell- or tissue-specific expression in eukaryotes and display high stability and evolutionary conservation [16-18]. Evidence suggests that circular RNAs may play important roles in regulating gene expression through multiple mechanisms, such as acting as miRNA sponges, interacting with RNA-binding proteins, serving as intermediates in alternative splicing, templates for protein translation, and transcriptional regulators [19]. Recent research indicates that circular RNAs are involved in the pathological processes of many human
diseases, especially cancer [20-23]. Currently, the mechanisms of circular RNAs in breast cancer are not well understood. However, research on breast cancer and circular RNAs has rapidly developed over the past decade. Identifying new advancements and trends in the field has become challenging due to the rapid development of research on breast cancer and circular RNAs. Bibliometric analysis holds significant value in describing the current status, publication trends, and scientific output of researchers and institutions, as well as identifying future research hotspots [24]. Additionally, assessing the quality of relevant academic achievements is crucial for researchers, universities, and decision-makers in government departments, helping them to formulate strategies [25]. Bibliometric analysis provides a reliable basis for standardizing academic quality and offering useful information globally [26] To date, this method has been used to estimate research trends in various medical fields, such as heart transplantation and familial hypercholesterolemia, as well as in non-medical fields [27-29].
Therefore, this study collected quantitative and qualitative data in the field of breast cancer and circular RNAs research,identifying the most productive countries, institutions, authors, and journals based on the number of publications or citations. The research objective is to conduct the first comprehensive bibliometric analysis of breast cancer and circular RNAs research over the past decade. This will provide scholars entering or about to enter the field with new insights into the current status, emerging trends, and future research hotspots in breast cancer and circular RNAs research.
Materials and Methods
Data Source and Search Strategy
On October 14, 2023, a literature search was conducted using the online version of the Web of Science Core Collection (WoSCC, Clarivate Analytics, Philadelphia, PA) database. The WoSCC database is considered one of the most comprehensive, systematic, and authoritative sources worldwide, covering over 12,000 influential journals and encompassing high-quality literature in biomedical, natural, and social sciences. It is widely used for bibliometric analysis and research on scientific literature visualization [30,31]. The search parameters were set as follows: Topic: [circular RNA] and Topic: [breast cancer], Time span: (2002 to 2022); Literature types: (articles and reviews); Language limit: English. All records (including title, author, keywords, source, abstract, and references) were exported in plain text format.
The retrieval was conducted in one day (October 14, 2023) to avoid changes due to daily database updates.
Data Extraction and Analysis
All records retrieved from the WoSCC were independently downloaded by the author Sixiazhong and imported into Microsoft Excel 2016 for further data processing. Metrics such as the annual number of publications, countries / regions, source journals, institutions, authors, keywords, and citation frequencies were extracted and statistically analyzed. Additionally, the Impact Factor (IF) and classifications from the Journal Citation Reports (JCR) were used to evaluate the quality of scientific information. The IF
represents the average number of citations per article in a journal over the most recent two-year period [32]. JCR assigns each scientific journal to the appropriate IF category and ranks them within specific fields (Q1, Q2, Q3, and Q4) [33]. The IF and JCR classifications used in this study are based on 2022 data. Furthermore, the H-index was applied as another metric. The H-index is defined as the number of h papers published by a researcher that have each been cited at least h times, with a higher H-index indicating greater academic influence. The H-index is often regarded as an important indicator for evaluating a researcher’s scientific output and academic standing and is
also useful for assessing the academic output capacity of countries, institutions, or journals [34].
Visualized Analysis
Using VOSviewer 1.6.19 (Centre for Science and Technology Studies, Leiden University, The Netherlands), we created a visualization map where nodes represent countries, institutions, authors, or keywords, connected through coauthorship, citation, co-citation, and co-occurrence analysis. The size of each node is determined by the weight of the element, such as the number of publications, citations, or frequency of occurrences. Each node was assigned a color, with the same color indicating the same cluster, representing a collection of items with similar attributes within the network [35]. The links between nodes represent associations between elements, and the thickness of the links indicates the strength of these associations. Total Link Strength (TLS) was used to quantitatively assess the links. Similar analytical methods were employed to create visualization maps of highly cited documents, countries or regions, institutions, journals,
journals, and authors across different periods to depict the evolution of these elements. Additionally, VOSviewer was used to categorize keywords with high co-occurance frequencies into clusters and to create a density visualization map.
CiteSpace V (version 6.2.R4, Drexel University) was used to:(i) generate visual maps of the cited references network from the time zone view, and (ii) detect burst analysis of co-occurring keywords. The parameter settings for CiteSpace were as follows: time slice (2002-2022), with each slice being one year, item source (all selected), node type (one at a time), selection condition (50), pruning (Pathfinder), visualization (cluster view static, show merged networks). The detailed workflow of literature screening and data analysis is illustrated in
Publication Outputs and Citation Trends
Based on the growth trend shown in Figure 2, the study period was divided into three phases: (i) 2002-2011: Initial Phase, with in citation rate; (ii) 2012-2015: Slow Growth Phase, with annual publications ranging between 2-6, maintaining a stable growth rate; and (iii) 2016-2022: Rapid Development Phase. In 2020, the number of publications on circular RNAs and breast cancer exceeded 100 for the
first time. By 2021, the annual number of publications surpassed 200, with a total of 6,807 citations. As of the retrieval date, these publications have been cited 27,966 times, with an average of 35.53 citations per paper. In theInitial Phase, research in this field was relatively limited and underdeveloped, with a low number of citations. However,
Contributions of Countries
Among the 787 papers, researchers hail from 52 countries or regions. From 2002 to 2022, the top ten countries in terms of global article output are shown in Figure 3A. The majority of papers originate from China (612 papers, accounting for 77.76%), followed by the United States (51 papers, 6.48%), Iran (48 papers, 6.10%), India (24 papers, 3.05%), and Italy (21 papers, 2.67%) (Table 1). To ensure the reliability and statistical significance of the analysis, we set the VOSviewer parameters to include countries with at least five publications. A total of 52 countries were included, of which 21 met this threshold. The citation relationships between different countries/regions are shown in the citation network map (Figure 3B). Among the top ten countries in terms of citation count, China ranks highest (citations = 20,650), followed by the United States. (citations = 3,975), Canada (citations = 1,283), Singapore (citations = 1,192), and Italy (citations = 1,039), with the latter three having comparable citation counts (Figure 3C). In terms of the number of
cited documents, China ranks first (documents = 612), followed by the United States (documents = 51) and Iran (documents = 48) (Figure 3D). Among the top ten countries in terms of total link strength, China ranks highest (Total Link Strength, TLS = 2,207), followed by Iran (TLS = 620) and the United States (TLS = 522) (Figure 3E). China has the strongest connections with Iran and the United States, highlighting the leading positions of China and the United States in circular RNA and breast cancer research. The international collaboration map shows the close cooperative relationships between countries/regions (Figure 3F). China is at the center of circular RNA and breast cancer research, with the highest total link strength (TLS = 52), a total of 612 publications, and 20,650 citations. China has particularly strong ties with the United States, Iran, and Singapore.
Figure 3: (A) The top 10 countries in terms of article output on circular RNA and breast cancer research from 2002 to 2022. (B) Citation
network map showing the relationships between different countries/regions with at least five publications. (C) The top 10 countries by
citation count. (D) The top 10 countries by the number of cited documents. (E) The top 10 countries by total link strength of citations.(F)
Close cooperation relationships between countries/regions, with line thickness reflecting the frequency of cooperation. Thicker lines
indicate stronger cooperation.
Contributions of Organizations
The 787 articles were published by 852 institutions. The top ten high-output institutions, all from China, are shown in Table2. Nanjing Medical University (TP = 60) is the most prolific institution, followed by Sun Yat-sen University (TP = 42), Zhengzhou University (TP = 23), and Tongji University (TP = 21). Using VOSviewer, we created a network visualization of institutions that published more than five papers. Figure 4 displays the cooperation network among institutions, with 63 projects forming nine different colored clusters. In the ranking of the top ten institutions by total link strength (TLS) (Table 3), four institutions are from China: Nanjing Medical University (TLS= 53), Southeast University (TLS = 24), Sun Yat-sen University (TLS = 24), and Jilin University (TLS = 17). Nanjing Medical University has the highest total link strength (TLS = 53), followed by Southeast University (TLS = 24) and Sun Yat-sen University (TLS = 24), both with equal total link strength. Notably, Southeast University performs best in terms of the average number of citations per publication (CPP = 102.69), indicating its high impact in the field of circular RNA and breast cancer research
Authors and Co-cited Authors
A total of 4,038 authors contributed to the research output, with 3,454 authors having published only one article. To identify the most influential experts in the field of breast cancer and circular RNAs over the past twenty years, we ranked the top fifteen authors based on total publications (TP) and H-index. As shown in Table 4, Fang Lin from Anhui Agricultural University ranks first in terms of the number of papers (TP = 14, CPP = 17.71, H-index =
Using VOSviewer, we set the minimum number of published papers threshold to three and found that the most prolific authors also have tight collaboration networks (Figure 5A).
Set the minimum citation threshold to 40, creating a cocitation network of authors that includes 126 nodes, 7,737 links, and 4 clusters. (Figure 5B).
Journals and Co-cited Journals
The 787 articles on circular RNAs and breast cancer were published in 284 academic journals. The top ten highoutput journals published a total of 191 papers, accounting for approximately 24% of the total output (Table 5). “Frontiers in Oncology” and “Molecular Cancer” lead in total output (TP), but “Molecular Cancer” surpasses “Frontiers in Oncology” in total citations (TC = 2,877), average citations (AC = 106.56), H-index (H-index = 126), and impact factor (IF = 37.3), indicating its significant status in the field of circular RNAs and breast cancer.
Based on network analysis, the citation patterns of 61 journals were divided into seven clusters, forming a total of 801 links (Figure 6A). The co-citation relationships between different journals are shown in Figure 6B, which includes 232 items forming five clusters. “Molecular Cancer” has the highest co-citation count at 1,894 times, followed by “Nature” (1,491 times), “Cell” (1,362 times), and “Oncotarget” (1,329 times).
References and Co-cited References
To further explore development trends, we analyzed the ten most-cited documents during the study period (Table 6). These documents include one review and nine research papers, with total citation counts ranging from 103 to 266. The most-cited article is a 2013 study by Thomas B. Hansen (266 citations), followed by a 2013 study by Sebastian Memczak (261 citations). Both articles discuss how circular RNAs mediate protein translation expression by regulating the activity of miR-7, revealing previously unrecognized regulatory potential of
coding sequences. Overall, newly published articles have lower citation rates, so the current citation counts may underestimate their actual value.
Figure 7 presents a co-citation analysis based on CiteSpace, showing 172 documents cited more than five times annually in the field of breast cancer and circular RNAs. Visualizing these documents in a timeline analysis reflects the temporal characteristics of research hotspots in this field. Based on the log-likelihood ratio (LLR)
algorithm, nine cluster labels representing hot topics were selected (Table 7) and ranked in Figure 7. Along the dashed lines connecting each label, larger circles indicate higher citation frequencies, and warmer-colored lines indicate later publication dates.
Cluster 0 (breast cancer) and Cluster 5 (gene expression) appeared the earliest, indicating that early breast cancer research focused on gene expression. Cluster 3 (cancer therapy) and Cluster 4 (tumor suppression) are current research hot topics, reflecting the high current interest in tumor suppressor genes and cancer therapy.
Keywords Analysis of Research Hotspots
The co-occurrence frequency of keywords can indicate scientific hotspots within a specific research theme, serving as an important method for tracking scientific development. This study extracted 2,909 keywords from 787 articles and listed the top 20 keywords based on cooccurrence frequency using VOSviewer software, as shown in Table 8. First, a density map was generated using 72 keywords with co- occurrence frequencies exceeding 20 times, visually depicting the distribution of popular themes in the field. As shown in Figure 8A, “circular RNA,” “breast cancer,” “expression,” “proliferation,” “invasion,” and “metastasis” are significant elements of the density map. Next, a cluster analysis was performed on the selected keywords.
Cluster 3 (blue circles, 17 keywords): Focuses on the mechanisms of action of breast cancer and circular RNAs, with keywords including “activation,” “apoptosis,” “invasion,” and “proliferation.” Cluster 4 (yellow circle, 1 keyword): Labeled as “cell-proliferation.” Finally, we identified the top 10 potential keywords, which are considered indicators of research frontiers or emerging trends over time. As shown in Figure 8C, since 2018, the keywords with citation bursts include “biomarker” (7.69), “circhipk3” (3.59), “long noncoding RNAs” (3.92), and “sponge” (3.59). These keywords represent the research frontiers in the study of breast cancer and circular RNAs. H-index=56), followed by Yang, Burton B. from the University of Toronto (TP=11, CPP=91.82, H-index=58),
and Tang Hailin from Sun Yat-sen University (TP=11, CPP=85.45, H-index=52), who have played significant roles in this field. Additionally, Yang, Burton B. from the University of Toronto stands out in terms of single article citations (TP=11, CPP=91.82, H-index=58), contributing many highquality articles to this field.
Discussion
We conducted a bibliometric analysis of 787 documents related to breast cancer and circular RNAs from the WoSCC database, covering the period from 2002 to 2022. This analysis revealed several key insights. Firstly, this has been an active research field in recent years. From 2002 to 2015, there was almost no growth in the number of research
papers on breast cancer and circular RNAs globally. However, since 2016, there has been an explosive increase in the number of research papers in this field. Through bibliometric analysis of countries, institutions, authors, and journals, we observed changes in global research trends. China has the highest output of publications in this field, followed by the United States and Iran. All top ten highoutput institutions are from China, with most collaborative research conducted domestically. European countries have relatively close collaborations, while cooperation among other countries is limited. Notably, Nanjing Medical University, Sun Yat-sen University, and Southeast University have close ties. Strengthening international cooperation, removing academic barriers, and promoting the development of breast cancer and circular RNA research is crucial.
In the co-author analysis, Fang Lin from Anhui Agricultural University has published the most papers (TP=14, CPP=17.71, Among the top ten journals, except for “Frontiers in Oncology” (impact factor 4.7), “Cancer Management and Research” (impact factor 3.3), and “OncoTargets and Therapy” (impact factor 4), the remaining journals have relatively high impact factors (greater than 5.0). “Frontiers in Oncology” and “Molecular Cancer” tie for the first place in the number of papers (TP), but “Molecular Cancer” surpasses “Frontiers in Oncology” in total citations (TC=2877), average citations (AC=106.56), H-index (H-index=126), and impact factor (IF=37.3). Furthermore, “Molecular Cancer” has the highest cocitation count at 1,894 times, indicating its significant status in the field of circular RNAs and breast cancer. According to the 2022 JCR standards, among the top ten most active journals, six are classified as Q1, three as Q2, and one as Q3. The downregulation of circular RNA gene expression promotes the proliferation, invasion, and migration of non-small cell lung cancer (NSCLC) cells by regulating protein expression [36-38]. Circular RNAs also play significant roles in various cancers. In breast cancer, they promote the development of multiple myeloma the In the co-author analysis, Fang Lin from Anhui Agricultural University has published the most papers (TP=14, CPP=17.71, Among the top ten journals, except for “Frontiers in Oncology” (impact factor 4.7), “Cancer Management and Research” (impact factor 3.3), and “OncoTargets and Therapy” (impact factor 4), the remaining journals have relatively high impact factors (greater than 5.0). “Frontiers in Oncology” and “Molecular Cancer” tie for the first place in the number of papers (TP), but “Molecular Cancer” surpasses “Frontiers in Oncology” in total citations (TC=2877), average citations (AC=106.56), H-index (H-index=126), and impact factor (IF=37.3). Furthermore, “Molecular Cancer” has the highest cocitation count at 1,894 times, indicating its significant status in the field of circular RNAs and breast cancer. According to the 2022 JCR standards, among the top ten most active journals, six are classified as Q1, three as Q2, and one as Q3. The downregulation of circular RNA gene expression promotes the proliferation, invasion, and migration of non-small cell lung cancer (NSCLC) cells by regulating protein expression [36-38]. Circular RNAs also play significant roles in various cancers. In breast cancer, they promote the development of multiple myeloma the
through the miR-1180/yes-associated protein pathway and facilitate the progression of Mantle Cell Lymphoma via pathways involving three lncRNAs (MALAT1, NEAT1, and XIST), five microRNAs (hsa-miR-129-5p, hsa-miR-3163, hsamiR-4662a-5p, hsa-miR- 101-3p, and hsa-miR-186-5p), and five mRNAs (NOTCH1, FMR1, ABCB1, TWIST1, and VEGFA) [39,40]. Additionally, circular RNAs reduce the proliferation, invasion, and migration of Wilms tumor cells through the miR-145-5p pathway, inhibit the growth and migration of bladder cancer cells through the C-MYC pathway, and suppress the growth and migration of colon cancer cells through pathways involving miR-150-5p, c-Myc, cyclin D1, p53, caspase-3, PARP, PTEN, PI3K, AKT, JAK2, and STAT5 [41-43]. Circular RNAs also inhibit the growth of hepatocellular carcinoma through pathways involving miR892a and miR-328- 3p, HIF1AN, HDGF, PI3K-AKT, the Rapamycin kinase complex 1/β-catenin, NOTCH2, BIRC5, SURVIVIN, and MYC [44]. Circular RNAs regulate carcinogenesis and cancer progression by acting as microRNA sponges, encoding proteins, and interacting with proteins [45]. In breast cancer, researchers detected 3,093 circular RNAs, with 18 exhibiting differential expression between adriamycin (ADM)-resistant and parental MCF-7 cells. Through quantitative real-time polymerase chain reaction (qPCR) analysis, they found that Homo sapiens (hsa)_circ_0006528 was significantly upregulated in ADMresistant cancer cells. When the expression of hsa_circ_0006528 was inhibited by small interfering RNA, the sensitivity of breast cancer cells to ADM significantly increased. Concurrently, the downregulation of hsa_circ_0006528 was associated with increased expression of miRNA-7-5p. This suggests that the hsa_circ_0006528/miR7-5p/RAF1 axis plays a regulatory role in ADM-resistant breast cancer [46]. Additionally, circABCB10 has been reported to promote breast cancer proliferation and inhibit apoptosis by acting as a sponge for miRNA-1271 [47]. Studies have also found that the miR-1275- ATG7/ULK1-autophagic axis and miR-92b-3p pathway promote autophagy and proliferation of breast cancer cells, while the miR- 190a3p/TP53INP1 axis pathway induces apoptosis in triple negative breast cancer cells [22,48,49]. To our knowledge, this is the first bibliometric analysis of the literature on breast cancer and circular RNAs, describing milestones and trends over the past twenty years. The advantages of this analysis lie in its objectivity and its ability to demonstrate development directions in the field while highlighting areas that have not been thoroughly studied. However, several limitations exist. Firstly, our data is solely from the WoSCC database, excluding other databases (such as PubMed), printed publications, and video materials, which may result in the omission of certain articles. Secondly, our selective analysis of the characteristics of the information might overlook some key points and details. Lastly, bibliometric methods have inherent limitations and cannot correct for factors such as population size, overall research output, gross domestic product, and research investment resources. Nevertheless, we have attempted to comprehensively analyze the development and research content of breast cancer and circular RNAs, aiming to summarize the discipline and provide guidance during this period of rapid development in this field.
Conclusion
In summary, research on the mechanisms of breast cancer related to the biological functions of circular RNAs is increasing, with “Molecular Cancer” being the most influential journal in this field. China leads in both output and scientific impact. Among institutions, Nanjing Medical University is the top producer and also has the highest total link strength. Fang Lin from Anhui Agricultural University ranks first in the number of papers, while Yang, Burton B. from the University of Toronto has the highest number of citations per paper. The research hotspots in this field focus on “expression,” “proliferation,” “invasion,” and “metastasis.” The research is primarily based on basic studies, concentrating on animal and cellular levels. Future research directions include “biomarker,” “circhipk3,” “long noncoding RNAs,” and “sponge.”
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