We conducted a literature search on the Web of Science Core Collection (WoSCC) database (https://www.webofscience.com/wos/woscc/advanced-search) on February 8, 2024. The search formula is ((TS = (Osteosarcom)) AND TS = ((“lncRNA” OR “lnc RNA” OR “long ncRNA” OR “long noncoding RNA” OR “long non coding RNA” OR “long non translated RNA” OR “long non protein coding RNA” OR “linc RNA” OR “lincRNA” OR “microRNA” OR “micro RNA” OR “mi RNA” OR “miR” OR “circRNA” OR “circ RNA” OR “circular RNA” OR “circular noncoding RNA” OR “circular non coding RNA” OR “circular ncRNA” OR “circular ncRNA” OR “circular nonprotein coding RNA” OR “circular nontranslated RNA” OR “circular untranslated RNA” OR “ribosomal RNA” OR “rRNA” OR “transfer RNA” OR “tRNA” OR “tRNA-derived small RNAs” OR “tsRNA” OR “Piwi-interacting RNA” OR “PiRNA” OR “small nucleolar RNA” OR “snoRNA” OR “small nuclear RNA” OR “snRNA” OR “tRNA-Derived Fragments” OR “tRF” OR “tRNA halves” OR “tiRNA” OR “small interfering RNA” OR “siRNA” OR “small cytoplasmic RNA” OR “scRNA”)) AND LA = (English) AND DOP = (2001-01-01/2023-12-31)AND DT = (Article OR Review) ( Figure 1 ).

Software for bibliometrics analysis, VOSViewer (version 1.6.20), is used to extract data and information from the literature (20). The size, color, and line thickness of each node in the VOS viewer-generated chart correspond to the quantity and classification of the items they represent, respectively, and the degree of collaboration or co-citation between them. Each node represents a project (21, 22). We use it to establish a network of cooperation, co-citation and co-occurrence (23, 24). In our research, the software mainly completes the following analysis: national and institutional analysis, journal and co-citation journal analysis, author and co-citation author analysis, keyword co-occurrence analysis.

Another program created by Professors Chen C for bibliometric analysis and visualization is CiteSpace (version 6.2.R6) (25). CiteSpace was used in our study to map the journals’ dual-map overlay and to evaluate references using Citation Bursts.

According to the Journal Citation report 2022, we provide a summary of the periodical division and Influence factors. In addition, a quantitative analysis of the publication is performed using Microsoft Office Excel 2021.

There were 3,642 studies on ncRNAs of OS in the past 23 years, including 3,321 “articles” and 321 “reviews”. As shown in Figure 2 , the number of publications was 0 before 2008, and there were no related research publications. Since 2014 the number of posts has increased rapidly. The number of publications in 2020 was 512, 2.0 times that of 2016. From the trend chart, we can see that the research on OS ncRNAs are mainly concentrated in the past 10 years, reaching a peak at the end of 2020. The number of publications declined in 2021-2023. The specific reason for the decline is not very clear, preliminary speculation may be related to the outbreak of COVID-19. In addition, the cumulative number of articles in the past 23 years showed an upward trend.

Publications from 57 countries and 2,631 institutions were included in the study. The distribution of the top ten countries is shown in Table 1 . Among these countries, China has the largest number of publications (n = 3,084, 84.68%), followed by the United States (n = 289, 7.94%). Then, depending on the quantity of publications in each nation, we created a collaborative network using a visual analysis of 38 countries related to publications ( Figure 3 ). It is important to note that there will be variations in the level of collaboration between various nations. For example, China has close cooperation with United States, Germany, Canada, United Kingdom and Australia. The United States also actively cooperates with Israel, Chile, Canada and Italy. From the perspective of time scale, the average number of papers published in the United States, United Kingdom, Germany and Singapore are mainly concentrated in 2016. The research in China, Turkey, Sweden and Austria are mainly concentrated in 2018, which started relatively late.

From Table 1 , we can see that Chinese research institutions publish the most research results. The four institutions with the largest number of publications are: Nanjing Medical University (129, 3.54%), Shanghai Jiao Tong University (128, 3.51%), Zhengzhou University (110, 3.02%) and China Medical University (109, 2.99%). Then, we set the screening criteria to analyze 125 institutions and build a cooperative network according to the number of publications and partnerships of each institution ( Figure 4 ). As shown in Figure 4 , there is a close cooperative relationship among Shanghai Jiao Tong University, Tongji University and Fudan University. The Massachusetts General Hospital, Harvard University, Huazhong University of Science and Technology, and Zhengzhou University also cooperate actively.

After screening the literature, we found that the papers on ncRNAs in OS were published in 553 journals. Oncology Letters published most of the journals (n = 139, 3.82%), followed by European Review for Medical and Pharmacological Sciences (120, 3.31%) and Molecular Medicine Reports (n = 95, 2.61%) ( Table 2 ). Among these journals, the journal with the highest impact factor is Biomedicine & Pharmacotherapy (IF = 7.5), followed by Cancer Cell International (IF = 5.8) ( Table 2 ). Then, we selected 140 journals to draw a journal network (set the minimum number of publications to be 5). As shown in Figure 5A , Oncology letters has an active citation relationship with journals such as European Review, Medical on oncology, Cellular physiology and biochemistry and so on.

There are 3 journals that have been cited more than 3,000 times ( Table 2 ). Oncotarget (Co-Citation = 4,268) is the most frequently cited journal, followed by Cancer Research (Co-Citation = 3,500) and Plos One (Co-Citation = 3,378). In addition, the influencing factor of Nature was the highest (IF = 64.8), followed by Cell (IF = 64.5). As shown in Figure 5 , we draw a co-citation network diagram after screening (set the number of citations to at least 80) ( Figure 5B ). Oncotarget has a positive co-citation relationship with Tumor Biology, Cancer Research, Oncology Letters and Molecular Cancer. Cell has a positive co-citation relationship with Nature, Cancer Research, Molecular Cancer Plos one and so on.

The double map superposition of periodicals can see the common research hotspots in the two fields, so we use the double map superposition of periodicals to show the citation relationship between journals and co-cited journals. On the left is the citation journal clustering, and the cited journal clustering is on the right (26). In Figure 6 , the yellow line is thicker, indicating that it is the main citation path, which represents the research of ncRNAs in OS is published in Molecular/Biology/immunology journals mainly cited by Molecular/Biology/Genetics journals, of which Oncotarget is the most frequently cited. In addition, another green path indicates that the research of OS ncRNAs published in Molecular/Medicine/Medical/Clinical journals cited by Molecular/Biology/Genetics journals.

We extracted the author information from the literature and found that a total of 15,631 authors participated in the study of ncRNA in OS. The top three authors have published more than 30 articles ( Table 3 ). We have established a cooperative network (set the number of published papers to be greater than or equal to 7 ( Figure 7A ). We have observed some partnerships. For example, Wei Liu, Wei Zhang, Bin Wang, Kun Wang, Yang Cao, Yang Wang, etc have close cooperation. Wei Zhang, Hao Li, Ming Liu, Yi Liu, Yong Zhang, Lu Zhang actively cooperates.

There are 49,777 co-cited authors. Among the top 10 co-cited authors, 5 authors have been cited more than 400 times ( Table 3 ). The most co-cited author is Wang Y (n = 676), followed by Bartel DP (n = 488), Mirabello I (n = 474), Ottaviani G (n = 453) and Zhang Y (n = 431). We set the minimum number of co-citations equal to 40 to screen co-cited authors, and then draw a co-citation network diagram. ( Figure 7B ). As shown in Figure 7B , Wang Y, Zhu KB, Li ZW and other authors have a positive cooperative relationship.

Over the past decade, there have been 85,361 co-cited references on ncRNA studies in OS. The top 10 co-cited references listed in Table 4 have all received at least 160 co-citations. We have constructed a co-citation network diagram (setting the number of co-citations greater than or equal to 30) ( Figure 8 ). “Ottaviani G, 2009, Cancer Treatment and Research” shows active co-cited relationships with “Mirabello I, 2009, Cancer”, “Bartel DP, 2004, Cell”, “Jones KB, 2012, Cancer Research”, etc.

Reference with citation bursts refers to the literature that is often cited in this field for a period of time. In our study, CiteSpace identified 20 references with strongly cited outbreaks ( Figure 9 ). Our research shows that citation bursts for references occurred as early as 2008 and lasted until 2023. As shown in Figure 9 , Red lines indicate a strong abrupt citation over a year or several years (27). The burst intensity range of the 20 references was 17.68 to 40.35, and the endurance intensity was between 2 and 5 years. The contents of Table 5 are the main research contents of the top 20 citations Bursts of reference. The outbreak of the strongest citations (strength = 40.35) was titled “Mechanism of chemoresistance mediated by miR-140 in human osteosarcoma and colon cancer cells”, authored by Jones KB et al. with citation bursts from 2012 to 2017. The second ranked reference in the citation burst (strength = 34.73) was titled “Osteosarcoma treatment - where do we stand? A state of the art review”, published in Cancer Treatment Reviews by Luetke A et al. with citation bursts from 2016 to 2019.

Analyzing keyword co-occurrences is crucial for identifying research hotspots in a certain area. Table 6 shows the top 40 high-frequency keywords. Among these keywords, except for the subject words we searched, migration and invasion, apoptosis/proliferation, biomarker, chemoresistance, epithelial-mesenchymal transition and wnt/beta-catenin pathway appear more than 100 times, which represent the main hot research direction of ncRNAs in OS. Among the keywords related to ncRNAs, miRNA has the most keywords (n = 1,965), followed by lncRNA (n = 644) and circRNA (n = 255).

We use lines to connect nodes, the thicker the line, the closer the relationship, and the larger the node, the more frequency. As shown in Figure 10 , we analyze the information of keywords and obtain four clusters. For example, the keywords in the first clusters consists of angiogenesis “vegf”, “tumorigenesis”, “tumor microenvironment”, “tgf-beta signaling pathway”, “sirna, progression”, “p53”, “osteosarcoma”, “osteoblast”, “lung metastasis/lung cancer”, “immune”, “hif-1 alpha”, “gene target”, “exosome”, etc. From the distribution characteristics of keywords in the average publication year, the research on ncRNAs of OS is mainly concentrated in 2017-2020. Among them, the research on siRNAs were earlier, concentrated around 2017, the research on miRNAs were concentrated around 2018-2019, the research on lncRNAs were concentrated around 2019-2020, the research on circRNAs were later, concentrated in 2020. In addition, we also found that the research of “tumor microenvironment”, “immune”, “exosome”, “cerna” and “bioinformatics” in ncRNA is mainly concentrated in 2020 or later, indicating that they are the research hotspots and trends since 2020.

We compile the available literature by year and discover that there was zero material published between 2001 and 2007, proving that the current research on ncRNA in OS has not been conducted and that there is no scientific foundation for this topic. An average of 44 publications were published annually between 2008 and 2013, showing that this area of study is still in its early stages. From 2014 to 2023, the number of papers published began to increase significantly. In the past five years, the research publications on ncRNA in OS have exploded, indicating that more and more scholars have paid attention to this research.

Judging from the publications and cooperative relations of different countries, China is the main force in carrying out ncRNAs research on OS, followed by the United States. We have noticed that there are varying degrees of cooperation among China, United States, Germany, Canada, United Kingdom and Australia. In addition, the United States is actively cooperating with Israel, Chile, Canada and Italy. From the point of view of the research time and the average number of published literature, the research on ncRNAs in OS in the United States, Japan, Switzerland, United kingdom, Canada, Israel, Denmark Norway, et al. are relatively early, and the published research results are. mainly concentrated around 2016.The research results of China, Turkey, Iraq, Egypt, Iran, Poland, Mexico, Thailand, India, Malaysia, Pakistan, Saudi Arabia, Czech Republic, Brazil, et al. were mainly concentrated after 2018, which was carried out later.

In terms of the number of publications by research institutions, the top ten research institutions are all located in China. These institutions, including Shanghai Jiao Tong University, Tongji University and Fudan University have established cooperative relationships with each other. The Massachusetts General Hospital, Harvard University, Huazhong University of Science and Technology and Zhengzhou University also cooperate actively. However, we observed that while research institutions in China publish a large number of research papers, their collaboration with research institutions in other countries is limited. The lack of international cooperation may hinder the long-term development of academic research. While there has been some cooperation with certain countries, it has not been as extensive and close as hoped. Therefore, in order to jointly advance the development of ncRNA in OS, we advise research institutions from various nations to engage in broad collaboration and exchanges.

Since the majority of studies on ncRNA in OS were published in Oncology Letters (n = 139, Q3), it is clear that this journal is now the most well-liked in the field. Biomedicine & Pharmacotherapy had the largest impact factor (IF = 7.5, Q1), followed by Cancer Cell International (IF = 5.8, Q1). According to our analysis, more than half of the co-cited journals are high-impact Q1 journals. These are undoubtedly reputable, international journals that promote ncRNA research in OS. Additionally, very few studies on ncRNA in OS are currently published in journals that are clinically relevant, with the majority of the research being published in journals related to biology, molecular science, and pathology. This shows that the majority of the current research is still in the basic research stage.

The authors with the largest number of publications are Wei Wang (n = 33), Wei Liu (n = 32) and Zhenfeng Duan (n = 31). Wei Wang published 33 papers, two of which explored the molecular mechanism and pathogenesis of OS through integrated analysis of mRNA and miRNA microarrays and circular RNA 0001785 as a ceRNA to upregulate HOXB2 regulation by sponge miR-1200 (28, 29). Additionally, they discovered that osteoblastoma and OS can be distinguished by hypoxia-related microRNA-210, which is a diagnostic marker (30). Another important discovery is that CircDOCK1 can advance OS and control cisplatin sensitivity via the miR-339-3p/IGF1R axis (31). Therefore, a critical mechanism and potential therapeutic target for OS may be the circDOCK1/miR-339-3p/IGF1R axis. This discovery offers an additional molecular strategy to help the pathological characterization of two difficult-to-diagnose musculoskeletal cancers. 32 papers by Wei Liu were published. He demonstrated that miR-221-3p (32) and circular RNA PVT1 (circPVT1) (33) are anticipated to be new targets for OS treatment and that inhibition of miR-210-5p may represent a promising OS treatment (34) in addition to identifying the molecular mechanism of long non-coding RNA (lncRNA) PGM5-AS1 in EMT and OS progression (35). Zhenfeng Duan has published 31 related papers. He found that multidrug resistance in osteosarcoma is associated with downregulation of miR-15b, and miR-15b reconstruction can reverse chemotherapy resistance of OS (36). In addition, he also found that miR-199a-3p may play a functional role in OS cell growth and proliferation, and improving the function of miR-199a-3p may provide help for osteosarcoma treatment (37). His findings provide new insights for miRNA research in osteosarcoma. Wang Y (cited = 676) is the author with the most citations. In 2009, Wang Y proved that the expression of miR-140 was connected to the chemosensitivity of OS xenografts utilizing high-throughput miRNA expression analysis. By blocking HDAC4-mediated G1 and G2 phase arrest, MiR-140 inhibits cell growth and contributes to chemoresistance (38). For the development of novel treatment strategies to overcome drug resistance, MiR-140 may be a viable target. Both the molecular mechanism of miR-215 in chemoresistance in OS cells and the downregulation of microRNA-143 in OS, which promotes apoptosis and reduces tumorigenicity by targeting Bcl-2, were investigated by Wang Y in 2010 (39, 40). In OS cell lines, miR-133a was discovered to suppress cell growth, enhance apoptosis, and imply its potential for cancer treatment in 2013 (41). The same year, it was discovered that miR-103 and -107 govern DNA damage repair (42) and that miR-335 prevents OS cell migration by targeting the ROCK1 gene (43), revealing new participants in the progression of cancer and the response to chemotherapy. Wang Y made the discovery of the novel long non-coding RNA known as hypoxia-inducible factor 2 promoter upstream transcript in 2015. This RNA inhibits OS stem cells in vitro. TUG1 can be employed as a molecular marker to keep monitoring and forecast prognosis because it is connected with OS disease status and a poor prognosis (44).Wang Y provided evidence in 2016 that miR-29b suppresses tumor growth in OS by targeting CDK6 during proliferation and migration (45). Clearly, Wang Y’s accomplishments have established a theoretical and experimental basis for ncRNA study in OS.

When a reference is cited by multiple publications together, it is called a co-cited reference. Co-cited reference can be considered as the foundation for studying a particular topic (46). To determine the research foundation of ncRNA in OS, we chose 10 co-cited articles with the highest number of co-cited articles for this bibliometric analysis ( Table 5 ; Figure 8 ). Ottaviani G et al. published the most co-cited study in 2009, and the research provides methods, knowledge and explanation of the epidemiology of OS, and communicates the results to patients and their families (47). The second co-cited study is about real-time quantitative polymerase RCR and 2(-Delta Delta C(T)) Method of related gene expression published by Livak KJ et al. in 2001 (48). Up to now, PCR is still the main tool to study the role of ncRNAs in OS. The third co-cited study is a review published by Bartel DP in the journal Cell in 2004, which is the most influential among the 10 articles. According to their research, miRNAs are endogenous 22ntRNAs that target mRNA for cleavage or translation inhibition. MiRNAs are thought to have a significant regulatory role in both plants and mammals. Although miRNAs have just recently come to light, they are a diverse class of molecules that regulate gene expression in multicellular organisms and may have an impact on the production of several protein-coding genes (49). The findings of this study are crucial for understanding how miRNAs are controlled in OS. The fourth co-cited study, published by Mirabello I et al. in 2009, gave a detailed description of the incidence and survival of OS and compared age and ethnic groups. Their studies showed significant differences in morbidity, survival, pathological subtypes and anatomical sites among different age groups, and quantified the effects of OS as a secondary cancer on morbidity and mortality in patients with Paget disease (50). The biology and epidemiology of OS may be better understood as a result of these research. The fifth co-cited study was published by Isakoff MS et al. in 2015 regarding the current treatment and combination therapy for OS. They believe that high-dose methotrexate, doxorubicin and cisplatin (MAP) are the most effective treatments. The use of extra cytotoxic chemotherapeutic drugs like ifosfamide and the inclusion of biological therapies like cell wall tripeptide did not eventually increase the survival rate of patients with OS (51). It is undeniable that the survival rate of OS has significantly improved after the emergence of multi agent chemotherapy regimens. However, due to the fact that the research data at that time was nonrandom, there is still a lot of controversy about the ideal combination of chemotherapy drugs. The sixth co-cited study was published by Luetke A et al. in 2014. They reviewed the progress in the treatment of OS in terms of etiology, genetic instability, extensive histological heterogeneity, lack of biomarkers, local invasiveness and rapid metastatic potential of OS (52).Overall, the following subjects are covered by the top 6 references that were also cited: gene expression, regelation mechanism, survival rate and prognosis, biomarker, metastasis, treatment response, chemotherapy drugs and miRNA signatures, which are the key research of ncRNAs in OS.

References with citation bursts are widely cited and mentioned by other scholars, so these literatures suggest new problems in specific research fields (53). The biological function and pathogenicity of miRNA in OS, as well as how to employ miRNA to stop OS migration, are among the core research issues of ncRNA in OS research, as evidenced by the main research contents of the strong citation burst literature ( Table 5 ). They include miR-140, miR-21, mir-34a, etc. Keywords can aid us in swiftly capturing the distribution and development of ncRNA hotspots in OS research in addition to citing new literature. Table 6 includes the following keywords: apoptosis/proliferation, migration and invasion, prognosis, biomarker, chemoresistance, et al. As shown in Figure 10 , our analysis of trend topics and keyword clustering shows that the research of ncRNA in OS mainly focuses on the following aspects:

This study offers a number of distinctive benefits. First and foremost, for the first time, we employed bibliometrics to thoroughly examine the non-coding RNA research in OS, which can offer thorough guidance for academics that focus on related research. Secondly, our survey was done using three bibliometric tools, two of which are well-known in the bibliometrics community (VOSviewer and Cite Space), making it more likely that our data analysis was unbiased. Finally, bibliometric analysis offers cutting-edge insights and more thorough hot spots than conventional reviews.

Of course, there are some weaknesses in this study as well. First of all, this study only used data from the Wo SCC database, neglecting data from other databases, which means it might have missed some related research. Second, we reviewed studies that were written in English, which may indicate that non-English writing samples are undervalued.