Advances and global trends of precancerous lesions of gastric cancer: A bibliometric analysis

Abstract

BACKGROUND

Precancerous lesions of gastric cancer (PLGC) represent a critical pathological stage in the development of intestinal gastric cancer. Early detection and diagnosis are key to reducing the incidence of gastric cancer. Substantial advancements have been made in PLGC research in recent years, making it necessary to provide updated reviews using bibliometric methods. We hypothesize that this review will identify emerging trends, key research areas, and gaps in PLGC research, providing insights that could guide future studies and enhance prevention strategies.

AIM

To comprehensively review the current state of research on PLGC, examining development trends and research hotspots.

METHODS

We conducted a bibliometric analysis of PLGC-related studies published between 2004 and 2023 using the Web of Science Core Collection database. We employed Software, including VOSviewer, CiteSpace, R software, and SCImago Graphica, to map scientific networks and visualize knowledge trends in terms of publication volume, countries/regions, institutions, journals, authors, and keywords.

RESULTS

A total of 4097 articles were included, and overall publication volume showed an increasing trend. Over the past two decades, China published the most articles, followed by the United States, Japan, South Korea, and Italy. Among the top 10 contributors, the United States ranked highest in institutions, authors, and citations and demonstrated the strongest international collaboration. Research keywords in this field were clustered into three main categories: Risk factors, pathogenesis, and diagnosis and treatment. Pathogenesis and molecular biomarkers remain key areas of focus. Future research should explore the mechanisms of gut microbiota, immune microenvironment, metabolic reprogramming, and epigenetics. Advanced technologies, including single-cell sequencing, spatially resolved analysis, multi-omics approaches, artificial intelligence, and machine learning, will likely accelerate in-depth investigations of PLGC.

CONCLUSION

PLGC research has rapidly developed in recent years, gaining considerable attention. This bibliometric analysis reveals research state and emerging trends over the past 20 years, providing insights for future studies.

Key Words: Precancerous lesions of gastric cancer; Gastric precancerous lesion; Dysplasia; Bibliometric; Visualization

Core Tip: As a “golden turning point” in the development of intestinal-type gastric cancer, the early detection and treatment of precancerous lesions of gastric cancer can reduce the incidence of gastric cancer. This article provides a current review of precancerous lesions of gastric cancer research through bibliometric methods, helping researchers stay informed about the state of research and recent advancements in this field, while offering new ideas and directions for future studies.

INTRODUCTION

Gastric cancer is one of the most common malignancies of the digestive system, ranking fifth globally in terms of both incidence and mortality[1]. It has the highest incidence in East Asia and Eastern Europe and is the third leading cause of cancer-related deaths in China[1,2], imposing a substantial public health burden[3]. Recent studies have indicated that although the overall incidence of gastric cancer is expected to continue to decrease in most countries, the number of new cases is projected to increase, particularly among younger individuals[4], highlighting that gastric cancer remains a major global public health challenge.

Precancerous lesions of gastric cancer (PLGC) are pathological changes that predispose tissues to gastric cancer. In 1992, Correa et al[5] proposed a cascade model for the progression of intestinal-type gastric cancer, which has been widely accepted by the academic community. The development of intestinal-type gastric cancer follows the sequence of inflammation, atrophy, intestinal metaplasia, dysplasia/intraepithelial neoplasia, and gastric cancer, known as the Correa cascade[5]. In 2012, the European guidelines on the management of precancerous conditions and lesions in the stomach (MAPS) defined chronic atrophic gastritis and intestinal metaplasia as precancerous conditions, with dysplasia being the most direct precursor of gastric cancer[6]. Dysplasia/intraepithelial neoplasia is characterized by neoplastic epithelial proliferation with cytological and architectural atypia, but without convincing evidence of invasion[6]. In 2019, the World Health Organization (WHO) stated that dysplasia is more appropriately classified for tubular adenocarcinoma, and the 2019 updated European guidelines categorize dysplasia into low-grade and high-grade[7], which has gradually gained recognition and attention from researchers. Studies have shown that approximately 25% of patients with high-grade dysplasia in a cohort of PLGC patients were diagnosed with gastric cancer after one year of follow-up. Therefore, effective prevention and treatment of PLGC is a crucial strategy to halt the progression toward gastric cancer.

However, preventing the transition from PLGC to gastric cancer remains challenging. The pathogenesis of PLGC is not yet fully elucidated. Diagnosis primarily relies on gastric mucosal biopsies, with the number, depth, and size of biopsy specimens being critical factors for accurate diagnosis and assessment. In terms of treatment, Helicobacter pylori (H. pylori) eradication can delay or block PLGC progression and prevent gastric cancer[8].However, the therapeutic effects of folate supplementation, antioxidants, and vitamins on PLGC remain inconclusive, with varying results across different studies[9,10]. For patients with endoscopically defined PLGC, options such as endoscopic mucosal resection, endoscopic submucosal dissection, or surgical resection may be considered, along with high-quality endoscopic follow-up to monitor patient prognosis. In recent years, increasing attention has been directed toward the immune microenvironment[11,12], metabolic reprogramming[13], and gut microbiota[14,15], although these areas remain under active investigation. Therefore, a systematic review of previous research on PLGC is warranted to guide future studies.

Bibliometrics refers to the quantitative study of physical or bibliographic units or their substitutes using mathematical and statistical methods[16]. By analyzing various data points in published literature, including authorship, country of origin, affiliated institutions, journal publications, and keywords, bibliometrics can rapidly and accurately reveal research output, key topics, and future trends in a given field[17]. Bibliometrics has been widely applied across various fields of scientific research. Over the past two decades, numerous countries have conducted extensive studies on the pathogenesis, diagnostic criteria, treatment, and prognosis of PLGC. However, no bibliometric analysis has yet been performed specifically on PLGC. Therefore, this study employed bibliometric methods to summarize the current state of research on PLGC, uncover research hotspots, and predict future trends, aiming to provide reference points for in-depth studies and novel drug development in the field of PLGC.

MATERIALS AND METHODS

Data sources and search strategies

The data for this study were sourced from the Web of Science Core Collection (WoSCC) database. The search formula used was: (TS = (gastric OR stomach) AND TS = (dysplasia OR atypical hyperplasia OR intraepithelial neoplasia OR preinvasive cancer OR preinvasive lesion* OR preinvasive condition* OR precancerous lesion* OR precancerous condition* OR premalignant lesion* OR premalignant condition* OR premalignancy OR incipient neoplasia)) OR (TS = (“gastric premalignant condition*” OR “gastric premalignant lesion*” OR “precancerous lesions of gastric cancer” OR “gastric precancerous lesion*” OR “gastric precancerous condition*” OR “gastric precursor lesion*”)). The search period covered publications from 2004 to 2023, and only articles and reviews written in English were included. The search was conducted on September 17, 2024, and full records and cited references were exported to avoid bias from database updates. Duplicates and inconsistencies were removed to finalize the dataset. Two independent researchers conducted and validated the data collection process to ensure reliable results.

Bibliometric analysis

For the bibliometric analysis and visualization, we used VOSviewer 1.6.20, CiteSpace 6.4. R1, R software, and SCImago Graphica 1.0.45 to analyze publication volume, countries/regions, institutions, journals, authors, and keywords. VOSviewer, a free program used to construct and visualize bibliometric maps[18], was employed to conduct collaborative analyses between institutions and authors, as well as keyword co-occurrence analysis. CiteSpace, which integrates information visualization techniques, bibliometrics, and data mining algorithms in interactive visualizations[19], was used to extract citation data patterns and perform keyword burst analysis. The R software package “bibliometrix”[20](version 4.3.0) (https://www.bibliometrix.org) was used to plot research hotspot maps. SCImago Graphica, a no-code tool for creating of complex visualizations through simple drag-and-drop interactions[21], was used to construct cooperation networks between countries/regions.

RESULTS

Quantitative analysis of publication

Based on our search strategy, a total of 4967 publications related to PLGC were identified (from 2004 to 2023). After screening, 4097 publications were included in the analysis, comprising 3492 articles and 605 reviews (Figure 1). Collectively, these publications were cited 116044 times, with an h-index of 137. Analysis of the annual publication volume showed that since 2007, the number of publications in the PLGC field has gradually increased. A sharp rise occurred after 2019, with the number of publications increasing from 211 in 2019 to 292 in 2022, representing a 1.38-fold increase (Figure 2A). This suggests that PLGC has gained increasing attention from researchers and contributed to the field’s development.

Figure 1  Flowchart illustrating the literature inclusion, exclusion, and analysis processes.

Figure 2 Quantitative analysis of publication and the co-authorship map of countries/regions and institutions. A: Annual number of publications for precancerous lesions of gastric cancer; B: Annual number of publications in the top 5 countries/regions; C: Co-authorship map of countries/regions. Each node represents a country/region, with the node size corresponding to the number of publications from that location. The connections between nodes represent collaborations, while the intensity of the color reflects the total link strength; D: Co-authorship map of institutions. The nodes in the network map represent institutions, and the size of each node is proportional to the number of publications. The thickness of the connecting lines between nodes indicates the strength of the co-authorship relationships, with colors indicating different clusters.

Analysis of country/region distribution

Research on PLGC has been conducted in 90 countries/regions. The top 10 countries are shown in Table 1, with China and the United States dominating this field, accounting for approximately 53% of the total publications. China led in publication volume with 1147 publications and an h-index of 59. However, the United States had the highest citation count, with 49603 citations and an h-index of 107. Following these countries were Japan (12.52%), South Korea (8.74%), and Italy (6.03%). The annual publication trends of the top five countries are shown in Figure 2B, where China has demonstrated substantial growth in publication volume over the past 5 years, whereas other countries have shown steady trends. A visual analysis of the collaboration between countries/regions is shown in Figure 2C, where the node size represents the number of publications from each country/region, the connections between nodes represent collaborations, and the intensity of the color indicates the strength of the collaborations (total link strength). The United States had the most collaborative publications with other countries, followed by Germany, Japan, the United Kingdom, the Netherlands, and China.

Table 1 Top 10 countries/regions and institutions in precancerous lesions of gastric cancer research.

Country	Count	Citation	H-index	Institutions	Count	Citation	H-index
China	1147	21150	59	Harvard University	130	6273	41
United States	1023	49603	107	Vanderbilt University	115	8495	45
Japan	513	19363	66	United States Department of Veterans Affairs	112	6810	44
South Korea	358	9249	50	Veterans Health Administration	109	6678	42
Italy	247	8659	50	Peking University	101	3323	30
Germany	245	13832	61	Seoul National University	90	3971	36
United Kingdom	182	12350	50	Universidade Do Porto	86	4682	38
Netherlands	142	10080	51	Harvard Medical School	81	4338	35
France	126	7636	44	Shanghai Jiao Tong University	74	1272	20
Australia	117	7044	40	University of Texas System	70	3402	34

Analysis of institution distribution

Research on PLGC has been conducted in 200 institutions. The top 10 institutions are listed in Table 1. Harvard University (n = 130) and Vanderbilt University (n = 115) had the highest publication volumes. Vanderbilt University had the highest citation count, with 8495 citations and an h-index of 45. The top 10 institutions were primarily located in the United States (n = 6), followed by China (n = 2), South Korea (n = 1), and Portugal (n = 1). An analysis of collaborations between institutions is shown in Figure 2D, where the node size represents the number of publications by each institution, and the thickness of the connecting lines between nodes indicates the strength of the co-authorship relationships. Among the top 10 institutions, Vanderbilt University in the United States had the most collaborations, with strong ties to other institutions. This was followed by Seoul National University in South Korea and Peking University in China.

Analysis of journal distribution

Research on PLGC has been published across 200 journals, with publication counts ranging from 4 to 168. The top 10 journals are listed in Table 2. The World Journal of Gastroenterology ranked first, with 168 publications, followed by Digestive Diseases and Sciences (n = 77), Gastroenterology (n = 71), and Gastrointestinal Endoscopy (n = 71). Seventy percent of the journals belong to the Q1 quartile of the Journal Citation Reports rankings.

Table 2 Top 10 journals in precancerous lesions of gastric cancer research.

Journal	Count	JCR (2023)	IF (2023)
World Journal of Gastroenterology	168	Q1	4.3
Digestive Diseases and Sciences	77	Q2	2.5
Gastroenterology	71	Q1	25.7
Gastrointestinal Endoscopy	71	Q1	6.7
Endoscopy	66	Q1	11.5
PLOS ONE	59	Q1	2.9
Gut	58	Q1	23
American Journal of Surgical Pathology	54	Q1	4.5
Human Pathology	52	Q2	2.7
Surgical Endoscopy and Other Interventional Techniques	48	Q2	2.4

JCR: Journal Citation Reports; IF: Impact factor.

Analysis of authors distribution

A statistical analysis identified the top 10 authors contributing in PLGC research (Table 3). Mario Dinis-Ribeiro led with 56 publications, followed by Wei-Cheng You (n = 53) and M Blanca Piazuelo (n = 52). The most frequently cited author was Timothy C Wang, with 4780 citations and an h-index of 30. Among the top 10 authors by publication volume, five were from the United States, three from China, and one each from Portugal and the Netherlands. A visualization of the collaboration network between the authors is shown in Figure 3A.

Figure 3 Co-authorship map of authors, highly cited publications, and analysis of keywords. A: Co-authorship map of authors; B: Changes in citation volume of the top 10 highly cited publications over time; C: Co-occurrence map of keywords. In the network map, the nodes represent keywords, with node size proportional to the frequency of each keyword. The thickness of the connecting lines between nodes indicates the strength of the co-authorship relationships, while colors represent different clusters.

Table 3 Top 10 authors in precancerous lesions of gastric cancer research.

Author	Country	Count	Citation	Average per item	H-index
Mario Dinis-Ribeiro	Portugal	56	4478	83.66	31
Wei-Cheng You	China	53	2018	40.23	21
M Blanca Piazuelo	United States	52	3096	61.81	29
Kai-Feng Pan	China	45	1939	45.18	21
Timothy C Wang	United States	41	4780	119.1	30
Gregory Y Lauwers	United States	40	1499	38.83	22
Richard M Peek	United States	38	3637	97.58	29
Pelayo Correa	United States	35	3298	96.11	26
Ernst J Kuipers	Netherlands	34	3521	106.29	24
Jun-Ling Ma	China	33	1520	48.18	17

Analysis of highly cited papers

A statistical analysis of the top 10 highly cited papers in PLGC research is presented (Table 4), comprising two European guidelines[7,22], two guidelines from the American College of Gastroenterology[23,24], and one guideline from the British Society of Gastroenterology[25]. The remaining papers focused on topics such as H. pylori infection[26], inflammation[27], and biomarkers[28]. A visualization of the citation data for these papers is shown in Figure 3B.

Table 4 Top 10 most cited references in precancerous lesions of gastric cancer research.

Title	First author	Journal	Year	Total citations
ACG Clinical Guideline: Genetic Testing and Management of Hereditary Gastrointestinal Cancer Syndromes	Sapna Syngal	American Journal of Gastroenterology	2015	1013
Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline	Pedro Pimentel-Nunes	Endoscopy	2015	767
Association Between Helicobacter pylori Eradication and Gastric Cancer Incidence: A Systematic Review and Meta-analysis	Yi-Chia Lee	Gastroenterology	2016	561
Management of epithelial precancerous conditions and lesions in the stomach (MAPS II): European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter and Microbiota Study Group (EHMSG), European Society of Pathology (ESP), and Sociedade Portuguesa de Endoscopia Digestiva (SPED) guideline update 2019	Pedro Pimentel-Nunes	Endoscopy	2019	539
Inflammation and cancer	Mariko Murata	Environmental Health and Preventive Medicine	2018	381
British Society of Gastroenterology guidelines on the diagnosis and management of patients at risk of gastric adenocarcinoma	Matthew Banks	Gut	2019	334
Plasma long noncoding RNA protected by exosomes as a potential stable biomarker for gastric cancer	Qier Li	Tumor Biology	2015	324
Gastric cancer: Prevention, screening and early diagnosis	Victor Pasechnikov	World Journal of Gastroenterology	2014	304
AGA Institute Clinical Practice Update: Endoscopic Submucosal Dissection in the United States	Peter V Draganov	Clinical Gastroenterology and Hepatology	2019	264
Plasma circular RNA profiling of patients with gastric cancer and their droplet digital RT-PCR detection	Tianwen Li	Journal of Molecular Medicine-Jmm	2018	209

Analysis of keywords

A statistical analysis of keywords in PLGC research was conducted to examine co-occurrence, bursts, and hotspot predictions. Using VOSviewer software, a co-occurrence analysis of keywords was performed (Figure 3C), dividing the network into three clusters that illustrated the foundational knowledge structure of the field. The blue cluster includes terms like “intestinal metaplasia”, “atrophic gastritis”, “helicobacter pylori”, “risk”, and “prevalence”, primarily related to the early pathological stages or risk factors of PLGC development. The red cluster is mainly associated with the mechanisms of PLGC development, with keywords such as “expression”, “inflammation”, “carcinogenesis”, “mutations”, and “apoptosis”. The green cluster focuses on diagnosis and treatment, including terms like “diagnosis”, “classification”, “management”, “endoscopic submucosal dissection”, and “follow-up”. We also constructed a visual representation of keyword bursts to demonstrate the evolution of keyword trends in the PLGC field over time (Figure 4). Early bursts focused on terms such as “gene expression”, “cell proliferation”, and “microsatellite instability”. In the mid-phase, keywords like “animal model”, “gastroesophageal reflux disease”, and “narrow band imaging” emerged. In recent years, research hotspots have shifted to terms like “artificial intelligence”, “case report”, and “gastric microbiota”. Hotspot prediction using R software yielded similar results (Figure 5).

Figure 4  Top 25 keywords with the strongest citation bursts in precancerous lesions of gastric cancer research.

Figure 5  Trend topics in precancerous lesions of gastric cancer research.

DISCUSSION

As the “golden turning point” in the development of intestinal-type gastric cancer, the early detection and treatment of PLGC can reduce the incidence of gastric cancer. This study reviews nearly 20 years of research on PLGC, aiming to summarize the current state of the research using statistical data, track research hotspots, and predict future trends.

Overview of research findings

Over the past 20 years, the number of publications on PLGC has shown a general upward trend, with a substantial increase in 2019. This indicates growing interest from researchers in PLGC. A review of the literature reveals that 2019 saw the release of updated European guidelines for the management of epithelial precancerous conditions and lesions in the stomach (MAPS II), providing a reference framework for the diagnosis and treatment of PLGC[7]. In the same year, the United States released an update on clinical practices for endoscopic submucosal dissection, addressing many treatment-related issues concerning PLGC[24]. These developments reflected the increasing attention on PLGC. Over the last two decades, China and the United States were the most prolific contributors in terms of publication volume, with the United States maintaining close collaborations with other countries. Japan, South Korea, and Italy followed in publication output. Harvard and Vanderbilt Universities in the United States published the most papers, followed by other contributing institutions in China (n = 2), South Korea (n = 1), and Portugal (n = 1). The most prolific author was Mario Dinis-Ribeiro from Portugal, with 56 publications, followed by Wei-Cheng You from China. Among the top 10 authors, five were from the United States. In summary, the United States has made notable contributions to the PLGC field, while China and other countries have also played substantial roles. However, enhancing the production of high-quality publications and promoting international collaborations are necessary.

Analysis of the current state of research

The establishment of the concept of precancerous lesions has undergone a long evolution. In 1971, the WHO classified gastric cancer precursors into precancerous diseases and precancerous lesions, introducing the concept of precancerous lesions to describe pathological changes prone to transformation into cancerous tissue. In 1992, Correa et al[5] proposed the cascade model for the development of intestinal-type gastric cancer, emphasizing the multi-step and multi-stage process: Inflammation, atrophy, metaplasia, dysplasia, and carcinoma. This model highlight the complexity of the process. After approximately two decades of research, in 2012, Europe formulated guidelines on precancerous conditions and lesions in the stomach, defining chronic atrophic gastritis and intestinal metaplasia as precancerous conditions, and dysplasia as the most direct precancerous lesion[6], which led to a series of extensive clinical and basic research efforts. In 2019, the European guideline was updated, further categorizing dysplasia/intraepithelial neoplasia into low-grade and high-grade forms[7]. That same year, the WHO recommended the use of the term “dysplasia” in the gastrointestinal tract[29], a terminology that has gradually been accepted and applied by researchers. To gain a clearer understanding of the research focuses in the field of PLGC, we employed bibliometric methods to review PLGC-related research over the past 20 years. By integrating the keyword clustering results, we identified the following current research themes in the PLGC field: Risk factors, pathogenesis, as well as diagnosis and treatment.

Risk factors: H. pylori is recognized as a group 1 carcinogen, with a global infection rate of 44.3%[30]. Once H. pylori establishes persistent colonization of the gastric mucosa, it contributes to the development of PLGC through inflammatory responses, free radical production, DNA damage, and molecular events[31]. Pathogenic factors of H. pylori, such as cytotoxin-associated gene A, vacuolating cytotoxin A, and H. pylori-neutrophil-activating protein, exhibit proinflammatory activity, and the accumulation of an inflammatory microenvironment is a key factor in the progression of PLGC[32]. A 16-year follow-up study demonstrated that individuals with a persistent H. pylori infection for 16 years had a substantially higher likelihood of progressing to a more advanced diagnosis (P= 0.001)[33]. H. pylori eradication therapy has been shown to benefit patients with PLGC[34]. In addition to H. pylori, other risk factors for PLGC include age, gender, host genetic variations, and a high-salt diet[7,35].

Pathogenesis: The pathogenesis of PLGC, as identified through keyword clustering in this study, primarily focuses on inflammation, immune microenvironment, metaplasia, cell proliferation, stem cells, gene mutations, and gut microbiota. Chronic inflammation catalyzes cancer development[36] and is associated with genotoxicity, abnormal tissue repair, proliferative responses, invasion, and metastasis[37]. In the inflammatory microenvironment, reactive oxygen species and reactive nitrogen species released by inflammatory cells can damage cells, leading to DNA double-strand breaks, which in turn cause gene mutations, tumorigenic transformation, or cell death[38]. Various immune cells, such as neutrophils, T lymphocytes, macrophages, and fibroblasts, play crucial roles in the progression of PLGC[32]. Factors such as H. pylori infection, bile reflux, and alcohol consumption induce gastric mucosal damage, creating an environment conducive to metaplasia through inflammation and reactive oxygen species production. Long-term metaplasia, caused by sustained exposure, is a risk factor for dysplasia and malignant transformation[39]. Spasmolytic polypeptide-expressing metaplasia represents another form of intestinal metaplasia, with studies showing that interleukin-33 derived from epithelial cells stimulates specialized innate immune cells to produce interleukin-13, which induces chief cells to transdifferentiate into spasmolytic polypeptide-expressing metaplasia, followed by the loss of parietal cells from the gastric corpus[40].

Cancer has been described as a “wounds that will not heal”, where precancerous cells hijack normal regenerative pathways to promote abnormal growth[35]. With advancements in stem cell research, recent studies have identified dysplastic stem cell populations as novel cancer-initiating cells responsible for neoplastic transformation. Xenograft studies showed that CD44v6^neg/CD133⁺/CD166⁺ (double positive) dysplastic stem cells can clonally evolve into various types of gastric adenocarcinoma, promoting cancer cell heterogeneity through the acquisition of additional gene mutations and recruitment of the tumor microenvironment[41]. The interaction between gut microbiota and epithelial cells is crucial for maintaining intestinal barrier function[42]. Microbial communities and their metabolites play vital roles in maintaining immune homeostasis[43]. Studies indicated that the immune microenvironment and microbiota in precancerous tissues undergo changes, which have become focal points for researchers[11]. Recently, researchers discovered that Streptococcus infection can promote gastric inflammation and dysplasia in mice, directly interacting with gastric epithelial cells through the Treponema pallidum membrane protein C-annexin A2-mitogen-activated protein kinase axis to induce gastric tumorigenesis. This represents a new and significant exploration following the discovery of H. pylori[15]. Additionally, other areas of interest for researchers include bile acids, glycolysis, autophagy, and ferroptosis[44].

Diagnosis and treatment: Accurate diagnosis and grading of PLGC are crucial. With the advancements in modern endoscopy, conventional white-light endoscopy alone cannot reliably distinguish and diagnose PLGC. Clinical practice often incorporates high-definition chromoendoscopy, electronic chromoendoscopy, and magnifying endoscopy to enhance lesion detection accuracy[7,45]. The diagnosis of PLGC also requires pathological evidence, with the selection of biopsy tissue and the judgment of the pathologist being key factors in making an accurate diagnosis. Guidelines recommend that patients with endoscopically confirmed dysplasia should undergo endoscopic treatment. In cases in which no endoscopic lesions are defined, immediate use of chromoendoscopy (virtual or dye-based) is advised for high-quality endoscopic reevaluation[7]. High-quality endoscopic follow-up should be emphasized in patients with different pathological stages. Furthermore, H. pylori eradication should be a consistent component throughout the treatment of precancerous lesions, providing benefits at all stages, whether in chronic atrophic gastritis, intestinal metaplasia, or post-endoscopic treatment.

Research hotspots and trend predictions

In 2018, the National Cancer Institute launched a large-scale research project called the Precancer atlas, aiming to provide spatiotemporal histological and multi-omics mapping strategies for comprehensive characterization of the molecular and cellular features of premalignant lesions and their microenvironment[46]. However, its workflow is complex and requires collaboration across multidisciplinary teams, and the project is still ongoing[47]. Single-cell technology allows for the examination of differences between cell types and states within samples. Using RNA sequencing at single-cell resolution, researchers have characterized heterogeneous cell populations in precancerous lesions and gastric cancer, identifying enriched cyclin D1 mutations in the premalignant disease state, as well as discovering cancer-associated fibroblasts with pro-stemness properties[48]. Spatially resolved analysis techniques can evaluate differences between regions within lesions, changes in tissue structures of different cell types, and alterations in cell neighborhoods and tissue architecture. Researchers have employed bulk, single-cell, and spatial profiling strategies to attempt to map the complex processes of precancerous lesions[49]. With the advancement of aging and epigenetics research, a key molecular marker known as “epigenetic aging” has been associated with precancerous risk and initiation and has been shown to play a crucial role in predicting the timing of cancer onset in patients with precancerous lesions[35,50,51]. The interactions between the immune microenvironment, gut microbiota, and their metabolic products in precancerous lesions remain a hotspot for ongoing research[11].

Based on the above analysis, we predict that the mechanisms of PLGC development and molecular biomarkers of PLGC will remain key areas of ongoing research. Future research should focus on gut microbiota, immune microenvironment, metabolic reprogramming, and epigenetics. Emerging technologies, such as single-cell sequencing, spatially resolved analysis, multi-omics analysis, artificial intelligence, and machine learning, will further enhance research into the mechanisms of PLGC. Traditional formulas or chemical components have been shown to be effective in treating PLGC, demonstrating unique advantages through multiple pathways and multitarget comprehensive interventions[52].

Limitations

Although we strictly adhered to bibliometric research methods, our study has certain limitations: (1) Selection bias: Our literature search was conducted using the WoSCC database and included only articles and reviews published in English, which may lead to incomplete literature retrieval; (2) Time bias: This study only included literature from 2004 to 2023. Given the rapid pace of research updates, it may not fully reflect the latest scientific trends and findings; and (3) Methodological bias: As the volume of data increases and the demand for more complex analytical methods grows, bibliometric analysis still has limitations in terms of the depth and breadth of data analysis. Future studies could integrate big data and artificial intelligence technologies to provide a more objective, accurate, comprehensive, and multi-faceted representation of the current state of research in the field.

CONCLUSION

This study systematically analyzed the current state of PLGC research on a global scale, highlighting research status and emerging trends in PLGC over the past 20 years and providing valuable references for future studies. Based on publication volume and bibliometric analysis, the number of publications in this field is expected to continue to increase. Future research should focus on early identification, precise diagnosis, mechanistic exploration, and drug development for PLGC. Key topics include gut microbiota, immune microenvironment, metabolic reprogramming, and epigenetics. Continued emphasis on multidisciplinary and multicenter collaborations is necessary to leverage advanced modern technologies, as well as subsequent developments in big data and artificial intelligence, to achieve early detection, diagnosis, and treatment. These efforts aim to prevent the malignant transformation of PLGC into gastric cancer, bringing more hope to patients.