Progress in the application of exosomes in liquid biopsy for early diagnosis and screening of lung cancer_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

LIU Zelin ^1,2 , SUN Shixiang ^2,3 ,  ZHAO Jinlong ²

1. The Second Clinical Medical College, Binzhou Medical University, Yantai, 264003, Shandong, P. R. China;
2. Department of Thoracic Surgery, Linyi People's Hospital of Shandong Province, Linyi, 276003, Shandong, P. R. China;
3. Clinical Medical College, Shandong Second Medical University, Weifang, 261053, Shandong, P. R. China;

Corresponding?author：

ZHAO Jinlong, Email: zhaojinlong-125@163.com

Keywords：

Lung cancer; liquid biopsy; exosomes; biomarkers; early diagnosis; multi-omics technologies; artificial intelligence; clinical applications

DOI：

10.7507/1007-4848.202512031

Video：

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Abstract Full text Figures/Tables Video References Cited by

Lung cancer is the malignant tumor with the highest incidence and mortality rates worldwide, and its high lethality is primarily due to its subtle early symptoms, with most cases being diagnosed at an advanced stage. Currently, the diagnosis of lung cancer mainly relies on tissue biopsy to obtain pathological evidence, but this method has limitations such as high invasiveness, restricted sampling, and the risk of complications. Therefore, developing safe, effective, and non-invasive strategies for the early screening and diagnosis of lung cancer (stages Ⅰ/Ⅱ) holds significant clinical importance. As a key component of liquid biopsy, exosomes can stably carry a variety of biological molecular information from their cells of origin. Studies have shown that microRNAs, long non-coding RNAs, circular RNAs, and specific proteins abundantly present in exosomes exhibit abnormal expression during the development of lung cancer, demonstrating high diagnostic value. Compared to traditional detection methods, exosome-based detection offers advantages such as non-invasiveness, repeatability, ease of operation, and cost-effectiveness. This article systematically reviews recent research progress on exosomes as liquid biopsy biomarkers for the early diagnosis and screening of lung cancer, focusing on their potential clinical applications, and explores the prospects of exsomes in the early intervention, precise diagnosis, and prognosis improvement for lung cancer.

1.	Leiter A, Veluswamy RR, Wisnivesky JP. The global burden of lung cancer: current status and future trends. Nat Rev Clin Oncol, 2023, 20(9): 624-639.
2.	Feng R, Su Q, Huang X, et al. Cancer situation in China: what does the China cancer map indicate from the first national death survey to the latest cancer registration? Cancer Commun (Lond), 2023, 43(1): 75-86.
3.	Giaccone G, He Y. Current knowledge of small cell lung cancer transformation from non-small cell lung cancer. Semin Cancer Biol, 2023, 94: 1-10.
4.	Galetta D. Advances in lung cancer therapy. Cancers (Basel), 2023, 15(10): 2671.
5.	Shimizu K, Ohtaki Y, Suzuki K, et al. Salvage surgery for non-small cell lung cancer after definitive radiotherapy. Ann Thorac Surg, 2021, 112(3): 862-873.
6.	Wang Y, Li C, Wang Z, et al. Comparison between immunotherapy efficacy in early non-small cell lung cancer and advanced non-small cell lung cancer: a systematic review. BMC Med, 2022, 20(1): 426.
7.	Bodor JN, Boumber Y, Borghaei H. Biomarkers for immune checkpoint inhibition in non-small cell lung cancer (NSCLC). Cancer, 2020, 126(2): 260-270.
8.	Zhou B, Xu K, Zheng X, et al. Application of exosomes as liquid biopsy in clinical diagnosis. Signal Transduct Target Ther, 2020, 5(1): 144.
9.	Shen H, Jin Y, Zhao H, et al. Potential clinical utility of liquid biopsy in early-stage non-small cell lung cancer. BMC Med, 2022, 20(1): 480.
10.	Li W, Liu JB, Hou LK, et al. Liquid biopsy in lung cancer: significance in diagnostics, prediction, and treatment monitoring. Mol Cancer, 2022, 21(1): 25.
11.	Ren F, Fei Q, Qiu K, et al. Liquid biopsy techniques and lung cancer: diagnosis, monitoring and evaluation. J Exp Clin Cancer Res, 2024, 43(1): 96.
12.	Siravegna G, Mussolin B, Venesio T, et al. How liquid biopsies can change clinical practice in oncology. Ann Oncol, 2019, 30(10): 1580-1590.
13.	Ignatiadis M, Sledge GW, Jeffrey SS. Liquid biopsy enters the clinic-implementation issues and future challenges. Nat Rev Clin Oncol, 2021, 18(5): 297-312.
14.	Connal S, Cameron JM, Sala A, et al. Liquid biopsies: the future of cancer early detection. J Transl Med, 2023, 21(1): 118.
15.	Tarasov VV, Svistunov AA, Chubarev VN, et al. Extracellular vesicles in cancer nanomedicine. Semin Cancer Biol, 2021, 69: 212-225.
16.	Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science, 2020, 367(6478): eaau6977.
17.	Sadik N, Cruz L, Gurtner A, et al. Extracellular RNAs: a new awareness of old perspectives. Methods Mol Biol, 2018, 1740: 1-15.
18.	Zhao L, Wang H, Fu J, et al. Microfluidic-based exosome isolation and highly sensitive aptamer exosome membrane protein detection for lung cancer diagnosis. Biosens Bioelectron, 2022, 214: 114487.
19.	Zhang X, Xu Y, Ma L, et al. Essential roles of exosome and circRNA_101093 on ferroptosis desensitization in lung adenocarcinoma. Cancer Commun (Lond), 2022, 42(4): 287-313.
20.	Shang R, Lee S, Senavirathne G, et al. microRNAs in action: biogenesis, function and regulation. Nat Rev Genet, 2023, 24(12): 816-833.
21.	Li C, Zhou T, Chen J, et al. The role of exosomal miRNAs in cancer. J Transl Med, 2022, 20(1): 6.
22.	Kim DH, Park H, Choi YJ, et al. Identification of exosomal microRNA panel as diagnostic and prognostic biomarker for small cell lung cancer. Biomark Res, 2023, 11(1): 80.
23.	Zhang Q, Zheng K, Gao Y, et al. Plasma exosomal miR-1290 and miR-29c-3p as diagnostic biomarkers for lung cancer. Heliyon, 2023, 9(10): e21059.
24.	Zheng B, Peng M, Gong J, et al. Circulating exosomal microRNA-4497 as a potential biomarker for metastasis and prognosis in non-small-cell lung cancer. Exp Biol Med (Maywood), 2023, 248(16): 1403-1413.
25.	Zhang Z, Tang Y, Song X, et al. Tumor-derived exosomal miRNAs as diagnostic biomarkers in non-small cell lung cancer. Front Oncol, 2020, 10: 560025.
26.	Hassanin AAI, Ramos KS. Circulating exosomal miRNA profiles in non-small cell lung cancers. Cells, 2024, 13(18): 1562.
27.	Lu S, Kato T, Dong X, et al. Osimertinib after chemoradiotherapy in stage Ⅲ EGFR-mutated NSCLC. N Engl J Med, 2024, 391(7): 585-597.
28.	Padinharayil H, Varghese J, John MC, et al. Non-small cell lung carcinoma (NSCLC): implications on molecular pathology and advances in early diagnostics and therapeutics. Genes Dis, 2023, 10(3): 960-989.
29.	李紀遠, 馬新, 張燦斌, 等. 血清外泌體miR-20b-5p miR-107水平檢測在非小細胞肺腺癌診斷及預后評估中的應用. 安徽醫學, 2023, 44(1): 38-44.Li JY, Ma X, Zhang CB, et al. Application of serum exosomal miR-20b-5p and miR-107 in diagnosis and prognosis evaluation of non-small cell lung adenocarcinoma. Anhui Med J, 2023, 44(1): 38-44.
30.	Mu X, Yu C, Zhao Y, et al. Exosomal miR-1228-5p down-regulates DUSP22 to promotes cell proliferation and migration in small cell lung cancer. Life Sci, 2024, 351: 122787.
31.	Wang Z, Yang B, Zhang M, et al. LncRNA epigenetic landscape analysis identifies EPIC1 as an oncogenic lncRNA that interacts with MYC and promotes cell-cycle progression in cancer. Cancer Cell, 2018, 33(4): 706-720. e9.
32.	Li C, Lv Y, Shao C, et al. Tumor-derived exosomal lncRNA GAS5 as a biomarker for early-stage non-small-cell lung cancer diagnosis. J Cell Physiol, 2019, 234(11): 20721-20727.
33.	Xiong D, Wang C, Yang Z, et al. Clinical significance of serum-derived exosomal LINC00917 in patients with non-small cell lung cancer. Front Genet, 2021, 12: 728763.
34.	Tao Y, Tang Y, Yang Z, et al. Exploration of serum exosomal LncRNA TBILA and AGAP2-AS1 as promising biomarkers for diagnosis of non-small cell lung cancer. Int J Biol Sci, 2020, 16(3): 471-482.
35.	Zhang C, Xu L, Deng G, et al. Exosomal HOTAIR promotes proliferation, migration and invasion of lung cancer by sponging miR-203. Sci China Life Sci, 2020, 63(8): 1265-1268.
36.	Chen L, Huang S, Huang J, et al. Role and mechanism of exosome-derived long noncoding RNA HOTAIR in lung cancer. ACS Omega, 2021, 6(27): 17217-17227.
37.	Xian J, Zeng Y, Chen S, et al. Discovery of a novel linc01125 isoform in serum exosomes as a promising biomarker for NSCLC diagnosis and survival assessment. Carcinogenesis, 2021, 42(6): 831-841.
38.	Min L, Zhu T, Lv B, et al. Exosomal lncRNA RP5-977B1 as a novel minimally invasive biomarker for diagnosis and prognosis in non-small cell lung cancer. Int J Clin Oncol, 2022, 27(6): 1013-1024.
39.	Ma X, Chen Z, Chen W, et al. LncRNA AL139294.1 can be transported by extracellular vesicles to promote the oncogenic behaviour of recipient cells through activation of the Wnt and NF-κB2 pathways in non-small-cell lung cancer. J Exp Clin Cancer Res, 2024, 43(1): 20.
40.	Wang L, Xie Y, Wang J, et al. Characterization of a novel LUCAT1/miR-4316/VEGF-A axis in metastasis and glycolysis of lung adenocarcinoma. Front Cell Dev Biol, 2022, 10: 833579.
41.	Song X, Duan L, Dong Y. Diagnostic accuracy of exosomal long noncoding RNAs in diagnosis of NSCLC: a meta-analysis. Mol Diagn Ther, 2024, 28(4): 455-468.
42.	Wang MC, Gong GY, Wang CL, et al. Methods for collection of extracellular vesicles and their content RNA as liquid biopsy for lung cancer detection: application of differential centrifugation and annexin A5 coated beads. Curr Issues Mol Biol, 2022, 44(5): 2374-2386.
43.	Kang Y, You J, Gan Y, et al. Serum and serum exosomal circRNAs hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896 as diagnostic biomarkers for lung adenocarcinoma. Front Oncol, 2022, 12: 912246.
44.	Zhou H, Huang X, Yang X, et al. CircRAPGEF5 promotes the proliferation and metastasis of lung adenocarcinoma through the miR-1236-3p/ZEB1 axis and serves as a potential biomarker. Int J Biol Sci, 2022, 18(5): 2116-2131.
45.	He Y, Liu Y, Cha N, et al. Exosomal circ_0048856 derived from non-small cell lung cancer contributes to aggressive cancer progression through downregulation of miR-1287-5p. Pathol Res Pract, 2022, 232: 153659.
46.	Huang Y, Qin S, Gu X, et al. Comprehensive assessment of serum hsa_circ_0070354 as a novel diagnostic and predictive biomarker in non-small cell lung cancer. Front Genet, 2021, 12: 796776.
47.	Xian J, Su W, Liu L, et al. Identification of three circular RNA cargoes in serum exosomes as diagnostic biomarkers of non-small-cell lung cancer in the Chinese population. J Mol Diagn, 2020, 22(8): 1096-1108.
48.	Chen Y, Lou C, Ma X, et al. Serum exosomal hsa_circ_0069313 has a potential to diagnose more aggressive non-small cell lung cancer. Clin Biochem, 2022, 102: 56-64.
49.	Zhou T, Ma H, Li Z, et al. Exosomes in lung cancer: a role in early diagnosis. Front Oncol, 2025, 15: 1599608.
50.	Yoneyama T, Gorry M, Sobo-Vujanovic A, et al. ADAM10 sheddase activity is a potential lung-cancer biomarker. J Cancer, 2018, 9(14): 2559-2570.
51.	Ma Y, Marinkova R, Nenkov M, et al. Tumor-intrinsic PD-L1 exerts an oncogenic function through the activation of the Wnt/β-catenin pathway in human non-small cell lung cancer. Int J Mol Sci, 2022, 23(19): 11031.
52.	Li C, Li C, Zhi C, et al. Clinical significance of PD-L1 expression in serum-derived exosomes in NSCLC patients. J Transl Med, 2019, 17(1): 355.
53.	Zhang Z, Jin W, Xu K, et al. Blood exosome PD-L1 is associated with PD-L1 expression measured by immunohistochemistry, and lymph node metastasis in lung cancer. Tissue Cell, 2022, 79: 101941.
54.	Choi ES, Faruque HA, Kim JH, et al. CD5L as an extracellular vesicle-derived biomarker for liquid biopsy of lung cancer. Diagnostics (Basel), 2021, 11(4): 620.
55.	Jeong H, Choi BH, Park J, et al. GCC2 as a new early diagnostic biomarker for non-small cell lung cancer. Cancers (Basel), 2021, 13(21): 5482.
56.	Jin S, Liu T, Wang W, et al. Lymphocyte migration regulation related proteins in urine exosomes may serve as a potential biomarker for lung cancer diagnosis. BMC Cancer, 2023, 23(1): 1125.
57.	Niu L, Song X, Wang N, et al. Tumor-derived exosomal proteins as diagnostic biomarkers in non-small cell lung cancer. Cancer Sci, 2019, 110(1): 433-442.
58.	She W, Garitaonaindia Y, Lin Y. The latest advances in liquid biopsy for lung cancer: a narrative review. Transl Lung Cancer Res, 2024, 13(11): 3241-3251.
59.	Liu Q, Zhang J, Guo C, et al. Proteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies. Cell, 2024, 187(1): 184-203. e28.
60.	Krizova L, Benesova I, Zemanova P, et al. Immunophenotyping of peripheral blood in NSCLC patients discriminates responders to immune checkpoint inhibitors. J Cancer Res Clin Oncol, 2024, 150(2): 99.
61.	Li H, Du S, Dai J, et al. Proteome-wide Mendelian randomization identifies causal plasma proteins in lung cancer. iScience, 2024, 27(2): 108985.
62.	Su S, Chen F, Lv X, et al. Predictive value of peripheral blood biomarkers in patients with non-small-cell lung cancer responding to anti-PD-1-based treatment. Cancer Immunol Immunother, 2024, 73(1): 12.
63.	Ciofiac CM, M?muleanu M, Florescu LM, et al. CT imaging patterns in major histological types of lung cancer. Life (Basel), 2024, 14(4): 462.
64.	Li P, Liu S, Du L, et al. Liquid biopsies based on DNA methylation as biomarkers for the detection and prognosis of lung cancer. Clin Epigenetics, 2022, 14(1): 118.
65.	Zhang W, Campbell DH, Walsh BJ, et al. Cancer-derived small extracellular vesicles: emerging biomarkers and therapies for pancreatic ductal adenocarcinoma diagnosis/prognosis and treatment. J Nanobiotechnology, 2022, 20(1): 446.
66.	Martínez-Espinosa I, Serrato JA, Cabello-Gutiérrez C, et al. Exosome-derived miRNAs in liquid biopsy for lung cancer. Life (Basel), 2024, 14(12): 1608.
67.	Sun Y, Fang L, Yi Y, et al. Multistage nucleic acid amplification induced nano-aggregation for 3D hotspots-improved SERS detection of circulating miRNAs. J Nanobiotechnology, 2022, 20(1): 285.
68.	Zuo YB, Zhang YF, Zhang R, et al. Ferroptosis in cancer progression: role of noncoding RNAs. Int J Biol Sci, 2022, 18(5): 1829-1843.
69.	Liu Q, Li S. Exosomal circRNAs: novel biomarkers and therapeutic targets for urinary tumors. Cancer Lett, 2024, 588: 216759.
70.	Yin H, Shi J, Li S, et al. Emerging roles of exosomal circRNAs in non-small cell lung cancer. J Transl Med, 2025, 23(1): 490.

1. Leiter A, Veluswamy RR, Wisnivesky JP. The global burden of lung cancer: current status and future trends. Nat Rev Clin Oncol, 2023, 20(9): 624-639.
2. Feng R, Su Q, Huang X, et al. Cancer situation in China: what does the China cancer map indicate from the first national death survey to the latest cancer registration? Cancer Commun (Lond), 2023, 43(1): 75-86.
3. Giaccone G, He Y. Current knowledge of small cell lung cancer transformation from non-small cell lung cancer. Semin Cancer Biol, 2023, 94: 1-10.
4. Galetta D. Advances in lung cancer therapy. Cancers (Basel), 2023, 15(10): 2671.
5. Shimizu K, Ohtaki Y, Suzuki K, et al. Salvage surgery for non-small cell lung cancer after definitive radiotherapy. Ann Thorac Surg, 2021, 112(3): 862-873.
6. Wang Y, Li C, Wang Z, et al. Comparison between immunotherapy efficacy in early non-small cell lung cancer and advanced non-small cell lung cancer: a systematic review. BMC Med, 2022, 20(1): 426.
7. Bodor JN, Boumber Y, Borghaei H. Biomarkers for immune checkpoint inhibition in non-small cell lung cancer (NSCLC). Cancer, 2020, 126(2): 260-270.
8. Zhou B, Xu K, Zheng X, et al. Application of exosomes as liquid biopsy in clinical diagnosis. Signal Transduct Target Ther, 2020, 5(1): 144.
9. Shen H, Jin Y, Zhao H, et al. Potential clinical utility of liquid biopsy in early-stage non-small cell lung cancer. BMC Med, 2022, 20(1): 480.
10. Li W, Liu JB, Hou LK, et al. Liquid biopsy in lung cancer: significance in diagnostics, prediction, and treatment monitoring. Mol Cancer, 2022, 21(1): 25.
11. Ren F, Fei Q, Qiu K, et al. Liquid biopsy techniques and lung cancer: diagnosis, monitoring and evaluation. J Exp Clin Cancer Res, 2024, 43(1): 96.
12. Siravegna G, Mussolin B, Venesio T, et al. How liquid biopsies can change clinical practice in oncology. Ann Oncol, 2019, 30(10): 1580-1590.
13. Ignatiadis M, Sledge GW, Jeffrey SS. Liquid biopsy enters the clinic-implementation issues and future challenges. Nat Rev Clin Oncol, 2021, 18(5): 297-312.
14. Connal S, Cameron JM, Sala A, et al. Liquid biopsies: the future of cancer early detection. J Transl Med, 2023, 21(1): 118.
15. Tarasov VV, Svistunov AA, Chubarev VN, et al. Extracellular vesicles in cancer nanomedicine. Semin Cancer Biol, 2021, 69: 212-225.
16. Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science, 2020, 367(6478): eaau6977.
17. Sadik N, Cruz L, Gurtner A, et al. Extracellular RNAs: a new awareness of old perspectives. Methods Mol Biol, 2018, 1740: 1-15.
18. Zhao L, Wang H, Fu J, et al. Microfluidic-based exosome isolation and highly sensitive aptamer exosome membrane protein detection for lung cancer diagnosis. Biosens Bioelectron, 2022, 214: 114487.
19. Zhang X, Xu Y, Ma L, et al. Essential roles of exosome and circRNA_101093 on ferroptosis desensitization in lung adenocarcinoma. Cancer Commun (Lond), 2022, 42(4): 287-313.
20. Shang R, Lee S, Senavirathne G, et al. microRNAs in action: biogenesis, function and regulation. Nat Rev Genet, 2023, 24(12): 816-833.
21. Li C, Zhou T, Chen J, et al. The role of exosomal miRNAs in cancer. J Transl Med, 2022, 20(1): 6.
22. Kim DH, Park H, Choi YJ, et al. Identification of exosomal microRNA panel as diagnostic and prognostic biomarker for small cell lung cancer. Biomark Res, 2023, 11(1): 80.
23. Zhang Q, Zheng K, Gao Y, et al. Plasma exosomal miR-1290 and miR-29c-3p as diagnostic biomarkers for lung cancer. Heliyon, 2023, 9(10): e21059.
24. Zheng B, Peng M, Gong J, et al. Circulating exosomal microRNA-4497 as a potential biomarker for metastasis and prognosis in non-small-cell lung cancer. Exp Biol Med (Maywood), 2023, 248(16): 1403-1413.
25. Zhang Z, Tang Y, Song X, et al. Tumor-derived exosomal miRNAs as diagnostic biomarkers in non-small cell lung cancer. Front Oncol, 2020, 10: 560025.
26. Hassanin AAI, Ramos KS. Circulating exosomal miRNA profiles in non-small cell lung cancers. Cells, 2024, 13(18): 1562.
27. Lu S, Kato T, Dong X, et al. Osimertinib after chemoradiotherapy in stage Ⅲ EGFR-mutated NSCLC. N Engl J Med, 2024, 391(7): 585-597.
28. Padinharayil H, Varghese J, John MC, et al. Non-small cell lung carcinoma (NSCLC): implications on molecular pathology and advances in early diagnostics and therapeutics. Genes Dis, 2023, 10(3): 960-989.
29. 李紀遠, 馬新, 張燦斌, 等. 血清外泌體miR-20b-5p miR-107水平檢測在非小細胞肺腺癌診斷及預后評估中的應用. 安徽醫學, 2023, 44(1): 38-44.Li JY, Ma X, Zhang CB, et al. Application of serum exosomal miR-20b-5p and miR-107 in diagnosis and prognosis evaluation of non-small cell lung adenocarcinoma. Anhui Med J, 2023, 44(1): 38-44.
30. Mu X, Yu C, Zhao Y, et al. Exosomal miR-1228-5p down-regulates DUSP22 to promotes cell proliferation and migration in small cell lung cancer. Life Sci, 2024, 351: 122787.
31. Wang Z, Yang B, Zhang M, et al. LncRNA epigenetic landscape analysis identifies EPIC1 as an oncogenic lncRNA that interacts with MYC and promotes cell-cycle progression in cancer. Cancer Cell, 2018, 33(4): 706-720. e9.
32. Li C, Lv Y, Shao C, et al. Tumor-derived exosomal lncRNA GAS5 as a biomarker for early-stage non-small-cell lung cancer diagnosis. J Cell Physiol, 2019, 234(11): 20721-20727.
33. Xiong D, Wang C, Yang Z, et al. Clinical significance of serum-derived exosomal LINC00917 in patients with non-small cell lung cancer. Front Genet, 2021, 12: 728763.
34. Tao Y, Tang Y, Yang Z, et al. Exploration of serum exosomal LncRNA TBILA and AGAP2-AS1 as promising biomarkers for diagnosis of non-small cell lung cancer. Int J Biol Sci, 2020, 16(3): 471-482.
35. Zhang C, Xu L, Deng G, et al. Exosomal HOTAIR promotes proliferation, migration and invasion of lung cancer by sponging miR-203. Sci China Life Sci, 2020, 63(8): 1265-1268.
36. Chen L, Huang S, Huang J, et al. Role and mechanism of exosome-derived long noncoding RNA HOTAIR in lung cancer. ACS Omega, 2021, 6(27): 17217-17227.
37. Xian J, Zeng Y, Chen S, et al. Discovery of a novel linc01125 isoform in serum exosomes as a promising biomarker for NSCLC diagnosis and survival assessment. Carcinogenesis, 2021, 42(6): 831-841.
38. Min L, Zhu T, Lv B, et al. Exosomal lncRNA RP5-977B1 as a novel minimally invasive biomarker for diagnosis and prognosis in non-small cell lung cancer. Int J Clin Oncol, 2022, 27(6): 1013-1024.
39. Ma X, Chen Z, Chen W, et al. LncRNA AL139294.1 can be transported by extracellular vesicles to promote the oncogenic behaviour of recipient cells through activation of the Wnt and NF-κB2 pathways in non-small-cell lung cancer. J Exp Clin Cancer Res, 2024, 43(1): 20.
40. Wang L, Xie Y, Wang J, et al. Characterization of a novel LUCAT1/miR-4316/VEGF-A axis in metastasis and glycolysis of lung adenocarcinoma. Front Cell Dev Biol, 2022, 10: 833579.
41. Song X, Duan L, Dong Y. Diagnostic accuracy of exosomal long noncoding RNAs in diagnosis of NSCLC: a meta-analysis. Mol Diagn Ther, 2024, 28(4): 455-468.
42. Wang MC, Gong GY, Wang CL, et al. Methods for collection of extracellular vesicles and their content RNA as liquid biopsy for lung cancer detection: application of differential centrifugation and annexin A5 coated beads. Curr Issues Mol Biol, 2022, 44(5): 2374-2386.
43. Kang Y, You J, Gan Y, et al. Serum and serum exosomal circRNAs hsa_circ_0001492, hsa_circ_0001439, and hsa_circ_0000896 as diagnostic biomarkers for lung adenocarcinoma. Front Oncol, 2022, 12: 912246.
44. Zhou H, Huang X, Yang X, et al. CircRAPGEF5 promotes the proliferation and metastasis of lung adenocarcinoma through the miR-1236-3p/ZEB1 axis and serves as a potential biomarker. Int J Biol Sci, 2022, 18(5): 2116-2131.
45. He Y, Liu Y, Cha N, et al. Exosomal circ_0048856 derived from non-small cell lung cancer contributes to aggressive cancer progression through downregulation of miR-1287-5p. Pathol Res Pract, 2022, 232: 153659.
46. Huang Y, Qin S, Gu X, et al. Comprehensive assessment of serum hsa_circ_0070354 as a novel diagnostic and predictive biomarker in non-small cell lung cancer. Front Genet, 2021, 12: 796776.
47. Xian J, Su W, Liu L, et al. Identification of three circular RNA cargoes in serum exosomes as diagnostic biomarkers of non-small-cell lung cancer in the Chinese population. J Mol Diagn, 2020, 22(8): 1096-1108.
48. Chen Y, Lou C, Ma X, et al. Serum exosomal hsa_circ_0069313 has a potential to diagnose more aggressive non-small cell lung cancer. Clin Biochem, 2022, 102: 56-64.
49. Zhou T, Ma H, Li Z, et al. Exosomes in lung cancer: a role in early diagnosis. Front Oncol, 2025, 15: 1599608.
50. Yoneyama T, Gorry M, Sobo-Vujanovic A, et al. ADAM10 sheddase activity is a potential lung-cancer biomarker. J Cancer, 2018, 9(14): 2559-2570.
51. Ma Y, Marinkova R, Nenkov M, et al. Tumor-intrinsic PD-L1 exerts an oncogenic function through the activation of the Wnt/β-catenin pathway in human non-small cell lung cancer. Int J Mol Sci, 2022, 23(19): 11031.
52. Li C, Li C, Zhi C, et al. Clinical significance of PD-L1 expression in serum-derived exosomes in NSCLC patients. J Transl Med, 2019, 17(1): 355.
53. Zhang Z, Jin W, Xu K, et al. Blood exosome PD-L1 is associated with PD-L1 expression measured by immunohistochemistry, and lymph node metastasis in lung cancer. Tissue Cell, 2022, 79: 101941.
54. Choi ES, Faruque HA, Kim JH, et al. CD5L as an extracellular vesicle-derived biomarker for liquid biopsy of lung cancer. Diagnostics (Basel), 2021, 11(4): 620.
55. Jeong H, Choi BH, Park J, et al. GCC2 as a new early diagnostic biomarker for non-small cell lung cancer. Cancers (Basel), 2021, 13(21): 5482.
56. Jin S, Liu T, Wang W, et al. Lymphocyte migration regulation related proteins in urine exosomes may serve as a potential biomarker for lung cancer diagnosis. BMC Cancer, 2023, 23(1): 1125.
57. Niu L, Song X, Wang N, et al. Tumor-derived exosomal proteins as diagnostic biomarkers in non-small cell lung cancer. Cancer Sci, 2019, 110(1): 433-442.
58. She W, Garitaonaindia Y, Lin Y. The latest advances in liquid biopsy for lung cancer: a narrative review. Transl Lung Cancer Res, 2024, 13(11): 3241-3251.
59. Liu Q, Zhang J, Guo C, et al. Proteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies. Cell, 2024, 187(1): 184-203. e28.
60. Krizova L, Benesova I, Zemanova P, et al. Immunophenotyping of peripheral blood in NSCLC patients discriminates responders to immune checkpoint inhibitors. J Cancer Res Clin Oncol, 2024, 150(2): 99.
61. Li H, Du S, Dai J, et al. Proteome-wide Mendelian randomization identifies causal plasma proteins in lung cancer. iScience, 2024, 27(2): 108985.
62. Su S, Chen F, Lv X, et al. Predictive value of peripheral blood biomarkers in patients with non-small-cell lung cancer responding to anti-PD-1-based treatment. Cancer Immunol Immunother, 2024, 73(1): 12.
63. Ciofiac CM, M?muleanu M, Florescu LM, et al. CT imaging patterns in major histological types of lung cancer. Life (Basel), 2024, 14(4): 462.
64. Li P, Liu S, Du L, et al. Liquid biopsies based on DNA methylation as biomarkers for the detection and prognosis of lung cancer. Clin Epigenetics, 2022, 14(1): 118.
65. Zhang W, Campbell DH, Walsh BJ, et al. Cancer-derived small extracellular vesicles: emerging biomarkers and therapies for pancreatic ductal adenocarcinoma diagnosis/prognosis and treatment. J Nanobiotechnology, 2022, 20(1): 446.
66. Martínez-Espinosa I, Serrato JA, Cabello-Gutiérrez C, et al. Exosome-derived miRNAs in liquid biopsy for lung cancer. Life (Basel), 2024, 14(12): 1608.
67. Sun Y, Fang L, Yi Y, et al. Multistage nucleic acid amplification induced nano-aggregation for 3D hotspots-improved SERS detection of circulating miRNAs. J Nanobiotechnology, 2022, 20(1): 285.
68. Zuo YB, Zhang YF, Zhang R, et al. Ferroptosis in cancer progression: role of noncoding RNAs. Int J Biol Sci, 2022, 18(5): 1829-1843.
69. Liu Q, Li S. Exosomal circRNAs: novel biomarkers and therapeutic targets for urinary tumors. Cancer Lett, 2024, 588: 216759.
70. Yin H, Shi J, Li S, et al. Emerging roles of exosomal circRNAs in non-small cell lung cancer. J Transl Med, 2025, 23(1): 490.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Latest ArticlesProgress in the application of exosomes in liquid biopsy for early diagnosis and screening of lung cancer

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