Research trends in epigenetic studies on lung cancer: a bibliometric and visual analysis of the past decade

Introduction

Lung cancer is one of the most common cancers worldwide, moreover, reports have showed that lung cancer also possesses high mortality rates with over one million people die from lung cancer each year. It not only poses a serious threat to human health but also imposes a significant burden on healthcare resources and the broader economy (1). Despite the significant health threat, the underlying mechanisms are still not fully understood, and its treatment strategies have long been a major focus of medical research (2). In recent years, with the development in molecular biology and genomics, research on the molecular mechanisms of lung cancer has advanced rapidly, and novel therapeutic targets have been discovered (3,4).

Epigenetics is the study of heritable changes in gene expression that occur without alterations to the DNA sequence (5). Key mechanisms include DNA methylation, histone modifications, and the regulation of gene expression by non-coding RNAs (ncRNAs) (6). Epigenetic modifications have been widely reported in many pulmonary diseases including lung cancer, pulmonary hypertension, lung fibrosis, etc., moreover, it also plays a crucial part in the initiation, progression, and metastasis of lung cancer (7). For instance, aberrant DNA methylation can silence tumor suppressor genes, while dysregulated ncRNAs can promote cancer cell proliferation and inhibit apoptosis (8). Epigenetic changes also hold great promise in lung cancer treatment, Khan and colleagues pointed out the therapeutic potential of epigenetic modifications of microbial metabolites and toxins in lung cancer (9-11). Jiang et al.’s research indicated the significant potential of long non-coding RNA (lncRNA) methylation modifications, controlled by epigenetic mechanisms, in the clinical application of lung cancer (10). Specifically, the 2024 Nobel Prize in Physiology or Medicine, awarded to Victor Ambros and Gary Ruvkun for their discovery of microRNAs (miRNAs) and their role in post-transcriptional gene regulation (12), further underscores the importance of epigenetics in biomedical research. MiRNAs, as key components of the epigenetic landscape, exemplify the transformative potential of this field. Despite the rapid evolution of epigenetic research, a systematic analysis of key advancements and emerging research hotspots remains limited.

Bibliometrics is a quantitative analytical method used to examine patterns and trends in scientific publications (13). In the field of lung cancer epigenetics, bibliometric analysis can systematically identify research hotspots, key contributors, and collaborative networks. This approach not only highlights the current focal points of the research domain but also provides valuable insights into future directions. Although there is currently a bibliometric article on the epigenetics of lung cancer, it only analyzes the top 100 most-cited papers in the field, including review articles (14). While this approach highlights high-impact research, it fails to comprehensively reflect the overall trends and research hotspots within the domain. Moreover, the wide temporal span of the analysis may hinder timely insights into the most recent directions in the field.

Therefore, this study aims to address these gaps by conducting a bibliometric analysis of original research articles published in the past decade. By integrating bibliometric methods with knowledge mapping, it seeks to provide a comprehensive overview of the current state and emerging trends in the field of lung cancer epigenetics. We present this article in accordance with the BIBLIO reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-684/rc).

Methods

Search strategies and data collection

This study conducted a comprehensive literature search using the Web of Science Core Collection (WoSCC) database, recognized as a globally authoritative source for bibliometric research (15). To avoid potential biases caused by database updates, all searches were completed on November 4, 2024, with the time span limited to publications between 2015 and 2024. The research focused on lung cancer and epigenetics studies, and the detailed search strategy is provided in Table S1. During the screening process, the publication language was restricted to English, and the document type was limited to articles. The selected bibliographic data were exported in the formats of “Full record and cited references” and “Plain text” for subsequent analysis. Extracted information included publication year, citation frequency, author details, affiliations, countries/regions, journal names, and keywords.

Statistical analysis

Relevant data was retrieved from the literature bibliographies, and the bibliometric indicators including annual publication counts, citation frequencies, average citation frequencies, journal names, journal impact factors (IFs), publication countries/regions, institutions, and authors were organized using Microsoft Excel.

Visualization tools including VOSviewer (version 1.6.20), CiteSpace (version 6.3.R1), and R software (version 4.4.1) were used in this study. VOSviewer was employed to visualize and explore the intricate academic relationships including co-authorships, citations, co-citations, and keyword co-occurrence analysis (16). In these visual representations, node size corresponds to publication count, line thickness to link strength, and node color to different clusters or periods. CiteSpace was utilized for the keyword burst analysis (17). The time slice was set to 1 year; node types: keywords. When the node type was keywords: the threshold (top N in each slice) =5, pruning = pathfinder + pruning merged networks. The resulting visualizations illustrated keyword relationships and dynamics within the field. Node size in the visualizations reflects the number of publications, link thickness indicates connection strength and node colors represent different clusters or time periods (18). The Hirsch index (H-index) and the IF were extracted from the most recent Journal Citation Reports (JCRs). The H-index is a recognized measure of the research impact of an individual or a nation, signifying that an individual or nation has published H papers, each cited at least H times in other publications (19). Additionally, the m-index and g-index are also used for comprehensive evaluation (20,21).

Results

An overview of publications in research of epigenetic research in lung cancer

This study conducted a comprehensive bibliometric analysis of the literature in the field of lung cancer epigenetics, with the detailed process illustrated in Figure 1. This study initially identified 16,264 relevant research articles, after the exclusion of reviews (n=2,777), meet abstract (n=531), retracted publications (n=366), and other publications according to the inclusion criteria, 12,117 eligible publications were included for final analysis. Among the 12,117 publications, this study identified 37,231 authors, 1,237 journals, and collectively cited 261,570 references.

Figure 1 Flow chart.

The trends in the annual and cumulative publication numbers in lung cancer epigenetic research from 2015 to 2024 were systematically analyzed and shown in Figure 2. Over the past decade, publication numbers have reached a plateau and peaked in 2020 (n=1,591). And the cumulative number of publications is still steadily increasing. An exponential growth function was used to evaluate the correlation between the cumulative number of publications and the years, revealing a strong relationship (R²=0.9952).

Figure 2 Annual number of publications.

Analysis of the countries

From a country perspective, the top three countries with the largest number of publications were China, USA, and Japan, with 8,935, 604, and 234 publications, respectively. These three countries also had the top three total citations of 218,288, 38,840, and 7,185, respectively. The results also revealed that the UK, the Netherlands, and Australia showed the highest proportion of multiple-country publications at 63.9%, 62.9%, and 53.8%, while the proportion of multiple-country publications for China and Japan were 6.4%, and 14.9%, respectively (Table S2 and Figure 3A). Among the 90 countries involved in international collaborations with a minimum of 1 article, the USA had the highest number of collaborations with other countries [1,493], followed by China [1,086] and the UK [451], indicating these countries showed extensive collaboration with other countries (Figure 3B).

Figure 3 Visualization of countries. (A) Publications distribution by country. (B) Visualization map depicting the collaboration among different countries. MCP, multiple country publications; SCP, single country publications.

Analysis of the institutions

Nanjing Medical University in China (n=1,271) emerged as the leading institution, followed by Central South University in China (n=795), and Zhengzhou University (n=683). The study also revealed that among the top 10 institutions with the most articles, 9 were in China, and one was from the USA (Figure 4A). In addition, Figure 4B illustrates the collaborative relationships among 169 institutions that have published a minimum of 25 documents. Nanjing Medical University exhibits the highest number of collaborations with other institutions, totaling 505, followed by the Chinese Academy of Sciences with 375 and Shanghai Jiao Tong University with 367.

Figure 4 Visualization of institutions. (A) Top ten institutions by article count. (B) Visualization map depicting the collaboration among different institutions.

Analysis of journals

The top 20 journals with the highest H-index were shown in Table S3. Among the high-impact journals, Oncotarget ranks first with H-index of 67, the total publications (n=409) also ranked first, while the total citations (n=12,244) was in second place, indicating its pivotal role in disseminating influential research in this field. Following that, Tumor Biology and Biomedicine & Pharmacotherapy (2023 IF =6.9, JCR Q1) had the second and third highest H-index of 49 and 47. Besides, Oncology Letters (H-index =36, 2023 IF =2.5, JCR Q3) was notable for the high total publication (n=350), Cancer Research (H-index =37, 2023 IF =12.5, JCR Q1) received most citations (n=13,177).

Analysis of the authors

Li Y (H-index =50) and Zhang Y (H-index =48) ranked first and second based on H-index. In terms of total publications, Zhang Y authored the highest number of articles (n=309), followed closely by Wang Y and Wang J, who published 300 and 282 articles, respectively. An analysis of total citations indicated that Zhang Y received 8,470 citations, securing the first rank, while Li Y and Wang J garnered 7,861 and 7,614 citations, placing them in the second and third positions, respectively (Table S4). Among the 107 authors involved in international collaborations with a minimum of 23 articles, Yin Z has the highest number of collaborations with other authors [69], followed by Zhou B [67] and Li H [58] (Figure 5).

Figure 5 Visualization map depicting the collaboration among different authors.

Analysis of the keywords

The keyword co-occurrence network analysis highlights central nodes such as “expression”, “proliferation”, and “metastasis”, with strong total link strengths of 19,632, 12,703, and 10,919, respectively. The color coding reflects research hotspots across different time periods. Prior to 2018, frequently occurring keywords included “tumor suppressor”, “gastric cancer”, “colorectal cancer”, and “prostate cancer”, suggesting a research focus on the association between lung cancer and other malignancies. Between 2018 and 2020, the emphasis shifted toward mechanisms underlying lung cancer, as indicated by keywords such as “metastasis”, “expression”, and “microRNAs”. Post-2020, the predominant keywords—“migration”, “lncRNA”, and “noncoding RNA”—demonstrate a growing interest in the functional roles of noncoding RNAs and their diagnostic and prognostic implications. This trend underscores the rapid advancements in RNA research within the field of lung cancer and epigenetics (Figure 6A).

Figure 6 Visualization of keywords. (A) Visual analysis of keyword co-occurrence network analysis. (B) Top 20 keywords with the strongest citation bursts.

The results for the burst keywords are shown in Figure 6B. Early bursts, such as “microRNA expression” (2015–2017, strength =26.32) and “tumor suppressor” (2015–2018, strength =22.53), highlight foundational research in molecular biology and align well with the findings from the keyword co-occurrence network analysis. In contrast, more recent bursts, including “validation” (2022–2024, strength =15.08) and “metabolism” (2022–2024, strength =15.01), reflect a growing emphasis on validating prior findings and exploring novel metabolic characteristics of lung cancer. Notably, among all burst keywords, “tumor microenvironment” [2021–2024] exhibited the highest burst strength (31.54), underscoring its significant research potential in the field of lung cancer and epigenetics.

Discussion

Overview of the findings

The bibliometric analysis of epigenetic research in lung cancer has demonstrated steady growth in the field over the past decade. With a total of 12,117 publications analyzed, the findings indicate that the USA and China are dominant contributors. The USA leads in total citations, emphasizing its strong academic influence, while China shows extensive research activity with the highest publication count. Journals such as Chest and European Respiratory Journal have emerged as pivotal publication platforms, reflecting their role in disseminating high-impact studies.

The bibliometric analysis of epigenetic research in lung cancer over the past few decades reveals a complex and evolving landscape. Overall, the number of publications has increased steadily, peaking around 2020, which likely reflects a concentrated burst of interest in the epigenetic mechanisms underlying cancer biology, this trend is also consistent with the research hotspots of Li and colleagues toward trends in tumor epigenetics (22). However, the decline in publication volume after 2020 may not indicate a loss of research interest, but rather a shift in focus within the field. This may be due to the maturation of certain research themes or the emergence of new technologies, disease models, or therapeutic targets that redirect the research agenda, such as immunotherapies (23,24) or studies on other malignancies (25). As previous mentioned, the 2024 Nobel Prize in Physiology or Medicine, awarded to Victor Ambros and Gary Ruvkun for their discovery of miRNA and its role in post-transcriptional gene regulation, further emphasizes the continued significance of epigenetics (12). MiRNA is a key component of the epigenetic landscape, and their groundbreaking discoveries underscore the ongoing importance of this field. It is reasonable to expect that miRNA-related breakthroughs will drive a new wave of research in epigenetics, especially in the context of cancer, suggesting that the future of epigenetic research in lung cancer could experience renewed momentum in the coming years.

Research hotspots

RNAs and epigenetics of lung cancer

Keyword analysis has illuminated key research hotspots, with earlier studies focusing on mechanisms such as “DNA methylation” and “promoter hypermethylation”. Over time, the field has evolved to include more complex regulatory elements, such as miRNAs, ncRNAs, lncRNAs, and circular RNAs (circRNAs). These molecules not only deepen our understanding of gene regulation but also open avenues for novel diagnostics and treatments. Besides, with the discovery of lncRNAs and circRNAs, their roles in tumor progression, metastasis, and resistance have become prominent. For example, a recent finding revealed the complete mechanism of lncRNA PVT1 and its potential to improve the prognosis of lung cancer patients (26). Advances in epigenetic inhibitors have highlighted translational applications, particularly those targeting DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), Heo et al. reported that by using DNA methylome and single-cell transcriptome analyses, they revealed cytidine deaminase as potential drug target in non-small cell lung cancer (NSCLC) (27), while Han and colleagues found aberrant DNA methylation in SMAD3 promoter could increase the radiosensitivity in NSCLC (28). These agents are being investigated in combination with immunotherapy to overcome resistance. Moreover, one study discussed the role of HDAC2 in tumorigenesis and anticancer drug resistance (29), while another investigated how metformin inhibited DNMT expression by upregulating miR-148/-152 family members in NSCLC cells (30).

Tumor microenvironment (TME) and epigenetic of lung cancer

Recent research highlights include TME, emerging as a central focus, studies explore how epigenetic modifications influence immune cell infiltration, stromal interactions, and chemoresistance (31). The intricate crosstalk within the TME offers promising targets for immunotherapies. For instance, Zhao’s team utilized high-permeability tellurium nanoparticles as therapeutic agents to reshape the TME, achieving enhanced therapeutic efficacy (32). The research team led by Hua-Fei Chen employed cyclin-dependent kinase 5 (CDK5) to alter the TME, consequently affecting the resistance of lung cancer to radiotherapy (33). Another recent study has demonstrated that bacteria-driven TME-sensitive nanoparticles can enhance the efficacy of lung cancer chemotherapy (30).

Future research trends

Biomarkers and epigenetic of lung cancer

Future directions in epigenetic research for lung cancer are likely to focus on the following areas: combining epigenomics with transcriptomics, proteomics, and metabolomics to construct comprehensive disease models, this approach could reveal new biomarkers and therapeutic targets (34,35). The use of monotherapy and combination immunotherapy with multiple drugs is expected to extend the life expectancy of patients and reduce chemotherapy-related side effects, the combination treatment of dabrafenib and trametinib has shown significant efficacy in patients with metastatic NSCLC that is caused by BRAFV600E mutation and unresponsive to standard therapy (36). Exploring the role of epigenetic modifications in developing lung cancer drug resistance, a review article by Munteanu et al. discusses the research trends in the field of epigenetic modifications related to lung cancer drug resistance (37). These studies are expected to lead to further advances in the understanding of the interplay between epigenetic regulation and immune responses.

Metabolism and epigenetic of lung cancer

Understanding cellular metabolism holds immense potential for developing new classes of therapeutics that target metabolic pathways in cancer, and the metabolic patterns are significantly different in neoplastic and normal cells. However, the understanding of metabolic pathways in neoplastic cells is still lacking, especially for the epigenetic features of different cancer. With the rapid development of novel techniques on metabolism analysis, Wang et al. revealed that Methionine is a metabolic dependency of tumor-initiating cells (38); Zhang et al. showed that NSUN2-mediated 5-methylcytosine modification induced metabolic reprogramming and cell cycle by promoting the mRNA stabilities, indicating the epigenetic modification may be a potential treatment target for the cancer (39). Moreover, Meng and colleagues showed that beta-1,3-N-acetylglucosaminyltransferase 5 (B3GNT5) and galactose-3-O-sulfotransferase 1 (GAL3ST1) could differentially regulate lung cancer growth and progression through sphingolipid metabolism (40), histone modification was another important modification method, Zhang et al. revealed that histone modification was a potent diagnostic and therapeutic targets in NSCLC (41). This evidence proves that metabolism possesses significant research potential for future lung cancer treatment targets.

Limitations

While this study provides valuable insights, certain limitations must be acknowledged. Firstly, the reliance on citation metrics may not fully capture clinical impact or emerging significance, only top ranked burst keywords and articles were discussed, while other studies also provide valuable information. Secondly, China researchers have dominated this research field and many research results were published in Chinese, restricting the analysis to English-language publications may have excluded relevant studies, potentially introducing bias. Thirdly, this study only included data from the WoSCC database and did not incorporate other major databases such as PubMed or Scopus, which may limit the comprehensiveness of the analysis. Additionally, NSCLC has been researched for more than several decades, focusing on the research of the past decade may limit the historical context of long-term trends. Finally, future studies should incorporate broader data sources and explore methods to assess the translational impact of findings beyond academic citations.

Conclusions

This bibliometric analysis in the field of lung cancer and epigenetics revealed China and Nanjing Medical University as the top contributors among countries and institutions, respectively. Li Y was the author with the highest H-index. Besides, research hotspots have evolved dynamically over time, transitioning from initial focuses like “microRNA expression” and “tumor suppressor” to more recent areas such as “tumor microenvironment”, “immune infiltration”, and “circular RNA”.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the BIBLIO reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-684/rc

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-684/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-684/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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