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Plasma-Derived Exosomal tRF-Phe-GAA-001 and tRF-Gly-GCC-037 as Novel Diagnostic Biomarkers for Cervical Cancer

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Abstract

This study delves into the exploration of exosomal transfer RNA-derived fragments (tRFs) as potential diagnostic markers for cervical cancer (CC). Employing plasma-derived exosomes isolated through ultracentrifugation and confirmed via transmission electron microscopy (TEM), qNano, and western blot analysis, we extracted total RNA from CC and adjacent tissues (n = 48), alongside exosomes from cervical cancer patients (n = 140) and healthy donors (n = 140) using Trizol reagents. The expression of exosomal tRFs was assessed through quantitative polymerase chain reaction (qPCR) and subjected to statistical analysis using Mann–Whitney U or t-tests, along with receiver operating characteristic (ROC) analysis. The findings unveiled a significant downregulation of exosomal tRF-Phe-GAA-001 and tRF-Gly-GCC-037 in both CC tissues and plasma samples from early-stage patients compared to healthy controls. Remarkably, these two exosomal tRFs exhibited promising capabilities as circulating biomarkers for both the diagnosis and early detection of CC, as evidenced by their high area under the curve (AUC) values of 0.9337 and 0.9432, respectively. Consequently, exosomal tRF-Phe-GAA-001 and tRF-Gly-GCC-037 were downregulated in CC and early-stage CC, indicating their potential as innovative non-invasive biomarkers for early CC diagnosis.

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References

  1. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, 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):229–63.

    Article  PubMed  Google Scholar 

  2. Vaccarella S, Lortet-Tieulent J, Plummer M, Franceschi S, Bray F. Worldwide trends in cervical cancer incidence: impact of screening against changes in disease risk factors. Eur J Cancer. 2013;49(15):3262–73.

    Article  PubMed  Google Scholar 

  3. Godinez J, Gombos EC, Chikarmane SA, Griffin GK, Birdwell RL. Breast MRI in the evaluation of eligibility for accelerated partial breast irradiation. AJR Am J Roentgenol. 2008;191(1):272–7.

    Article  PubMed  Google Scholar 

  4. Sun C, Fu Z, Wang S, Li J, Li Y, Zhang Y, et al. Roles of tRNA-derived fragments in human cancers. Cancer Lett. 2018;414:16–25.

    Article  CAS  PubMed  Google Scholar 

  5. Xie Y, Yao L, Yu X, Ruan Y, Li Z, Guo J. Action mechanisms and research methods of tRNA-derived small RNAs. Signal Transduct Target Ther. 2020;5(1):109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kumar P, Kuscu C, Dutta A. Biogenesis and function of transfer RNA-related fragments (tRFs). Trends Biochem Sci. 2016;41(8):679–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ivanov P, Emara MM, Villen J, Gygi SP, Anderson P. Angiogenin-induced tRNA fragments inhibit translation initiation. Mol Cell. 2011;43(4):613–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Maute RL, Schneider C, Sumazin P, Holmes A, Califano A, Basso K, et al. tRNA-derived microRNA modulates proliferation and the DNA damage response and is down-regulated in B cell lymphoma. Proc Natl Acad Sci USA. 2013;110(4):1404–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Goodarzi H, Liu X, Nguyen HC, Zhang S, Fish L, Tavazoie SF. Endogenous tRNA-derived fragments suppress breast cancer progression via YBX1 displacement. Cell. 2015;161(4):790–802.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lasser C, Alikhani VS, Ekstrom K, Eldh M, Paredes PT, Bossios A, et al. Human saliva, plasma and breast milk exosomes contain RNA: uptake by macrophages. J Transl Med. 2011;9:9.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Mathieu M, Martin-Jaular L, Lavieu G, Thery C. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol. 2019;21(1):9–17.

    Article  CAS  PubMed  Google Scholar 

  12. Bastos N, Ruivo CF, da Silva S, Melo SA. Exosomes in cancer: Use them or target them? Semin Cell Dev Biol. 2018;78:13–21.

    Article  CAS  PubMed  Google Scholar 

  13. Kahroba H, Hejazi MS, Samadi N. Exosomes: from carcinogenesis and metastasis to diagnosis and treatment of gastric cancer. Cell Mol Life Sci. 2019;76(9):1747–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Wang J, Ma G, Li M, Han X, Xu J, Liang M, et al. Plasma tRNA fragments derived from 5’ ends as novel diagnostic biomarkers for early-stage breast cancer. Mol Ther Nucleic Acids. 2020;21:954–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Lin C, Zheng L, Huang R, Yang G, Chen J, Li H. tRFs as potential exosome tRNA-derived fragment biomarkers for gastric carcinoma. Clin Lab. 2020. https://doi.org/10.7754/Clin.Lab.2019.190811.

    Article  PubMed  Google Scholar 

  16. Stromme O, Heck KA, Brede G, Lindholm HT, Otterlei M, Arum CJ. tRNA-derived fragments as biomarkers in bladder cancer. Cancers (Basel). 2024;16(8):1588.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Zheng B, Song X, Wang L, Zhang Y, Tang Y, Wang S, et al. Plasma exosomal tRNA-derived fragments as diagnostic biomarkers in non-small cell lung cancer. Front Oncol. 2022;12:1037523.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zhang Q, Liu Z, Han X, Li Y, Xia T, Zhu Y, et al. Circulatory exosomal tRF-Glu-CTC-005 and tRF-Gly-GCC-002 serve as predictive factors of successful microdissection testicular sperm extraction in patients with nonobstructive azoospermia. Fertil Steril. 2022;117(3):512–21.

    Article  PubMed  Google Scholar 

  19. Ko HH, Lee JJ, Chen HM, Kok SH, Yen-Ping Kuo M, Cheng SJ, et al. Upregulation of vascular endothelial growth factor mRNA level is significantly related to progression and prognosis of oral squamous cell carcinomas. J Formos Med Assoc. 2015;114(7):605–11.

    Article  CAS  PubMed  Google Scholar 

  20. Cheng L, Kong B, Zhao Y, Jiang J. miR-494 inhibits cervical cancer cell proliferation through upregulation of SOCS6 expression. Oncol Lett. 2018;15(3):3075–80.

    PubMed  Google Scholar 

  21. Kong Q, Tang Z, Xiang F, Jiang J, Yue H, Wu R, et al. Diagnostic value of serum hsa-mir-92a in patients with cervical cancer. Clin Lab. 2017;63(2):335–40.

    CAS  PubMed  Google Scholar 

  22. Li N, Wang Y, Che S, Yang Y, Piao J, Liu S, et al. HBXIP over expression as an independent biomarker for cervical cancer. Exp Mol Pathol. 2017;102(1):133–7.

    Article  CAS  PubMed  Google Scholar 

  23. Kim HJ, Kim CY, Jin J, Bae MK, Kim YH, Ju W, et al. Aberrant single-minded homolog 1 methylation as a potential biomarker for cervical cancer. Diagn Cytopathol. 2018;46(1):15–21.

    Article  PubMed  Google Scholar 

  24. Olvedy M, Scaravilli M, Hoogstrate Y, Visakorpi T, Jenster G, Martens-Uzunova ES. A comprehensive repertoire of tRNA-derived fragments in prostate cancer. Oncotarget. 2016;7(17):24766–77.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Wang X, Yang Y, Tan X, Mao X, Wei D, Yao Y, et al. Identification of tRNA-derived fragments expression profile in breast cancer tissues. Curr Genomics. 2019;20(3):199–213.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Telonis AG, Rigoutsos I. Race disparities in the contribution of miRNA isoforms and tRNA-derived fragments to triple-negative breast cancer. Cancer Res. 2018;78(5):1140–54.

    Article  CAS  PubMed  Google Scholar 

  27. Chuffa LG, Lupi-Junior LA, Costa AB, Amorim JP, Seiva FR. The role of sex hormones and steroid receptors on female reproductive cancers. Steroids. 2017;118:93–108.

    Article  CAS  PubMed  Google Scholar 

  28. Zhang M, Li F, Wang J, He W, Li Y, Li H, et al. tRNA-derived fragment tRF-03357 promotes cell proliferation, migration and invasion in high-grade serous ovarian cancer. Onco Targets Ther. 2019;12:6371–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Shao Y, Sun Q, Liu X, Wang P, Wu R, Ma Z. tRF-Leu-CAG promotes cell proliferation and cell cycle in non-small cell lung cancer. Chem Biol Drug Des. 2017;90(5):730–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Huang B, Yang H, Cheng X, Wang D, Fu S, Shen W, et al. tRF/miR-1280 suppresses stem cell-like cells and metastasis in colorectal cancer. Cancer Res. 2017;77(12):3194–206.

    Article  CAS  PubMed  Google Scholar 

  31. Li S, Shi X, Chen M, Xu N, Sun D, Bai R, et al. Angiogenin promotes colorectal cancer metastasis via tiRNA production. Int J Cancer. 2019;145(5):1395–407.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by Tianjin Binhai New Area Health Commission Science and Technology Project (2022BWKO024).

Funding

Tianjin Binhai New Area Health Commission Science and Technology Project (2022BWKQ024).

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Authors and Affiliations

  1. Department of Clinical Laboratory, Tianjin Medical University Cancer Institute and Hospital: Tianjin Tumor Hospital, Tianjin, China

    Zheng Li & Peng Ge

  2. Department of Clinical Laboratory, Tianjin Cancer Hospital Airport Hospital, National Clinical Research Center for Cancer, No. 99 East Fifth Road, Airport Economic Zone, Tianjin, China

    Zheng Li, Hongyan Wang, Ruijun Yang, Xiangchun Jin, Qing Han, Zhaoyuan She & Peng Ge

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  1. Zheng Li
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Contributions

All authors participated in the design, interpretation of the studies and analysis of the data and review of the manuscript; ZL and PG designed the experiments; ZL, HYW, RJY, and XCJ performed the experiments; QH did the statistical analysis; ZL and ZYS wrote the paper. The final manuscript has the approval of all authors.

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Correspondence to Peng Ge.

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Li, Z., Wang, H., Yang, R. et al. Plasma-Derived Exosomal tRF-Phe-GAA-001 and tRF-Gly-GCC-037 as Novel Diagnostic Biomarkers for Cervical Cancer. Ind J Clin Biochem (2024). https://doi.org/10.1007/s12291-024-01235-7

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  • DOI: https://doi.org/10.1007/s12291-024-01235-7

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