Visualization analysis of research hotspots and trends on gastrointestinal tumor organoids

Abstract

BACKGROUND

Gastrointestinal tumor organoids serve as an effective model for simulating cancer in vitro and have been applied in basic biology and preclinical research. Despite over a decade of development and increasing research achievements in this field, a systematic and comprehensive analysis of the research hotspots and future trends is lacking.

AIM

To address this problem by employing bibliometric tools to explore the publication years, countries/regions, institutions, journals, authors, keywords, and references in this field.

METHODS

The literature was collected from Web of Science databases. CiteSpace-6.2R4, a widely used bibliometric analysis software package, was used for institutional analysis and reference burst analysis. VOSviewer 1.6.19 was used for journal co-citation analysis, author co-authorship and co-citation analysis. The ‘online platform for bibliometric analysis (https://bibliometric.com/app)’ was used to assess the total number of publications and the cooperation relationships between countries. Finally, we employed the bibliometric R software package (version R.4.3.1) in R-studio, for a comprehensive scientific analysis of the literature.

RESULTS

Our analysis included a total of 1466 publications, revealing a significant yearly increase in articles on the study of gastrointestinal tumor organoids. The United States (n = 393) and Helmholtz Association (n = 93) have emerged as the leading countries and institutions, respectively, in this field, with Hans Clevers and Toshiro Sato being the most contributing authors. The most influential journal in this field is Gastroenterology. The most impactful reference is "Long term expansion of epithelial organs from human colon, adenoma, adenocarcinoma, and Barrett's epithelium". Keywords analysis and citation burst analysis indicate that precision medicine, disease modeling, drug development and screening, and regenerative medicine are the most cutting-edge directions. These focal points were further detailed based on the literature.

CONCLUSION

This bibliometric study offers an objective and quantitative analysis of the research in this field, which can be considered as an important guide for next scientific research.

Key Words: Gastrointestinal tumor organoids; Bibliometric analysis; Drug development and screening; Model; CiteSpace

Core Tip: Bibliometrics was used to quantitatively analyze 1466 articles from Web of Science databases. Our manuscript provided a systematic and comprehensive analysis of the research trends and hotspots in this field, identified the most productive countries or regions, and highlighted the most influential journals, authors and references. We also offered a comprehensive and in-depth understanding of the research trends and hotspots in the field of gastrointestinal tumor organoids and discussed their future applications. This information will be beneficial for the future construction and application of gastrointestinal tumor organoids.

INTRODUCTION

Gastrointestinal cancers (GIcs) encompass a range of cancers that occur in gastrointestinal tissue, including esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), biliary cancer and pancreatic cancer (PC)[1]. Despite its prevalence, effective early diagnostic methods for GIcs are lacking. Conventional treatment methods are limited to traditional surgical resection, radiotherapy, and drug therapy, which includes chemotherapy, targeted therapy, and immunotherapy[2]. Consequently, GIcs have a high incidence rate and mortality. Therefore, it is urgent to explore new research methods for GIcs. The development and utilization of preclinical trial models have significantly contributed to gastrointestinal cancer research. Traditional cancer models, such as various genetically engineered mouse models, patient-derived tumor xenografts and two-dimensional (2D) culture models based on cancer cell lines, have been invaluable in scientific research[3]. However, these models also have notable limitations. For instance, genetically engineered mouse models are unsuitable for high-throughput sequencing and drug screening[4], while tumor xenografts studies involve lengthy research cycles and high costs. The advent of organoid models has effectively addressed these shortcomings, garnering an increasing amount of attention from the scientific and medical communities[5].

Organoids are 3D cultures derived from tissues, typically originating from multifunctional stem cells, embryonic stem cells, or adult stem cells[6]. They can mimic the function, morphological structure, and biological activity of original tissues and organs, making them useful for disease research and drug screening[7]. Since 2009, there has been a dedicated focus on organoids. Nowadays, cancer organoid models have been successfully established in various types of cancer, including gastrointestinal cancer[8], breast cancer[9], lung cancer[10] and prostatic cancer[11]. Compared to 2D models, organoids offer advantages in modeling organogenesis, modeling human development and disease due to their ability to better match with the native organs[12]. In recent years, an increasing number of preclinical trials choose patient-derived organoids as a new generation of in vitro models. Organoids derived from cancer patients largely retain the original mutation, genetic phenotypic, and behavioral characteristics of tumors, and have been extensively utilized in medical research, disease modeling, and drug sensitivity experiments[13,14]. For example, patient-derived CRC organoids can accurately simulate the proliferation, differentiation, diffusion, and metastasis of CRC, and can predict the response of rectal cancer patients to drugs with high accuracy[15]; organoids derived from biliary tract cancer and PC retain the heterogeneity, gene expression profile and genetic characteristics of the original tumor, which can be used to study epigenetic therapy, drug development and pathological research[16]. Therefore, it is worthwhile to further explore organoids derive from gastrointestinal tumors in the future, and we believe that scientific methods can be explored to cure this type of cancer.

In the past decade, significant advancements have been made in the research of gastrointestinal cancer organoids. However, there is a noticeable gap in the bibliometric analysis in this field. Bibliometric analysis involves quantitatively analyzing all knowledge within a specific field using bibliometric tools. This method is now widely employed in social sciences[17], big data and artificial intelligence[18], biomedical research[19]. Researchers can discover frontier science from a large number of articles, explore research hotspots, and better understand research content, popular journals, and cooperation network graphs between countries using bibliometrics[20]. This study aims to provide a comprehensive and in-depth understanding of the research trends and hotspots of gastrointestinal tumor organoids by conducting both quantitative and qualitative analyses of the relevant literature. The findings of this study will serve as a valuable reference for researchers worldwide.

MATERIALS AND METHODS

Data collection

The data for this analysis were sourced from the Web of Science Core Collection (WoSCC), a repository renowned for its high-quality articles and frequently utilized for bibliometric research[21]. The search criteria included “articles” and “review articles” published in English, for which the retrieval date was July 4, 2023. Initially, 1675 articles were retrieved, but those unrelated to gastrointestinal cancer organoids were subsequently excluded. The final sample comprised 1466 publications. Complete records and cited references of these publications were downloaded from the WoSCC database in plain text files format and tab separator format, and then subjected to analysis via bibliometric tools.

Retrieval strategy

(TS = (”gastrointestinal cancer*” OR “gastrointestinal neoplas*” OR “gastrointestinal tumor*” OR “gastrointestinal carcinoma*” OR “gastrointestinal malignanc*” OR “digestive cancer*” OR “digestive neoplas*” OR “digestive tumor*” OR “digestive carcinoma*” OR “digestive malignanc*” OR “gastric cancer*” OR “gastric neoplas*” OR “gastric tumor*” OR “gastric carcinoma*” OR “gastric malignanc*” OR “stomach neoplas*” OR “stomach cancer*” OR “stomach tumor*” OR “stomach carcinoma*” OR “stomach malignanc*” OR ”biliary cancer*” OR “biliary neoplas*” OR “biliary tumor*” OR “biliary carcinoma*” OR “biliary malignanc*” OR “biliary tract cancer*” OR “biliary tract tumor*” OR “biliary tract neoplas*” OR “biliary tract carcinoma *” OR “biliary tract malignanc*” OR “esophageal cancer*” OR “cholangiocarcinoma*” OR “esophageal neoplas*” OR “esophageal tumor*” OR “esophageal carcinoma*” OR “esophageal malignanc*” OR “pancreatic cancer*” OR “pancreatic neoplas*” OR “pancreatic tumor*” OR “pancreatic carcinoma*” OR “pancreatic malignanc*”OR “intestinal cancer*” OR “intestinal neoplas*” OR “intestinal tumor*” OR “intestinal carcinoma*” OR “intestinal malignanc*” OR “colorectal cancer*” OR “colorectal neoplas*” OR ”colorectal tumor*” OR “colorectal carcinoma*” OR “colorectal malignanc*” OR “colon cancer*” OR “colon neoplas*” OR “colon tumor*” OR “colon carcinoma*” OR “colon malignanc*” OR “rectal cancer*” OR ”rectal neoplas*” OR “rectal tumor*” OR “rectal carcinoma*” OR “rectal malignanc*” OR “anal cancer*” OR “anal tumor*” OR “anal neoplas*” OR “anal carcinoma*” OR “anal malignanc*” OR “pancreatic adenocarcinoma*” OR ” stomach adenocarcinoma*” OR “colon adenocarcinoma*” OR “rectum adenocarcinoma*”) AND TS = (“organoid*”)).

Data analysis and visualization

CiteSpace-6.2R4, a widely used bibliometric analysis software package, was used for institutional analysis and reference burst analysis. This software, based on the JAVA environment, visualizes scientific literature and constructs association network graphs[22].

VOSviewer 1.6.19 was used for journal co-citation analysis, author co-authorship and co-citation analysis. This software uses a co-occurrence matrix to calculate a similarity matrix, which is subsequently used to construct and view a large number of data literature visualization images[23]. It offers four image forms, label view, density view, cluster density view and scatter view, and can easily process visualization images of thousands of projects[23]. Moreover, the journal partition is based on the Journal Citation Reports (JCR) partition in 2022. The Impact Index Per Article sourced from the Reference Citation Analysis database (https://www.referencecitationanalysis.com/).

We utilized the ‘online platform for bibliometric analysis (https://bibliometric.com/app)’ to assess the total number of publications and the cooperation relationships between countries. Column charts were created using Microsoft Excel.

Subsequently, we employed the bibliometric R software package (version R.4.3.1) in R-studio, for a comprehensive scientific analysis of the literature. This package, based on the R programming language, facilitates the analysis of co- citations, co- words, co-authors, and other aspects. The results are presented in intuitive images or tables for effective data visualization[24]. The bibliometric R software package was used for keyword analysis.

RESULTS

Global publication trends

To elucidate the growth rate of research on gastrointestinal tumor organoids, we analyzed the total number of publications worldwide on this topic. Prior to 2014, research on gastrointestinal cancer organoids was in its nascent stages. However, from 2014 to 2022, there was a rapid surge in global publications and 159 publications can be available as of July 2023 (Figure 1). The trend line indicates that the number of articles published in 2023 will surpass that published in 2022. The rapid growth rate is likely attributable to the increasing recognition of gastrointestinal tumor organoids as a vital tool for basic and clinical tumor research. It is anticipated that this topic will continue to be a prominent area of research for a considerable period in the future.

Figure 1 Trends in global publications in the field of gastrointestinal tumor organoids.

Country/region analysis

In the field of gastrointestinal tumor organoids, a total of 58 countries/regions have published articles. The United States leads in this field with the highest number of publications (n = 393), accounting for approximately 26.8% of the total publications. These countries were followed by China (n = 249), Germany (n = 146), and Japan (n = 146), which accounted for 16.98%, 10%, and 10% of the total publications, respectively (Figure 2A). Additionally, we generated a trend chart depicting the top five countries with the highest number of published articles over the past five years (Figure 2B). From 2018 to 2022, the United States demonstrated an upward trend in the total number of articles published in the field of gastrointestinal tumors, peaking in 2020 with 74 publications. Concurrently, the number of articles published in China, Germany, and Japan escalated at various rates, with China exhibiting the most significant growth rate, surging from 10 publications in 2018 to 95 publications in 2022. To further illustrate the research landscape of gastrointestinal cancer organoids across different countries, we employed a bibliometric online platform to analyze the collaborative relationships among various countries. The lines linking two countries signify a collaborative relationship. The United States emerged as the country with the highest frequency of international cooperation in this field, maintaining close collaborative ties with countries such as China, Germany, and the Netherlands (Figure 2C).

Figure 2 Countries/regions contributing to gastrointestinal tumor organoid research. A: Top ten countries with the highest number of publications research on gastrointestinal tumor organoids; B: Trend chart of publications in the top five countries with the highest number of published articles over the past five years; C: Collaborative diagram between different countries in the field of gastrointestinal tumor organoids.

Institutional analysis

To visualize the distribution of research institutions, we utilized CiteSpace to generate a network visualization image of institutional collaboration Figure 3. According to Table 1 and Figure 3, in the field of research on gastrointestinal tumor organoids, the top five influential institutions are the Helmholtz Association (n = 93) and the German Cancer Research Center (DKFZ) (n = 75) from Germany, Utrecht University (n = 85), Utrecht University Medical Center (n = 81) and Hubrecht Institute (KNAW) (n = 67) from the Netherlands. While most institutions maintain collaborative relationships, among the top ten institutions, Sun Yat-sen University in China and the University of California System in the United States exhibit a high centrality. These findings suggest that these two institutions possess robust research capabilities in the field of gastrointestinal tumor organoids and exert a significant global influence.

Figure 3 Visualization of the relationship between institutions in the field of gastrointestinal tumor organoids. The nodes in the figure represent different institutions, and the size of the nodes represents the number of research achievements of the institutions. Different colors represent different years, and the lines between the circles represent cooperative relationships between institutions.

Table 1 Statistics of the top 10 most prolific institutions in the study of gastrointestinal tumor organoids.

Rank	Affiliations	Country	Centrality	Publications
1	Helmholtz Association	Germany	0.04	93
2	Utrecht University	Netherlands	0.03	85
3	Utrecht University Medical Center	Netherlands	0.03	81
4	German Cancer Research Center (DKFZ)	Germany	0.02	75
5	Hubrecht Institute (KNAW)	Netherlands	0.07	67
6	Royal Netherlands Academy of Arts & Sciences	Netherlands	0.06	66
7	Harvard University	United States	0.01	53
8	University of California System	United States	0.13	49
9	UDICE-French Research Universities	France	0.04	43
10	Sun Yat-sen University	China	0.11	40

Journal analysis

Our analysis of journals revealed that a total of 393 journals published articles pertaining to gastrointestinal tumor organoids. Table 2 lists the top 10 journals with the most publications. The journal of Cancer led with 83 articles, constituting approximately 5.66% of the total number of publications. This was followed by Gastroenterology with 51 articles, representing approximately 3.5% of the total number of publications. Gastroenterology also had the highest H-index with a value of 28. Furthermore, all the top 10 journals fall within Zone 1 and Zone 2, and the JCR zoning results highlight the crucial role these top 10 journals play in this field. We used VOSviewer to generate a visual representation of the journal co-citation network (Figure 4). This contributes to identifying core journals in the field of gastrointestinal tumor organoids and assessing their level of specialization[25]. The larger circles of representing Nature, Cancer and Cell denote a high number of citations. Nature had the most citations (n = 5009), followed by Cell (n = 4009) and Proceedings of the National Academy of Sciences of the United States of America (n = 2435; Table 2). The connections between Nature and other journals such as Cell and Cancer Cell suggest frequent citations and close relationships. The co-citation journal analysis further indicated that research on gastrointestinal tumor organoids significantly influences journals, such as Nature, Cancer, Cell and Clinical Cancer.

Figure 4 Visualization images of the journal co-citation network in the field of gastrointestinal tumor organoids. Each node represents a journal, while larger nodes represent more co-citations. The lines between nodes represent co-citation relationships, while thicker lines indicate more co-citation relationships. Different colors represent different clusters.

Table 2 Statistics on the number of publications and total citations from the top ten journals in the field of gastrointestinal tumor organoids.

Rank	Sources	Articles	Zone	H-index	Cited sources	Citations
1	Cancers	83	Q2	18	Nature	5009
2	Gastroenterology	51	Q1	28	Cell	4009
3	Oncogene	40	Q1	17	Proceedings of the National Academy of Sciences of the United States of America	2435
4	Cancer Research	37	Q1	19	Gastroenterology	2399
5	Scientific Reports	36	Q2	15	Cancer Research	2340
6	Nature Communications	35	Q1	16	Science	2225
7	Frontiers in Oncology	33	Q2	9	Nature Medicine	1969
8	Cellular and Molecular Gastroenterology and Hepatology	24	Q1	12	Cell Stem Cell	1807
9	Journal of Experimental & Clinical Cancer Research	23	Q1	12	Nature Communications	1507
10	Cancer Science	21	Q2	7	Clinical Cancer Research	1490

Co-authorship and co-citation analysis of influential authors

A visual analysis of collaboration among the top 385 authors was conducted (Figure 5A), along with a co-citation analysis of the top 380 authors (Figure 5B). Table 3 lists the top 10 authors based on the number of publications. Hans Clevers leads with 51 articles, followed by Toshiro Sato (n = 20), David Tuveson (n = 15), Onno Kranenburg (n = 15) and Masanobu Oshima (n = 15). The links between the nodes suggest a close cooperative relationship among multiple authors. However, Jun Yu, Yeguang Chen and Jihui Hao appear to have limited collaboration with other authors. As shown in Figure 5B and Table 3, the top five authors with the highest number of co-citations are Toshiro Sato (n = 1014), Nick Barker (n = 467), Marc van der Wetering (n = 410), Jarnor Drost (387 times) and Sylvia F Boj (n = 320). The connections between these authors indicate a close co-citation relationship.

Figure 5 Co-authorship and co-citation analysis of influential authors. A: A collaborative network view among authors in the field of gastrointestinal tumor organoid research. Each node represents an author, and the size of the node represents the number of publications. The connection between the two nodes indicates a cooperative relationship; B: Visualization of co-citation authors in the field of gastrointestinal tumor organoids. The size of the nodes is proportional to the total number of citations. The connection between two nodes represents a co-citation relationship, and different colors represent different clusters.

Table 3 Statistics on the number of publications and citations of top 10 authors in the field of gastrointestinal tumor organoids.

Rank	Authors	Documents	Cited author	Citations
1	Hans Clevers	51	Toshiro Sato	1014
2	Toshiro Sato	20	Nick Barker	467
3	David Tuveson	15	Marc van der Wetering	410
4	Onno Kranenburg	15	Jarno Drost	387
5	Masanobu Oshima	15	Sylvia F Boj	320
6	Owen J Sansom	14	Masayuki Fujii	307
7	Van der Laan	14	Meritxell Huch	289
8	Monique Verstegen	13	Georgios Vlachogiannis	262
9	Deniel Stange	13	Herve Tiriac	226
10	Emile Voest	13	Rebecca L Siegel	226

Keyword analysis

To better understand the key topics and future trends in gastrointestinal tumor organoid research, we used the R-bibliometric software package to list the top 50 keywords automatically (Figure 6A). We found that the top five keywords in the ranking were “expression” (n = 296, 7%), "stem-cells” (n = 272, 6%), “in-vitro” (n = 227, 5%), “colorectal-cancer” (n = 193, 5%) and “cancer” (n = 156, 4%). Moreover, we built a map to reflect the co-occurrence relationships between keywords (Figure 6B). There was a strong co-occurrence relationship between “expression”, “in-vitro”, “colorectal-cancer” and “stem-cells”. These keywords not only are central to the study of gastrointestinal tumor organoids but also reflect the research direction in this field.

Figure 6 Analysis of keywords. A: Tree map of keywords in the study of gastrointestinal tumor organoids; B: The keywords co-occurrence network in the field of gastrointestinal tumor organoids; C: A map of trend topic in the field of gastrointestinal tumor organoids between 2012 and 2023. The size of the circle is positively correlated with its frequency of occurrence.

To better understand the significant trends in this field, we conducted a trend topic analysis. As shown in Figure 6C and Table 4, in 2020, the keywords “expression”, “stem cells”, and “in vivo” had the highest frequency of occurrence, indicating that they were the primary research focus areas over the past five years. Prior to 2018, keywords such as "organic culture”, “wnt receptors”, and “bacterial pancreatic cancer" had already appeared in research on gastrointestinal tumor organoids, indicating that the generation of these organoids had long been a focus of attention. The frequent appearance of the keywords “lgr5” and “epithelium”, in 2018 indicated that the research topic at that time was the construction of gastrointestinal tumor organoids. The emergence of high-frequency keywords in recent years, such as "patient-driven organizations", indicates research hotspots and trends. We hypothesize that after 2023, research on gastrointestinal tumor organoids may lean towards "patient-derived organs”, “metabolisms”, “cultures” and “pharmacokinetics".

Table 4 Trending topic in the field of gastrointestinal tumor organoids between 2012 and 2022.

Item	Frequency	Year_q1	Year_med	Year_q3
Negative regulator	7	2012	2014	2020
Organotypic culture	6	2016	2016	2019
Wnt receptors	6	2015	2016	2018
Ductal pancreatic-cancer	8	2017	2017	2018
Paneth cells	6	2015	2017	2020
Adenomas	5	2017	2017	2021
Lgr5	22	2016	2018	2019
Crypt	20	2017	2018	2020
Epithelium	19	2016	2018	2019
In-vitro expansion	69	2018	2019	2021
Beta-catenin	58	2017	2019	2021
Tumorigenesis	51	2017	2019	2021
Expression	296	2019	2020	2022
Stem-cells	272	2019	2020	2022
In-vitro	227	2018	2020	2022
Cancer	156	2019	2021	2022
Cells	148	2019	2021	2022
Activation	132	2019	2021	2022
Patient-derived organoids	31	2021	2022	2022
Metabolism	28	2018	2022	2022

Reference citation and burst analysis

By analyzing the citation frequency of references, we can identify the core journals in the field of gastrointestinal tumor organoids[26]. We analyzed the top 10 most frequently cited references related to the research on gastrointestinal tumor organoids, which were published between 2007 and 2018 (Figure 7A). Among these, four local citations exceeded 300. The title with the highest number of local citations is “Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium”, with 451 Local citations[27]. The second most locally cited paper was published by Sato et al[27] in Nature, and was entitled "Single Lgr5 stem cells build crypt villus structures in vitro without a metallic niche", with 389 Local citations. The third most cited paper is “Prospective derivation of a living organoid biobank of colorectal cancer patients”, with 374 local citations.

Figure 7 Analysis of reference citation and burst. A: Top ten references with the highest number of local citations in the field of gastrointestinal tumor organoids; B: The top forty references with the most citation bursts.

Articles with explosive citations indicate a high citation rate over a specific period[28]. We analyzed 40 references with the most significant citation bursts. Figure 7B illustrates this phenomenon, with a red rectangle indicating a surge in literature citations during that year and a blue matrix indicating the time interval of citation bursts. Table 5 presents the top 10 articles with the strongest citation bursts. The paper with the most substantial citation burst was "Prospective derivation of a living organoid biobank of colorectal cancer patients" published in Cell in 2015, with a burst strength of 46.9 and an impact index of 183.5. This paper garnered significant attention from researchers from 2016 to 2020. The paper ranked second in burst intensity is "Organoid Models of Human and Mouse Dual Pancreatic Cancer", also published in Cell, with a burst intensity of 34.04 and an impact index of 132.1. The third most explosively cited paper is "Long term Expansion of Epithelial Organoids from Human Colon, Adenoma, Adenocarcinoma, and Barrett's Epithelium", published in Gastroenterology, this paper received considerable attention from 2013 to 2016, with a burst intensity of 31.15 and an impact index of 179.2. Among the 10 references with the strongest burst intensity, three were published in Cell, two were published in Nature.

Table 5 Top ten articles with the strongest citation bursts.

Strength	Tittle	Source	First author	Impact index per article1
46.9	Prospective derivation of a living organoid biobank of colorectal cancer patients	Cell	Marc van de Wetering	183.5
34.04	Organoid models of human and mouse ductal pancreatic cancer	Cell	Sylvia F Boj	132.1
31.15	Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium	Gastroenterology	Toshiro Sato	179.2
21.96	Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids	Nature Medicine	Mami Matano	81.2
20.92	Sequential cancer mutations in cultured human intestinal stem cells	Nature	Jarno Drost	76.6
17	Deterministic progenitor behavior and unitary production of neurons in the neocortex	Cell	Peng Gao	30.7
16.73	Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients	Cell Stem Cell	Gerald Schwank	89.8
16.27	Comprehensive molecular characterization of human colon and rectal cancer	Nature	Cancer Genome Atlas Network	507.3
16.04	Oncogenic transformation of diverse gastrointestinal tissues in primary organoid culture	Nature medicine	Xingnan Li	29.5
16.02	Preserved genetic diversity in organoids cultured from biopsies of human colorectal cancer metastases	Proceedings of the National Academy of Sciences of the United States of America	Fleur Weeber	31.1

¹The impact index per article is presented based on Reference Citation Analysis.

DISCUSSION

Through a bibliometric analysis of global research on gastrointestinal tumor organoids, we can gain a comprehensive understanding of the knowledge shifts and developmental trends in this area[29]. The past decade has witnessed a significant surge in research in this domain, indicating a likelihood of further relevant research in the future.

According to the results of the analysis, the United States and China have emerged as leaders in the publication on gastrointestinal cancer organoids. Furthermore, the Helmholtz Association is the institution with the most published literature and maintains close cooperative relationships with other institutions. These findings suggest that the close cooperation between countries or institutions will help promote the development of gastrointestinal tumor organoids in the future.

Hans Clevers and Toshiro Sato have proven to be leading contributors to the field of gastrointestinal organoids research. Hans Clevers has published the largest number of papers and is one of the world's leading researchers in the role of adult stem cells in cancer and regenerative medicine research, while Sato has produced literature that extensively influences this field. As evident from the current analysis, the most cited paper was published by Sato et al[27]. In this study, the authors developed a long-term culture technique for primary epithelial cells isolated from the human small intestine and colon that was also suitable for the growth of human CRC cells[27]. This culture technology has had a profound impact on gastrointestinal cancer organoids.

The insights gleaned from keyword co-occurrence analysis, trending topic analysis, and citation burst analysis are invaluable for further exploration. These analyses reveal that the current research hotspots in gastrointestinal tumor organoids primarily revolve around precision medicine, disease modeling, drug development and screening, and regenerative medicine.

Precision medicine represents a novel biological approach that leverages next-generation sequencing technology to analyze the genetic sequences of cancer patients and tailor specific drugs for treatment[30]. The advancement of precision medicine is being propelled by genomics, proteomics, bioinformatics and big data[31]. However, the evolution of precision medicine necessitates in vitro models for predicting cancer treatments. Patient-derived tumor organoids, which closely mimic the original tumor tissue, offer an excellent platform for precision medicine[32]. Studies based on cancer organoids have demonstrated significant potential in predicting cancer treatment outcomes, suggesting that these organoids could serve as a powerful tool for translational research[33]. Therefore, precision medicine is poised to significantly advance research on gastrointestinal cancer organoids, particularly in the realm of high-throughput drug screening. Moreover, regenerative medicine is a scientific field that employs stem cells, biochemical factors, and other raw materials to create tissue substitutes in vitro[34]. These substitutes can be utilized for disease diagnosis and research[35]. The successful creation of gastrointestinal cancer organoids represents a significant scientific achievement in regenerative medicine. Various regenerative medicine strategies, including cell therapy, tissue engineering and gene therapy, can contribute to the development of cancer models[36]. At present, regenerative medicine based on gastrointestinal cancer organoids has been widely applied in GIcs, such as CRC, GC, and pancreatic cancer. However, regenerative medicine for cancer treatment still faces some challenges, including treatment durability and high cost[36]. This topic is worth continuing to explore in the future.

At present, existing gastrointestinal tumor organoid models require further optimization to facilitate more comprehensive preclinical trials. A complex organoid culture system has been developed to simulate the tumor microenvironment by incorporating exogenous immune cells, fibroblasts, and other components into the tumor organoid models[37]. This type of training system is a new strategy for developing personalized treatment. Moreover, the integration of organoids with organ-on-a-chip models is gaining popularity. These models involve the use of microfluidic devices, which are fabricated using microfluidic chips to emulate the functions of human tissues and organs[38]. Research on cancer using organ-on-a-chip technology based on microfluidics has shown that this technology not only improves the stability of organoids but also highly simulates the tumor microenvironment. This provides an exceptional platform for personalized drug screening and prognosis prediction[39]. In summary, the next generation of gastrointestinal tumor organoid models will be complex and diverse.

Finally, traditional 2D models have a high failure rate and significant time costs associated with cancer drug development and screening. In contrast, 3D tumor models maintain the characteristics of the original tissue, making them more suitable for drug development and screening[40]. Given the heterogeneity of gastrointestinal tumors, tumors from different sources may exhibit various responses to the same drugs. This necessitates the use of a large number of tumor organoid models for drug testing and screening. Since the successful construction of cancer organoids, numerous researchers have focused on building biobanks of cancer organoid, with the objective of conducting drug testing without requiring patient participation in the experiment[15]. Several gastrointestinal tumor organoid biobanks have been established for drug development and screening. For example, a high-risk colorectal adenoma organoid biobank was used for high-throughput drug screening[41], and a GC organoid biobank was employed to test and determine the sensitivity of certain drugs[42]. These biobanks not only provide abundant preclinical models for scientific research but also concentrate on testing specific potential drugs[43]. In the future, drug development and screening for gastrointestinal cancer based on tumor organoid biobanks will likely become a research trend.

Limitations

This research employs the latest bibliometric tools to provide an extensive analysis of gastrointestinal tumor organoids. To the best of our knowledge, this is the first investigation to employ bibliometric analysis of gastrointestinal tumor organoids. Although comprehensive, this study has several limitations. The data source for this study was solely the WoSCC database, and the analysis was restricted to papers and reviews, potentially leading to incomplete data. Furthermore, the study is limited to English language publications which may introduce certain biases or errors in the results.

CONCLUSION

Our results show that gastrointestinal tumor organoids research is becoming increasingly popular worldwide. The United States and China are leading in global research on gastrointestinal tumor organoids. Helmholtz Association and the University of California System are the most influential organizations based on their publications. The most influential journal in this field is Gastroenterology. Notably, Hans Clevers from Utrecht University in the Netherlands and Sato Toshiro from Japan have made outstanding contributions to this field. Our findings suggest that precision medicine, disease modeling, drug development and screening, and regenerative medicine, will be the next big topics in this field. This bibliometric study offers an objective and quantitative analysis of the research in this field, which can be considered as an important guide for future scientific research. In short, this bibliometric study provides an in-depth understanding of the trends and hotspots in gastrointestinal tumor organoids research. Our research findings will assist researchers in understanding the research status and planning future research directions.