Trends and hotspots in lung cancer liquid biopsy research: A bibliometric analysis_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

TIAN Zhenni ¹ , NING Yeping ¹ , FENG Xiaomeng ¹ , WANG Jin ¹ ,  LEI Fengfeng ^1,2

1. The First Clinical Medical College of Gansu University of Traditional Chinese Medicine, Lanzhou, 730000, P. R. China;
2. Department of Respiratory and Critical Care Medicine, Gansu Provincial People’s Hospital, Lanzhou, 730000, P. R. China;

Corresponding author：

LEI Fengfeng, Email: leifengfenglf@163.com

Keywords：

Lung cancer; liquid biopsy; bibliometrics; visualization

DOI：

10.7507/1007-4848.202508003

Video：

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Objective To explore the present state of research, emerging trends, and key topics in the field of liquid biopsy for lung cancer, offering insights for the holistic management of the disease. Methods Data was sourced from the Web of Science Core Collection database, focusing on literature related to liquid biopsy in lung cancer published between 2012 and 2025. Tools such as CiteSpace and Biblioshiny were employed to perform a detailed visual analysis of various aspects, including publication outputs, contributing countries and institutions, international collaborations, leading authors, prominent journals, academic disciplines, keyword distributions, and cited references. Results A total of 1 128 articles were analyzed. Findings indicated that research in the area of liquid biopsy for lung cancer experienced rapid growth since 2014, peaking in 2022. The majority of research efforts were centered in China and the United States. The French institution Institut National de la Sante et de la Recherche Medicale (INSERM) leaded in publication output. Malapelle U was the most prolific author. The journal Cancers published the highest number of related articles. Keywords analysis highlighted liquid biopsy and lung cancer as central research themes. Key research topics consistently included circulating tumor DNA, circulating tumor cells, extracellular vesicles, epidermal growth factor receptor mutations, and DNA methylation in the context of liquid biopsy. Meanwhile, immunotherapy and minimal residual disease emerged as frontier areas in this domain. Conclusion The bibliometric results demonstrate a continuous rise in scholarly output on liquid biopsy in lung cancer. The identified research hotspots and evolving trends offer valuable guidance for future studies, with the ultimate goal of facilitating broader clinical adoption of liquid biopsy technologies and advancing precision medicine in lung cancer treatment.

1.	Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024, 74(3): 229-263.
2.	Kratezr TB, Band P, Freedman ND, et al. Lung cancer statistics, 2023. Cancer, 2024, 130(8): 1330-1348.
3.	Heitezr E, Haque IS, Roberts CES, et al. Current and future perspectives of liquid biopsies in genomics-driven oncology. Nat Rev Genet, 2019, 20(2): 71-88.
4.	Maggio LA, Leroux TC, Meyer HS, et al. #MedEd: exploring the relationship between altmetrics and traditional measures of dissemination in health professions education. Perspect Med Educ, 2018, 7(4): 239-247.
5.	Chen CM, Leydesdorff L. Patterns of connections and movements in dual-map overlays: a new method of publication portfolio analysis. J Assoc Inf Sci Technol, 2014, 65(2): 334-351.
6.	Ai S, Li Y, Tao J, et al. Bibliometric visualization analysis of gut-kidney axis from 2003 to 2022. Front Physiol, 2023, 14: 1176894.
7.	Abu RF, Singhi EK, Sridhar A, et al. Lung cancer treatment advances in 2022. Cancer Invest, 2023, 41(1): 12-24.
8.	Ghani MU, Du L, Moqbel AQ, et al. Exosomal ncRNAs in liquid biopsy: a new paradigm for early cancer diagnosis and monitoring. Front Oncol, 2025, 15: 1615433.
9.	Dao J, Conway PJ, Subramani B, et al. Using cfDNA and ctDNA as oncologic markers: a path to clinical validation. Int J Mol Sci, 2023, 24(17): 13258.
10.	Harrison PT, Vyse S, Huang PH. Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer. Semin Cancer Biol, 2020, 61: 167-179.
11.	Klein EA, Richards D, Cohn A, et al. Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set. Ann Oncol, 2021, 32(9): 1167-1177.
12.	Romero A, Serna-Blasco R, Alfaro C, et al. ctDNA analysis reveals different molecular patterns upon disease progression in patients treated with osimertinib. Transl Lung Cancer Res, 2020, 9(3): 532-540.
13.	Zhang C, Wei B, Li P, et al. Prognostic value of plasma EGFR ctDNA in NSCLC patients treated with EGFR-TKIs. PLoS One, 2017, 12(3): e0173524.
14.	Chen Y, Peng S, Wang C. The advances of DNA methylation in the liquid biopsy for the detection of lung cancer. Front Oncol, 2025, 15: 1547797.
15.	Myrkhiyeva Z, Seitkamal K, Ashikbayeva Z, et al. Circulating tumor cells: overcoming challenges of detecting a needle in a haystack. Explor Target Antitumor Ther, 2025, 6: 1002321.
16.	Pfarr N, Penzel R, Klauschen F, et al. Copy number changes of clinically actionable genes in melanoma, non-small cell lung cancer and colorectal cancer-a survey across 822 routine diagnostic cases. Genes Chromosomes Cancer, 2016, 55(11): 821-833.
17.	Xu Y, Hu X, Yuan Y, et al. Prediction of lung cancer metastasis risk based on single-cell metabolic profiling of circulating tumor cells. Adv Sci (Weinh), 2025: e2408878.
18.	Fusco C, De RG, Spatocco I, et al. Extracellular vesicles as human therapeutics: a scoping review of the literature. J Extracell Vesicles, 2024, 13(5): e12433.
19.	Zhou Z, Qu C, Zhou P, et al. Extracellular vesicles activated cancer-associated fibroblasts promote lung cancer metastasis through mitophagy and mtDNA transfer. J Exp Clin Cancer Res, 2024, 43(1): 158.
20.	Mamdani H, Matosevic S, Khalid AB, et al. Immunotherapy in lung cancer: current landscape and future directions. Front Immunol, 2022, 13: 823618.
21.	Boscolo BA, Del BP, Zulato E, et al. Longitudinal liquid biopsy predicts clinical benefit from immunotherapy in advanced non-small cell lung cancer. NPJ Precis Oncol, 2024, 8(1): 234.
22.	Assaf ZJF, Zou W, Fine AD, et al. A longitudinal circulating tumor DNA-based model associated with survival in metastatic non-small-cell lung cancer. Nat Med, 2023, 29(4): 859-868.
23.	Purcell E, Niu Z, Owen S, et al. Circulating tumor cells reveal early predictors of disease progression in patients with stage III NSCLC undergoing chemoradiation and immunotherapy. Cell Rep, 2024, 43(2): 113687.
24.	Peng XX, Yu R, Wu X, et al. Correlation of plasma exosomal microRNAs with the efficacy of immunotherapy in EGFR/ALK wild-type advanced non-small cell lung cancer. J Immunother Cancer, 2020, 8(1): e000376.
25.	Del RM, Marconcini R, Pasquini G, et al. PD-L1 mRNA expression in plasma-derived exosomes is associated with response to anti-PD-1 antibodies in melanoma and NSCLC. Br J Cancer, 2018, 118(6): 820-824.
26.	Murray NP. Biomarkers of minimal residual disease and treatment. Adv Clin Chem, 2024, 119: 33-70.
27.	Moding EJ, Liu Y, Nabet BY, et al. Circulating tumor DNA dynamics predict benefit from consolidation immunotherapy in locally advanced non-small cell lung cancer. Nat Cancer, 2020, 1(2): 176-183.
28.	Peters S, Spigel D, Ahn M, et al. MERMAID-1: a phase III study of adjuvant durvalumab plus chemotherapy in resected NSCLC patients with MRD plus post-surgery. J Thorac Oncol, 2021, 16(3): S258-S259.
29.	Herbst RS, John T, Grohé C, et al. Molecular residual disease analysis of adjuvant osimertinib in resected EGFR-mutated stage IB-IIIA non-small-cell lung cancer. Nat Med, 2025, 31(6): 1958-1968.
30.	Mori T, Kitagawa M, Hasegawa T, et al. Autoantibody spark response predicts treatment outcome in patients receiving chemoradiation followed by durvalumab therapy. Sci Rep, 2025, 15(1): 27502.

1. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024, 74(3): 229-263.
2. Kratezr TB, Band P, Freedman ND, et al. Lung cancer statistics, 2023. Cancer, 2024, 130(8): 1330-1348.
3. Heitezr E, Haque IS, Roberts CES, et al. Current and future perspectives of liquid biopsies in genomics-driven oncology. Nat Rev Genet, 2019, 20(2): 71-88.
4. Maggio LA, Leroux TC, Meyer HS, et al. #MedEd: exploring the relationship between altmetrics and traditional measures of dissemination in health professions education. Perspect Med Educ, 2018, 7(4): 239-247.
5. Chen CM, Leydesdorff L. Patterns of connections and movements in dual-map overlays: a new method of publication portfolio analysis. J Assoc Inf Sci Technol, 2014, 65(2): 334-351.
6. Ai S, Li Y, Tao J, et al. Bibliometric visualization analysis of gut-kidney axis from 2003 to 2022. Front Physiol, 2023, 14: 1176894.
7. Abu RF, Singhi EK, Sridhar A, et al. Lung cancer treatment advances in 2022. Cancer Invest, 2023, 41(1): 12-24.
8. Ghani MU, Du L, Moqbel AQ, et al. Exosomal ncRNAs in liquid biopsy: a new paradigm for early cancer diagnosis and monitoring. Front Oncol, 2025, 15: 1615433.
9. Dao J, Conway PJ, Subramani B, et al. Using cfDNA and ctDNA as oncologic markers: a path to clinical validation. Int J Mol Sci, 2023, 24(17): 13258.
10. Harrison PT, Vyse S, Huang PH. Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer. Semin Cancer Biol, 2020, 61: 167-179.
11. Klein EA, Richards D, Cohn A, et al. Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set. Ann Oncol, 2021, 32(9): 1167-1177.
12. Romero A, Serna-Blasco R, Alfaro C, et al. ctDNA analysis reveals different molecular patterns upon disease progression in patients treated with osimertinib. Transl Lung Cancer Res, 2020, 9(3): 532-540.
13. Zhang C, Wei B, Li P, et al. Prognostic value of plasma EGFR ctDNA in NSCLC patients treated with EGFR-TKIs. PLoS One, 2017, 12(3): e0173524.
14. Chen Y, Peng S, Wang C. The advances of DNA methylation in the liquid biopsy for the detection of lung cancer. Front Oncol, 2025, 15: 1547797.
15. Myrkhiyeva Z, Seitkamal K, Ashikbayeva Z, et al. Circulating tumor cells: overcoming challenges of detecting a needle in a haystack. Explor Target Antitumor Ther, 2025, 6: 1002321.
16. Pfarr N, Penzel R, Klauschen F, et al. Copy number changes of clinically actionable genes in melanoma, non-small cell lung cancer and colorectal cancer-a survey across 822 routine diagnostic cases. Genes Chromosomes Cancer, 2016, 55(11): 821-833.
17. Xu Y, Hu X, Yuan Y, et al. Prediction of lung cancer metastasis risk based on single-cell metabolic profiling of circulating tumor cells. Adv Sci (Weinh), 2025: e2408878.
18. Fusco C, De RG, Spatocco I, et al. Extracellular vesicles as human therapeutics: a scoping review of the literature. J Extracell Vesicles, 2024, 13(5): e12433.
19. Zhou Z, Qu C, Zhou P, et al. Extracellular vesicles activated cancer-associated fibroblasts promote lung cancer metastasis through mitophagy and mtDNA transfer. J Exp Clin Cancer Res, 2024, 43(1): 158.
20. Mamdani H, Matosevic S, Khalid AB, et al. Immunotherapy in lung cancer: current landscape and future directions. Front Immunol, 2022, 13: 823618.
21. Boscolo BA, Del BP, Zulato E, et al. Longitudinal liquid biopsy predicts clinical benefit from immunotherapy in advanced non-small cell lung cancer. NPJ Precis Oncol, 2024, 8(1): 234.
22. Assaf ZJF, Zou W, Fine AD, et al. A longitudinal circulating tumor DNA-based model associated with survival in metastatic non-small-cell lung cancer. Nat Med, 2023, 29(4): 859-868.
23. Purcell E, Niu Z, Owen S, et al. Circulating tumor cells reveal early predictors of disease progression in patients with stage III NSCLC undergoing chemoradiation and immunotherapy. Cell Rep, 2024, 43(2): 113687.
24. Peng XX, Yu R, Wu X, et al. Correlation of plasma exosomal microRNAs with the efficacy of immunotherapy in EGFR/ALK wild-type advanced non-small cell lung cancer. J Immunother Cancer, 2020, 8(1): e000376.
25. Del RM, Marconcini R, Pasquini G, et al. PD-L1 mRNA expression in plasma-derived exosomes is associated with response to anti-PD-1 antibodies in melanoma and NSCLC. Br J Cancer, 2018, 118(6): 820-824.
26. Murray NP. Biomarkers of minimal residual disease and treatment. Adv Clin Chem, 2024, 119: 33-70.
27. Moding EJ, Liu Y, Nabet BY, et al. Circulating tumor DNA dynamics predict benefit from consolidation immunotherapy in locally advanced non-small cell lung cancer. Nat Cancer, 2020, 1(2): 176-183.
28. Peters S, Spigel D, Ahn M, et al. MERMAID-1: a phase III study of adjuvant durvalumab plus chemotherapy in resected NSCLC patients with MRD plus post-surgery. J Thorac Oncol, 2021, 16(3): S258-S259.
29. Herbst RS, John T, Grohé C, et al. Molecular residual disease analysis of adjuvant osimertinib in resected EGFR-mutated stage IB-IIIA non-small-cell lung cancer. Nat Med, 2025, 31(6): 1958-1968.
30. Mori T, Kitagawa M, Hasegawa T, et al. Autoantibody spark response predicts treatment outcome in patients receiving chemoradiation followed by durvalumab therapy. Sci Rep, 2025, 15(1): 27502.

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