Abstract
Background
Ovarian cancer ranks first among malignant tumors in the female reproductive system. Ferroptosis plays a crucial role in the occurrence, development, and treatment of ovarian cancer. However, research focusing on the bibliometric analysis of ferroptosis in ovarian cancer remains scarce. This study employs bibliometric methods to analyze research trends related to ferroptosis in the field of ovarian cancer, providing direction for scholars and clinical practitioners.
Methods
Articles regarding ferroptosis and ovarian cancer were retrieved from the Web of Science Core Database up to November 6, 2024. After rigorous screening, bibliometric analysis utilized VOSviewer and CiteSpace, while CoreMine facilitated text mining in relation to drugs and genes significantly associated with ovarian cancer and ferroptosis.
Results
The publication volume of articles on ferroptosis and ovarian cancer has shown a yearly increase, significantly surging after 2022. The three countries with the highest publication outputs are China, the United States, and Japan. The top ten institutions with the most publications are all from China. The ten most frequently mentioned keywords are ferroptosis, ovarian cancer, cell death, apoptosis, expression, death, iron, resistance, metabolism, and cells. Text mining reveals that cisplatin, along with the genes/proteins SLC7A11 and GPX4, significantly correlates with both ovarian cancer and ferroptosis.
Conclusions
Our article uses bibliometric methods to reveal publication trends, national distributions, regional collaborations, and recent research hotspots related to the correlation between ferroptosis and ovarian cancer. This study provides objective data as a reference for scientific research and clinical work concerning ferroptosis and ovarian cancer.
Keywords: Bibliometric analysis, Ferroptosis, Ovarian cancer, Publication
Introduction
The mortality rate of ovarian cancer ranks fifth among all cancers in women and stands as the leading cause of death among malignant tumors of the female reproductive system [1]. Due to its insidious onset, early-stage patients often lack specific symptoms and characteristics. Approximately 70% of patients are diagnosed at advanced stages, resulting in a five-year survival rate of only 30–40%. The clinical management of ovarian cancer includes various adjunctive therapies such as surgical intervention, combination chemotherapy, and targeted therapies [2]. In the absence of specific diagnostic methods, about 70% of patients are already in advanced stages at the time of diagnosis. Furthermore, multiple rounds of postoperative chemotherapy can lead to chemoresistance in ovarian cancer patients [3]. For those with advanced disease, tumor debulking and platinum-based combination chemotherapy form the cornerstone of treatment. Many patients achieve remission after first-line therapy, yet around 70% will experience recurrence within two to three years, requiring salvage treatment, with decreasing intervals between treatments ultimately leading to death [4].
Ferroptosis represents a novel form of cell death that is iron-dependent, morphologically and biochemically distinct from autophagy, apoptosis, and necrosis. Its primary characteristics include iron accumulation and lipid peroxidation, evident through retinal mitochondrial shrinkage, increased membrane density, and reduced or absent mitochondrial cristae [5]. Ferroptosis plays a crucial regulatory role in the pathophysiology of various diseases, including tumors, cancers, neurological disorders, ischemia-reperfusion injury, acute kidney injury, hematological disorders, and inflammatory diseases [6]. Emerging evidence suggests that triggering ferroptosis holds therapeutic potential in cancer treatment, particularly for eradicating aggressive malignancies resistant to conventional therapies [7]. Inducers primarily achieve this by inhibiting cysteine uptake and the synthesis of glutathione peroxidase 4 (GPX4), inducing lipid peroxidation, thus promoting ferroptosis in tumor cells. Additionally, several ferroptosis-related genes have been analyzed and identified as potential drug targets and prognostic indicators [8]. In ovarian cancer treatment, significant potential has emerged; for instance, a study explored the expression of the Wnt receptor Frizzled-7 (FZD7) in platinum-resistant ovarian cancer (OVCA) cells. The findings indicated that FZD7 positively regulates the glutathione metabolic pathway, including GPX4. After exposure to GPX4 inhibitors, FZD7 + platinum-resistant OVCA cells displayed increased likelihood of undergoing ferroptosis [9]. Correlations between ferroptosis inducers and PARP inhibitors have been noted in BRCA gene-expressing OVCA cells. PARP inhibition promotes ferroptosis in OVCA through a p53-dependent mechanism that obstructs SLC7A11 [10].
Bibliometric analysis employs statistical examination of publications and citation frequencies, providing researchers with objective and statistically significant data for further analysis. It helps define specific trends within a field and tracks the research profiles of different academic communities across various countries, institutions, authors, and journals [11]. Despite the abundant research on ferroptosis in ovarian cancer, a lack of bibliometric analysis hinders the understanding of application developments, hot topics, and future prospects in this domain. Therefore, this study employs bibliometric methods to search the Web of Science Core Collection database for relevant literature, analyzing research trends about ferroptosis in the field of ovarian cancer. This aims to furnish scholars with insights into recent advancements and breakthroughs regarding ferroptosis and ovarian cancer, guiding clinical practice and further exploration.
Methods
Literature search and screening strategy
A literature search was conducted within the Web of Science Core Collection database, spanning from its inception to November 6, 2024. This scoping review was executed in accordance with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines to uphold transparency and methodological rigor. The search strategy was developed based on established retrieval frameworks used in ferroptosis or ovarian cancer research [12, 13], utilizing the MeSH (Medical Subject Headings) database to ensure exhaustive identification of pertinent keywords. The search strategy employed the following query syntax: TS = ((ferroptosis OR ferropto*) AND (Ovarian Cancer* OR “Ovarian Carcinoma” OR “Ovarian Neoplasm*” OR “Cancer of Ovary” OR “Cancer of the Ovary”)). Inclusion criteria comprised studies pertaining to ferroptosis and ovarian cancer, with document types restricted to “article” and “review” and language limited to English. Exclusion criteria encompassed Editorial Material, Retracted Publication, Book Chapters, Correction, Meeting Abstract, Proceeding Paper, Publication With Expression Of Concern, Early Access, Letter, and Retraction (Fig. 1). To mitigate subjective bias, two independent authors performed the literature screening and data extraction. Discrepancies in paper selection were resolved through consensus with a third author.
Fig. 1.
Schematic representation of the literature search and selection methodology
Bibliometric analysis
Bibliometric and visualization analyses were conducted using Excel 2019, the online bibliometric analysis platform (https://bibliometric.com/), VOSviewer (v1.6.19), and CiteSpace (v.6.1.R6). Publication and citation metrics, including annual publication volume and citation frequency, were analyzed using Excel 2019 and the online bibliometric analysis platform (https://bibliometric.com/). VOSviewer (v1.6.19) was employed for the analysis of collaboration networks among countries, institutions, and authors. CiteSpace (v6.1.R6) was utilized for cluster analysis and the identification of emerging trends.
Text mining analysis
CoreMine Medical, a PubGene Company product, facilitates the indexing of textual data derived from the MEDLINE database, encompassing titles and abstracts available in PubMed. The CoreMine Medical online analysis platform (https://coremine.com/medical) can be employed for text mining analyses pertinent to ferroptosis and ovarian cancer. The “Filter by connection relevance” criterion is set at a p-value of less than 0.05. This approach allows for the identification of potential drug candidates and genes exhibiting statistically significant correlations with both ferroptosis and ovarian cancer, as documented in the literature.
Results
Analysis of annual publications
As of November 6, 2024, a total of 237 articles have been published in the WOS database, comprising 207 articles and 30 reviews. The first articles on ferroptosis and ovarian cancer appeared in 2017, totaling two. Prior to 2022, the number of publications remained low, with fewer than 50 articles published each year. However, after 2022, the number of published articles experienced a significant surge, reaching 73 in 2023, which is 36 times the output in 2017. By November 6, 2024, 67 articles have also been published (Fig. 2A). The daily publication rate shows that the average daily output in 2024 has exceeded that of 2023 (Fig. 2B). Calculating both the total annual publication volume and daily averages indicates that articles on the relationship between ferroptosis and ovarian cancer continue to rise each year, particularly after 2022, and the fitted curve suggests an ongoing upward trend (Fig. 2).
Fig. 2.
Analysis of annual publications. A Annual publications. B Daily average publication
Analysis of countries/regions
A total of 34 countries/regions contributed to this field. As shown in Fig. 3A, China dominates publication output with 169 articles, followed by the United States (n = 32) and Japan (n = 12). In terms of total citations, the top three countries are China (n = 2476), the United States (n = 2448), and Japan (n = 456).
Fig. 3.
Analysis of countries. A Top 10 countries by publication volume. B Annual publication of top 10 countries by publication volume. C Co-authorship analysis of 34 countries/regions
Longitudinal analysis (Fig. 3B) reveals a gradual increase in overall output, especially notable for China and the United States (Fig. 3B). It is worth mentioning that although Japan and Canada published fewer articles, both countries published work in 2017 and 2018, signaling their pioneering role in the area of ferroptosis and ovarian cancer (Fig. 3B).
Collaboration patterns (Fig. 3C) further demonstrate the United States has the highest level of international collaboration (Total link strength (TLS) = 21), followed by China (TLS = 17) and Canada (TLS = 10), with the collaboration between China and the United States being the strongest in the national collaboration network diagram (link strength = 8) (Fig. 3C).
Analysis of institutions
A total of 411 institutions published articles on ferroptosis and ovarian cancer. Notably, Chinese institutions dominate productivity: All ten top-publishing organizations are from China, collectively contributing 83 articles (35.0% of total publications). Leading this group are Central South University (12 articles), Shanghai Jiao Tong University (11), and Zhejiang University (11) (Table 1; Fig. 4A)(Table 1) (Fig. 4A). The three institutions with the most citations are Harvard University with 989 citations, Broad Institute with 987 citations, and Harvard Medical School with 564 citations (Table 1) (Fig. 4B).
Table 1.
Top 10 organizations by document numbers, citation numbers, and TLS numbers
| Top 10 organizations | ||||||
|---|---|---|---|---|---|---|
| Rank | By document numbers | By citation numbers | By TLS numbers | |||
| 1 | cent south univ | 12 | harvard univ | 989 | univ toronto | 27 |
| 2 | shanghai jiao tong univ | 11 | broad inst | 987 | harvard med sch | 24 |
| 3 | zhejiang univ | 11 | harvard med sch | 564 | shanghai jiao tong univ | 23 |
| 4 | guangzhou med univ | 8 | mit | 444 | dana farber canc inst | 21 |
| 5 | fudan univ | 8 | whitehead inst biomed res | 444 | brigham &womens hosp | 20 |
| 6 | nanjing med univ | 8 | uconn hlth | 334 | chinese acad sci | 20 |
| 7 | sun yat sen univ | 7 | jackson lab genom med | 325 | cent south univ | 19 |
| 8 | Chinese acad sci | 6 | wake forest univ | 315 | zhejiang univ | 19 |
| 9 | tongji univ | 6 | wake forest univ hlth sci | 315 | guangzhou med univ | 18 |
| 10 | zhengzhou univ | 6 | duke univ | 313 | harvard univ | 18 |
Fig. 4.
Analysis of institutions. A Density visualization of 411 organizations by document numbers. B Density visualization of 411 organizations by citation numbers. C Density visualization of 411 organizations by TLS numbers. D Network visualization of 411 organizations by TLS numbers
Collaboration analysis reveals distinct networks. The strongest collaboration is with the University of Toronto (TLS = 27), followed by Harvard Medical School (TLS = 24) and Shanghai Jiao Tong University (TLS = 23) (Table 1) (Fig. 4C). Additionally, a visual network of institutional collaborations among these 411 institutions demonstrates that the University of Toronto, Harvard Medical School, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, among others, form a closely-knit collaborative network (Fig. 4D, cluster in green).
Analysis of authors
A total of 1,656 authors contributed 237 articles on ferroptosis and ovarian cancer. The most prolific contributors are Yung, Mingo M.H., Xiong, Ying, and Ngan, Hextany S., each publishing four articles (Table 2) (Fig. 5A). The three authors with the highest citation totals are Deik, Amy A., cited 995 times, Clish, Clary B., also cited 995 times, and Zou, Yilong, cited 987 times (Table 2) (Fig. 5B).
Table 2.
Top 10 authors by document numbers, citation numbers, and TLS numbers
| Top 10 authors | ||||||
|---|---|---|---|---|---|---|
| Rank | By documents numbers | By citation numbers | By TLS numbers | |||
| 1 | yung, mingo m.h. | 4 | deik, amy a. | 995 | clish, clary b. | 19 |
| 2 | xiong, ying | 4 | clish, clary b. | 995 | deik, amy a. | 19 |
| 3 | ngan, hextany.s. | 4 | zou, yilong | 987 | chan, david w. | 18 |
| 4 | liu, te | 4 | wang, wenyu | 987 | chan, karen k.I | 18 |
| 5 | liu, dan | 4 | schreiber, stuart L | 987 | ngan, hextan y.s. | 18 |
| 6 | chen, li | 4 | eaton, john k. | 987 | yung, mingo m.h. | 18 |
| 7 | chan, karen k.I | 4 | dancik, vlado | 987 | clemons, paul a. | 16 |
| 8 | chan, david w | 4 | clemons, paul a. | 987 | dancik, vlado | 16 |
| 9 | yang, wen-hsuan | 3 | weinberg, robert a | 444 | eaton, john k. | 16 |
| 10 | wang, yu | 3 | henry, whitney s. | 444 | schreiber, stuartl | 16 |
Fig. 5.
Analysis of authors. A Density visualization of 108 authors with more than two publications by document numbers. B Density visualization of 108 authors with more than two publications by citation numbers. C Density visualization of 108 authors with more than two publications by TLS numbers. D Network visualization of 108 authors with more than two publications by TLS numbers
There are 108 authors with more than two publications. The collaboration among these highly productive authors, highlighting the cooperation patterns in this field. The results indicate that tThe collaboration network formed by Clish, Clary B., Deik, Amy A., Eaton, John K., and others is the most cohesive. Yung, Mingo M.H., Chan, David W., Chan, Karen K.I., among others, also established a close collaborative network. However, there is a lack of connection between these two collaboration networks and limited ties with other collaborative groups (Table 2) (Fig. 5C-D).
Analysis of journals
A total of 153 journals contributed 237 articles on ferroptosis and ovarian cancer. The top three journals by publication volume are the International Journal of Molecular Sciences with 8 articles, Frontiers in Oncology with 7 articles, and Scientific Reports with 7 articles. The top three journals by citation count are Nature Communications with 551 citations, Cancer Research with 491 citations, and Nature with 436 citations. The publication and citation counts for these 153 journals can be displayed using density visualization (Table 3) (Fig. 6A-B). Subsequently, an overlay visualization shows that journals such as Nature, Redox Biology, and Nature Communications primarily published earlier (nodes in blue), while Aging-US, Apoptosis, and Clinical Cancer Research primarily published more recently (nodes in yellow) (Fig. 6C).
Table 3.
Top 10 journals by document numbers, and citation numbers
| Top 10 journals | ||||
|---|---|---|---|---|
| Rank | By documents numbers | By citations numbers | ||
| 1 | international journal of molecular sciences | 8 | nature communications | 551 |
| 2 | frontiers in oncology | 7 | cancer research | 491 |
| 3 | scientific reports | 7 | nature | 436 |
| 4 | journal of ovarian research | 6 | oncogene | 306 |
| 5 | frontiers in molecular biosciences | 6 | molecular cancer research | 266 |
| 6 | cancer research | 5 | redox biology | 217 |
| 7 | biomedicine &pharmacotherapy | 5 | frontiers in oncology | 193 |
| 8 | frontiers in genetics | 5 | cell metabolism | 174 |
| 9 | antioxidants | 4 | biomaterials | 160 |
| 10 | frontiers in pharmacology | 3 | molecular carcinogenesis | 140 |
Fig. 6.
Analysis of journals. A Density visualization of 153 journals by document numbers. B Density visualization of 153 journals by citation numbers. C The overlay visualization of bibliographic coupling among 153 journals
Analysis of references
Table 4 lists the top 10 most cited references in the research on ferroptosis and ovarian cancer. The three most frequently cited papers are: “CD8 + T cells regulate tumour ferroptosis during cancer immunotherapy” by Hong T et al. published in 2021 in REDOX BIOL [10], cited 43 times; “Frizzled-7 Identifies Platinum-Tolerant Ovarian Cancer Cells Susceptible to Ferroptosis” by Wang YN et al. published in 2021 in CANCER RES [9], cited 33 times; and Wang WM et al.‘s paper “CD8 + T cells regulate tumour ferroptosis during cancer immunotherapy” published in 2019 in NATURE [14], cited 32 times. Moreover, Citations from high-impact factor journals tend to have a longer Cited Half-life.
Table 4.
Top 10 cited references by citations
| Title | Journal | First author | Year | Total citation frequency | Half-life |
|---|---|---|---|---|---|
| PARP inhibition promotes ferroptosis via repressing SLC7A11 and synergizes with ferroptosis inducers in BRCA-proficient ovarian cancer | REDOX BIOL | Hong T | 2021 | 43 | 1.5 |
| Frizzled-7 Identifies Platinum-Tolerant Ovarian Cancer Cells Susceptible to Ferroptosis | CANCER RES | Wang YN | 2021 | 33 | 1.5 |
| CD8 + T cells regulate tumour ferroptosis during cancer immunotherapy | NATURE | Wang WM | 2019 | 32 | 3.5 |
| Targeting Ferroptosis to Iron Out Cancer | CANCER CELL | Hassannia B | 2019 | 31 | 3.5 |
| Ferroptosis: mechanisms, biology and role in disease | NAT REV MOL CELL BIO | Jiang XJ | 2021 | 31 | 2.5 |
| Stearoyl-CoA Desaturase 1 Protects Ovarian Cancer Cells from Ferroptotic Cell Death | CANCER RES | Tesfay L | 2019 | 30 | 2.5 |
| Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease | CELL | Stockwell BR | 2017 | 29 | 3.5 |
| The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis | NATURE | Bersuker K | 2019 | 27 | 3.5 |
| Epithelial ovarian cancer | LANCET | Lheureux S | 2019 | 27 | 3.5 |
| Gantenerumab reduces amyloid-β plaques Recent Progress in Ferroptosis Inducers for Cancer Therapy | ADV MATER | Liang C | 2019 | 26 | 3.5 |
The co-citation visualization analysis using CiteSpace categorized co-cited references into several groups, including prognostic model, ferroptotic cell death, mechanisms crosstalk, therapeutic strategies, ferroptosis-related gene, gene signature, systems biology, sensitivity marker, emerging therapeutic approaches, and non-coding RNA, totaling 10 clusters. The timeline view illustrates the evolution of co-cited references over time (Fig. 7A). Notably, papers related to ferroptotic cell death were more frequently cited before 2020. In contrast, references concerning emerging therapeutic approaches and non-coding RNA were more concentrated post-2020.
Fig. 7.
Analysis of journals references. A Timeline view of references clusters. B Bursts analysis of references
Burst analysis indicates that a total of nine citations have been detected to have experienced citation bursts. The paper “Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway” by Vasanthi S. Viswanathan et al. [15] published in 2017 in NATURE exhibited the highest citation burst intensity (strength = 8.67), while the longest citation burst duration was observed for the paper “Ferroptosis: Death by Lipid Peroxidation” by Wan Seok Yang et al. published in 2016 in TRENDS CELL BIOL [16], which lasted from 2018 to 2021 (Fig. 7B).
Analysis of keywords
Through co-occurrence analysis via VOSviewer, we identified a total of 1,103 keywords. We selected and analyzed all keywords that appeared at least five times across the papers, yielding 71 identified keywords (Fig. 8A). The top ten keywords by frequency are as follows: ferroptosis (Occurrences = 165, TLS = 628), ovarian cancer (Occurrences = 111, TLS = 399), cell death (Occurrences = 44, TLS = 229), apoptosis (Occurrences = 35, TLS = 187), expression (Occurrences = 35, TLS = 156), death (Occurrences = 34, TLS = 143), iron (Occurrences = 33, TLS = 185), resistance (Occurrences = 27, TLS = 166), metabolism (Occurrences = 25, TLS = 147), and cells (Occurrences = 25, TLS = 113) (Figs. 8B-C).
Fig. 8.
Analysis of keywords. (A) Network visualization of keywords by occurrences. (B) Density visualization of keywords by occurrences. (C) Top 10 institutions by occurrences. (D) Top 10 keywords by occurrence. (E) Timeline view of keyword clustering analysis
Burst analysis of keywords demonstrates that ‘in vitro’ has the highest burst strength (strength = 4.15), while ‘biology’ has the longest duration of burst, occurring from 2017 to 2020 (Fig. 8D). Additionally, through clustering analysis of keywords with Citespace and displaying the results in a timeline view, we categorized keywords into 13 clusters: sensitivity marker, clinical outcome, inhibiting cell cycle, cacna1g-as1 up-regulate, reversing multidrug resistance, novel landscape, ovarian cancer cell growth arrest, female-specific neoplasm, 4ebp1-mediated slc7a11 protein synthesis, genomic landscape analysis, cancer cell, metabolism-related Incrna, and pml-regulated mitochondrial metabolism. Among these clusters, genomic landscape analysis and metabolism-related Incrna keywords primarily emerged in recent years, while keywords from the other clusters appeared earlier and remain prevalent (Fig. 8E).
Text mining
Using CoreMine Medical platform for text mining revealed that cisplatin, SLC7A11, and GPX4 significantly correlate with both ovarian cancer and ferroptosis. Specifically, cisplatin has 10,892 articles related to ovarian cancer (P = 3.33E-06) and 322 articles related to ferroptosis (P = 4.97E-04). SLC7A11 connects with ovarian cancer in 43 articles (P = 6.89E-03) and with ferroptosis in 1,489 articles (P = 4.03E-07). GPX4 appears in 44 articles about ovarian cancer (P = 1.71E-02) and in 3,180 articles about ferroptosis (P = 1.56E-07) (Fig. 9). This suggests that the drugs and genes mentioned likely influence the relationship between ferroptosis and ovarian cancer.
Fig. 9.
Text mining analysis using coremine
Discussion
Principal findings
Research on ovarian cancer and ferroptosis has increased significantly. The interests and directions of these studies are diverse. Understanding the key focuses and hotspots is a major concern for researchers in this field. Unlike reviews, bibliometric methods analyze objective literature data to calculate the relevant research metrics in ovarian cancer and ferroptosis. This paper conducts the first bibliometric analysis in this area, providing researchers with insights into research priorities, emerging trends, and existing issues.
Ferroptosis was first proposed by Brent R. Stockwell in 2012 [17]. In 2013, a link was reported between ferroptosis and liver cancer [18]. By 2014, associations emerged between ferroptosis and diffuse large B cell lymphomas, as well as renal cell carcinomas [19]. However, it was not until 2017 that research articles addressing ferroptosis and ovarian cancer were published [20, 21]. Before 2020, the output of related studies remained low. Therefore, the investigation of ferroptosis in ovarian cancer began relatively late. Nonetheless, after 2022, the volume of publications in this field surged, reaching 73 articles by 2023. The fitting curve also indicates a continued increase. This trend highlights the growing significance of ferroptosis in ovarian cancer and reflects a notable rise in interest among researchers regarding this topic.
China and the United States undeniably stand at the forefront of academic publishing in the realms of iron death and ovarian cancer research. These two nations significantly overshadow other countries when considering both the sheer number of published articles and the corresponding citation metrics. In addition to this dominance, they engage in the most extensive research partnerships, reinforcing their pivotal positions in shaping the trajectory of advancements in these specialized fields. This assertion gains further credibility when we delve into institutional data regarding publication and citation output. Interestingly, while Japan and Canada do not hold the top spots for article publication, they nonetheless made groundbreaking contributions during the early stages of research within this area, and their citation records remain remarkably high. Their historical significance cannot be overlooked, even as their publication volumes may appear less formidable.
Upon a meticulous examination of institutional output, it becomes apparent that leading publishing institutions predominantly stem from China. Conversely, the highest citation counts are primarily attributed to numerous esteemed institutions in the United States. This pronounced discrepancy between publication counts and citation metrics warrants significant attention. It implies that while there exists a robust framework for collaboration between China and the United States, there remains a notable gap in shared efforts toward innovative research initiatives. This factor could hinder the potential for groundbreaking discoveries and advancements in tackling both iron death and ovarian cancer. Additionally, there exist a discernible lack of interconnectivity between the two prominent author collaboration networks in our authorship analysis. Our analysis emphasizes the nature of collaboration in the ongoing exploration of ferroptosis and ovarian cancer, revealing both robust partnerships and areas where connections could be enhanced. Thus, a strategic focus on fostering comprehensive collaborative endeavours could enhance the research outcomes in these critical health domains.
The timeline view effectively demonstrates the temporal dynamics of co-cited literature, illustrating how citation trends have evolved over time. Notably, academic citations focusing on ferroptosis mechanisms exhibited a higher frequency prior to 2020. In contrast, literature concentrating on emerging therapeutic strategies and the role of non-coding RNA witnessed an increase in citation density after 2020. This trend indicates a growing interest among researchers in exploring the relationship between ferroptosis and ovarian cancer, particularly through new therapeutic approaches and non-coding RNA, marking it as a burgeoning research frontier. Furthermore, keyword analysis revealed that metabolism-related Incrna keywords have gained prominence in recent years, highlighting the significant role of Incrna in ferroptosis within ovarian cancer. Studies indicate that specific lncRNA transcripts can regulate the ferroptosis process by directly modulating key factors or indirectly influencing molecular targets located upstream of this mechanism [22]. Additionally, analysis of public databases revealed that eleven ferroptosis-associated lncRNAs effectively prognosticated the outcomes of ovarian cancer patients [23]. Analysis using OC specimens and cell lines found that long non-coding RNA TPT1-AS1 inhibits ferroptosis in ovarian cancer by modulating GPX4 through the regulation of CREB1 [24].
Long non-coding RNAs provide numerous therapeutic advantages. non-coding RNAs are endogenous cellular components capable of modulating interconnected metabolic pathways, enabling multi-gene targeting for enhanced anticancer efficacy.The miR-15–miR-16 cluster exemplifies this by concurrently regulating proteins involved in apoptosis and cell cycle control [25]. Furthermore, long non-coding RNAs frequently target multiple genes and interrelated pathways, resulting in broad yet specific anti-cancer responses. A noteworthy example is the MIR15-MIR16 complex, which regulates several anti-apoptotic and cell cycle proteins [26]. Critically, multiple RNA-targeted therapeutics have been developed, including antisense oligonucleotides (ASOs), antisense circRNAs, anti-microRNA oligos (anti-miRs), siRNAs, microRNA sponges and mimics, shRNAs, and CRISPR-Cas9 genome editing systems [27]. Ultimately, non-coding RNA therapies hold the promise of cost-effective production through chemical synthesis [28]. However, non-coding RNA-based ferroptosis treatments encounter potential limitations. First, the influence of non-coding RNAs on tumorigenesis may exhibit inconsistent efficacy across heterogeneous tumor microenvironments, particularly when targeting complex ferroptosis regulatory networks [29]. Second, substantial variability in individual non-coding RNA expression profiles across patient populations, combined with diverse cellular responses to exogenous RNA interventions, complicates the predictability of treatment outcomes and poses challenges for standardized therapeutic protocols [27]. Lastly, achieving an equilibrium between promoting ferroptosis to inhibit tumors and utilizing non-coding RNAs to counteract chemotherapy resistance remains biologically complex, demanding further mechanistic investigation into temporal and spatial regulation of these dual processes [30]. Therefore, additional research is crucial to assess the clinical potential of targeting ferroptosis-associated non-coding RNAs.
The primary characteristics of ferroptosis involve iron accumulation and lipid peroxidation. Previous studies indicate that chemotherapy-resistant tumor cells exhibit particular sensitivity to lipid peroxidation [31]. Therefore, activating ferroptosis-related therapeutic targets in ovarian cancer and inducing lipid peroxidation in ovarian cancer cells may represent a potential pharmacological approach to overcome chemotherapy resistance. In our keyword analysis, we found that “resistance” is among the top ten frequently occurring keywords. Cluster analysis revealed one cluster focused on reversing multidrug resistance. Coremine text mining analysis showed that cisplatin is significantly associated with both ferroptosis and ovarian cancer. These results highlight that reversing chemotherapy resistance through ferroptosis is a key concern for researchers and a hot topic of study. The efficacy of compounds such as NL01, triptolide, and nitrosyl iron in promoting ferroptosis unveils promising therapeutic avenues [32]. These agents concurrently confront resistance mechanisms and dismantle essential survival pathways in ovarian cancer cells. Nevertheless, the possible adverse effects of these ferroptosis-inducing agents, along with the applicability of the results, demand meticulous scrutiny, especially since numerous treatment modalities are still in preliminary phases. Consequently, future investigations must delve deeper into strategies for surmounting ovarian cancer resistance through ferroptosis, as well as translating these findings into clinical applications, evaluating them against current therapies, and examining wider ramifications for other malignancies.
Limitations
This paper’s bibliometric section only retrieves data from the WOS database regarding ferroptosis and ovarian cancer, excluding other databases and literature research in languages other than English, such as the Chinese database CNKI. This approach may underrepresent contributions from non-English speaking regions and affect the generalizability of global research trends. The Coremine text mining results also include only MEDLINE, which inevitably leads to gaps in relevant literature and may result in the loss of some important clues. Consequently, findings on regional collaborations and emerging topics could be biased toward Anglophone contexts. Additionally, the literature statistics for 2024 await completion of the year, making it impossible to obtain an accurate annual publication and citation volume.
Conclusions
In summary, our article primarily reveals the publication trends, collaborations among countries, regions, and authors, as well as recent research hotspots in the study of the correlation between ferroptosis and ovarian cancer, through bibliometric methods combined with text mining techniques. We provide objective data to reference the scientific research and clinical work regarding ferroptosis and ovarian cancer. To further advance this field, future research could explore under-researched areas such as the role of ferroptosis in different subtypes of ovarian cancer or the development of ferroptosis-based therapeutic strategies, which would enhance the translational value of current findings.
Author contributions
Dingwen Xu designed and organized the study. Hongwang Yuan conduct analysis used VOSviewer and wrote this manuscript., Zhanyan Hua and Hua Zhang conduct analysis used CiteSpace and Coremine.
Funding
None.
Data availability
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Hongwang Yuan and Zhanyan Hua are co-first authors.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.