AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025220223
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ORIGINAL RESEARCH ARTICLE

Transcriptome sequencing analysis of plasma-derived exosomal lncRNA, mRNA, and circRNA expression profiles in non-small cell lung cancer

Dan Zhao1† ,  Huimin Huang1,2† ,  Zhongzhi Liu1† ,  Kang Ling1 ,  Hao Wang3 ,  Jingjian Liu1 ,  Fengying Ran1,2* ,  Weidong Peng1*
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1 Department of Second Clinical College, Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Shiyan, Hubei, China
2 Department of Pharmacy, School of Pharmacy, Health Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi, China
3 Department of Medical Laboratory, Shiyan Hospital of Integrated Traditional and Western Medicine, Shiyan, Hubei, China
†These authors contributed equally to this work.
EJMO, 025220223 https://doi.org/10.36922/EJMO025220223
Received: 28 May 2025 | Revised: 21 August 2025 | Accepted: 10 October 2025 | Published online: 14 November 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Non-small cell lung cancer (NSCLC) is one of the most prevalent malignant tumors worldwide. The investigation of exosome-derived biomarkers from lung cancer for their potential applications in early diagnosis and targeted therapy remains a pivotal focus in contemporary biomedical research.

Objective: This study aims to identify differentially expressed RNAs—including mRNAs, long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and other non-coding RNAs—in plasma-derived exosomes from NSCLC patients through sequencing, and to analyze these RNAs using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and disease annotation enrichment databases.

Methods: High-throughput sequencing technology was used to detect the expression of mRNAs, lncRNAs, and circRNAs in exosomes isolated from four NSCLC patients and four healthy controls. Differentially expressed RNAs were identified, and corresponding heatmaps and volcano plots were generated. GO, KEGG pathway, and disease enrichment analyses were performed. Furthermore, the expression levels of 12 upregulated RNAs were validated using quantitative real-time polymerase chain reaction.

Results: The analysis revealed 1,916 differentially expressed lncRNAs, 1,123 mRNAs, and 70 circRNAs. KEGG pathway enrichment analysis indicated that target genes of differentially expressed lncRNAs were primarily involved in endocytosis, tight junctions, and Salmonella infection pathways. Target genes of differentially expressed mRNAs were predominantly enriched in alanine, aspartate, and glutamate metabolism, neuroactive ligand–receptor interaction, and nicotine addiction-related pathways. Meanwhile, target genes of differentially expressed circRNAs were mainly associated with endocytosis, T-cell receptor signaling, and Th17 cell differentiation pathways.

Conclusion: This study provides a comprehensive overview of the expression changes of lncRNAs, mRNAs, and circRNAs in the plasma exosomes of NSCLC patients, highlighting their potential regulatory functions and associated signaling pathways. The findings offer valuable insights that may serve as a foundation for elucidating the molecular pathogenesis of NSCLC and for developing targeted therapeutic strategies.

Keywords
Non-small cell lung cancer
Exosome
Long non-coding RNA
mRNA
Circular RNA
Funding
This work was financially supported by the National Science Foundation of China (Grant No. 82272960), the Open Project of Hubei Clinical Research Center of Hypertension (Grant No. HBCH2024005), he Young Talent Project of Affiliated Dongfeng Hospital (Grant Nos. Y202522, Y202512 and Y202518), and the Science and Technology Key Program of Shiyan (Grant Nos: 24Y142, 24Y154 and 24Y161).
Conflict of interest
The authors affirm that no competing financial interests or personal relationships exist that could have influenced the conduct or reporting of this research.
References
  1. Thai AA, Solomon BJ, Sequist LV, Gainor JF, Heist RS. Lung cancer. Lancet. 2021;398(10299):535-554. doi: 10.1016/S0140-6736(21)00312-3

 

  1. Rong A, Han Z, Wang T, Zhu M, Zhou M, Sun X. Pulmonary delivery of nano-particles for lung cancer diagnosis and therapy: Recent advances and future prospects. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2024;16(1):e1933. doi: 10.1002/wnan.1933

 

  1. Guo X, Chen S, Wang X, Liu X. Immune-related pulmonary toxicities of checkpoint inhibitors in non-small cell lung cancer: Diagnosis, mechanism, and treatment strategies. Front Immunol. 2023;14:1138483. doi: 10.3389/fimmu.2023.1138483

 

  1. Thomas NA, New ML. Biomarkers in lung cancer diagnosis and bronchoscopy: Current landscape and future directions. Cancer Biomark. 2025;42(1):453479482. doi: 10.1177/18758592241306682

 

  1. Nooreldeen R, Bach H. Current and future development in lung cancer diagnosis. Int J Mol Sci. 2021;22(16):8661. doi: 10.3390/ijms22168661

 

  1. 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. doi: 10.1186/s12916-022-02681-x

 

  1. Somayaji D, Mohedat H, Dean GE, Dickerson SS. Patients’ perceptions at diagnosis: Lung cancer discovery and provider relationships. Cancer Nurs. 2022;45(5):397-405. doi: 10.1097/NCC.0000000000001050

 

  1. Chang J, Zhang L, Li Z, Qian C, Du J. Exosomal non-coding rnas (ncrnas) as potential biomarkers in tumor early diagnosis. Biochim Biophys Acta Rev Cancer. 2024;1879(6):189188. doi: 10.1016/j.bbcan.2024.189188

 

  1. Imran M, Altamimi ASA, Babu MA, et al. Non-coding rnas (ncrnas) as therapeutic targets and biomarkers in oligodendroglioma. Pathol Res Pract. 2024;264:155708. doi: 10.1016/j.prp.2024.155708

 

  1. Wen K, Chen X, Gu J, Chen Z, Wang Z. Beyond traditional translation: Ncrna derived peptides as modulators of tumor behaviors. J Biomed Sci. 2024;31(1):63. doi: 10.1186/s12929-024-01047-0

 

  1. Wang J, Zhu S, Meng N, He Y, Lu R, Yan G. Ncrna-encoded peptides or proteins and cancer. Mol Ther. 2019;27(10):1718-1725. doi: 10.1016/j.ymthe.2019.09.001

 

  1. Sanchez A, Lhuillier J, Grosjean G, Ayadi L, Maenner S. The long non-coding rna anril in cancers. Cancers (Basel). 2023;15(16):4160. doi: 10.3390/cancers15164160

 

  1. Ahsan S, Win TT, Aye SN, Than NN. The role of circular rnas (circrnas) as a prognostic factor in lung cancer: A meta-analysis. BMC Cancer. 2024;24(1):988. doi: 10.1186/s12885-024-12704-w

 

  1. Liu C, Chen L. Circular rnas: Characterization, cellular roles, and applications. Cell. 2022;185(12):2016-2034. doi: 10.1016/j.cell.2022.04.021

 

  1. Zhang C, Huang Y, Gao X, Ren H, Gao S, Zhu W. Biological functions of circrnas and their advance on skeletal muscle development in bovine. 3 Biotech. 2023;13(5):133. doi: 10.1007/s13205-023-03558-3

 

  1. Du X, Luo W, Li H, et al. Hsa_circ_0125356 promotes gemcitabine resistance by modulating wnt canonical and non-canonical pathways via mir-582-5p/fgf9 axis in non-small cell lung cancer. Mol Cancer. 2025;24(1):59. doi: 10.1186/s12943-025-02259-0

 

  1. Dance A. Circular logic: Understanding rna’s strangest form yet. Nature. 2024;635(8038):511-513. doi: 10.1038/d41586-024-03683-w

 

  1. Qian D, Qiu J, Xu Y, et al. Whole transcriptome sequencing indicated the anti-tumor immunity of nlrp3 in breast cancer. Genomics. 2024;116(5):110930. doi: 10.1016/j.ygeno.2024.110930

 

  1. Zhang J, Liu R, Xu A. Whole transcriptome sequencing analysis of blood plasma-derived exosomes from immune-related hearing loss. Int Immunopharmacol. 2023;120:110361. doi: 10.1016/j.intimp.2023.110361

 

  1. Hashimoto T, Nakamura Y, Mishima S, et al. Whole-transcriptome sequencing in advanced gastric or gastroesophageal cancer: A deep dive into its clinical potential. Cancer Sci. 2024;115(5):1622-1633. doi: 10.1111/cas.16109

 

  1. Zhou Y, Seo J, Tu S, Nanmo A, Kageyama T, Fukuda J. Exosomes for hair growth and regeneration. J Biosci Bioeng. 2024;137(1):1-8. doi: 10.1016/j.jbiosc.2023.11.001

 

  1. Lin H, Chen H, Zhao X, et al. Advances of exosomes in periodontitis treatment. J Transl Med. 2022;20(1):279. doi: 10.1186/s12967-022-03487-4

 

  1. Meldolesi J. Exosomes and ectosomes in intercellular communication. Curr Biol. 2018;28(8):R435-R444. doi: 10.1016/j.cub.2018.01.059

 

  1. Yu Z, Yang Y, Fang W, Hu P, Liu Y, Shi J. Dual tumor exosome biomarker co-recognitions based nanoliquid biopsy for the accurate early diagnosis of pancreatic cancer. ACS Nano. 2023;17(12):11384-11395. doi: 10.1021/acsnano.3c00674

 

  1. Soares Martins T, Marcalo R, Da Cruz E Silva CB, et al. Novel exosome biomarker candidates for Alzheimer’s disease unravelled through mass spectrometry analysis. Mol Neurobiol. 2022;59(5):2838-2854. doi: 10.1007/s12035-022-02762-1

 

  1. Goyal B, Yadav SRM, Awasthee N, Gupta S, Kunnumakkara AB, Gupta SC. Diagnostic, prognostic, and therapeutic significance of long non-coding rna malat1 in cancer. Biochim Biophys Acta Rev Cancer. 2021;1875(2):188502. doi: 10.1016/j.bbcan.2021.188502

 

  1. Wu D, Zhu J, Fu Y, Li C, Wu B. Lncrna hotair promotes breast cancer progression through regulating the mir-129-5p/fzd7 axis. Cancer Biomark. 2020;30(2):203-212. doi: 10.3233/CBM-190913

 

  1. Chen T, Liu Y, Li C, et al. Tumor-derived exosomal circfarsa mediates m2 macrophage polarization via the pten/pi3k/akt pathway to promote non-small cell lung cancer metastasis. Cancer Treat Res Commun. 2021;28:100412. doi: 10.1016/j.ctarc.2021.100412

 

  1. Rotem O, Zer A, Yosef L, et al. Blood-derived exosomal hTERT mRNA in patients with lung cancer: Characterization and correlation with response to therapy. Biomedicines. 2023;11(6):1730. doi: 10.3390/biomedicines11061730

 

  1. Hu Z, Wang N, Zhang Y, et al. Pd-l1 mrna derived from tumor-educated platelets as a potential immunotherapy biomarker in non-small cell lung cancer. Transl Lung Cancer Res. 2024;13(2):345-354. doi: 10.21037/tlcr-24-29

 

  1. Fu K, Wang X, Wang LJ. Role of peripheral blood t helper 17 cells in non-small cell lung cancer of different clinical stages, pathological types and differentiation degrees. Clin Lab. 2023;69(10):e220116. doi: 10.7754/Clin.Lab.2022.220116

 

  1. Kim B, Park YS, Sung JS, Lee JW, Lee SB, Kim YH. Clathrin-mediated egfr endocytosis as a potential therapeutic strategy for overcoming primary resistance of egfr tki in wild-type egfr non-small cell lung cancer. Cancer Med. 2021;10(1):372-385.doi: 10.1002/cam4.3635

 

  1. Sanchez-Cabrero D, Garcia-Guede A, Burdiel M, et al. Mir-124 as a liquid biopsy prognostic biomarker in small extracellular vesicles from nsclc patients. Int J Mol Sci. 2023;24(14):11464. doi: 10.3390/ijms241411464

 

  1. Talebi S, Abadi AJ, Kazemioula G, et al. Expression analysis of five different long non-coding ribonucleic acids in nonsmall-cell lung carcinoma tumor and tumor-derived exosomes. Diagnostics (Basel). 2022;12(12):3209. doi: 10.3390/diagnostics12123209

 

  1. Lin L, Yang L, Zeng Q, et al. Tumor-originated exosomal lncuegc1 as a circulating biomarker for early-stage gastric cancer. Mol Cancer. 2018;17(1):84. doi: 10.1186/s12943-018-0834-9

 

  1. Zhang R, Xia Y, Wang Z, et al. Serum long non coding rna malat-1 protected by exosomes is up-regulated and promotes cell proliferation and migration in non-small cell lung cancer. Biochem Biophys Res Commun. 2017;490(2):406-414. doi: 10.1016/j.bbrc.2017.06.055

 

  1. Miao D, Wang Y, Jia Y, Tong J, Jiang S, Liu L. Zranb1 enhances stem-cell-like features and accelerates tumor progression by regulating sox9-mediated usp22/wnt/beta-catenin pathway in colorectal cancer. Cell Signal. 2022;90:110200. doi: 10.1016/j.cellsig.2021.110200

 

  1. Wang S, Cheng Z, Cui Y, et al. Ptprh promotes the progression of non-small cell lung cancer via glycolysis mediated by the pi3k/akt/mtor signaling pathway. J Transl Med. 2023;21(1):819. doi: 10.1186/s12967-023-04703-5

 

  1. Li K, Niu Y, Li K, et al. Dysregulation of plod2 promotes tumor metastasis and invasion in hepatocellular carcinoma. J Clin Transl Hepatol. 2023;11(5):1094-1105. doi: 10.14218/JCTH.2022.00401

 

  1. Zhu G, OuYang S, Liu F, Zhu Z, Jiang F, Zhang B. Elevated expression of dlg1 is associated with poor prognosis in patients with colorectal cancer. Ann Clin Lab Sci. 2017;47(6):657-662.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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