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LncRNA H19 is a potential biomarker and correlated with immune infiltration in thyroid carcinoma

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Abstract

The bulk of evidence has revealed that dysregulated expression of long non-coding RNAs (lncRNAs) plays a crucial functional role in cancer biology. However, the mechanistic role of lncRNAs in the initiation, progression and immune landscape of thyroid carcinoma (THCA) still remains largely unknown. This study aimed to explore the significance of H19 in the diagnostic and immune related roles in THCA. The expression level of H19 was analyzed using the TNMplot, GSCA, UALCAN, GEPIA, Wanderer, UCSC Xena and GEO databases. Enrichment analyses were performed to investigate the possible underlying biological pathways by LinkedOmics. Moreover, cBioPortal web tool was used to analyze genetic alterations of H19. Finally, we used TIMER and GEPIA databases to explore the correlations between H19 and tumor-infiltrated immune cells and immune markers. LncRNA H19 was differentially expressed in various cancers and also remarkably downregulated in the THCA tissues compared to the normal ones. Genetic alteration analysis revealed that there was a significant correlation between alterations in H19 and overall survival of THCA patients. Furthermore, enrichment analysis indicated the functional relationship between co-expression network of H19 and extracellular structure organization, and immune microenvironment. In addition, H19 expression was positively correlated with infiltration level of diverse immune cells including CD4+T cells, CD8+T cells, B cells, dendritic cells, neutrophils and macrophages and was closely associated with multiple immune markers in THCA. Conclusively, this comprehensive study indicates the lncRNA H19 might have a significant role in the initiation and progression of THCA. Hence, our findings might provide ideas on the selection of novel diagnostic biomarkers and assist in the designing of the effective pharmaceutical targets for THCA.

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References

  1. Bartha Á, Győrffy B. TNMplot. com: a web tool for the comparison of gene expression in normal, tumor and metastatic tissues. Int J Mol Sci. 2021;22(5):2622.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bhaijee F, Nikiforov YE. Molecular analysis of thyroid tumors. Endocr Pathol. 2011;22:126–33.

    Article  CAS  PubMed  Google Scholar 

  3. Chandrashekar DS, Bashel B, Balasubramanya SAH, et al. UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia. 2017;19:649–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Durante C, Haddy N, Baudin E, et al. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J Clin Endocrinol Metab. 2006;91:2892–9.

    Article  CAS  PubMed  Google Scholar 

  5. Fagin JA, Wells SA Jr. Biologic and clinical perspectives on thyroid cancer. N Engl J Med. 2016;375:1054–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Fridman WH, Galon J, Dieu-Nosjean MC, et al. Immune infiltration in human cancer: prognostic significance and disease control. Cancer Immunol Immunother. 2010; p. 1–24

  7. Gabory A, Ripoche M-A, Yoshimizu T, Dandolo L. The H19 gene: regulation and function of a non-coding RNA. Cytogenet Genome Res. 2006;113:188–93.

    Article  CAS  PubMed  Google Scholar 

  8. Gamaev L, Mizrahi L, Friehmann T, et al. The pro-oncogenic effect of the lncRNA H19 in the development of chronic inflammation-mediated hepatocellular carcinoma. Oncogene. 2021;40:127–39.

    Article  CAS  PubMed  Google Scholar 

  9. Gao J, Aksoy BA, Dogrusoz U, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013;6(269):pl1–pl1.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Goldman MJ, Craft B, Hastie M, et al. Visualizing and interpreting cancer genomics data via the Xena platform. Nat Biotechnol. 2020;38:675–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.

    Article  CAS  PubMed  Google Scholar 

  12. Jarroux J, Morillon A, Pinskaya M. History, discovery, and classification of lncRNAs. Long Non Coding RNA Biology. 2017; 1–46.

  13. Jiao X, Lu J, Huang Y, et al. Long non-coding RNA H19 may be a marker for prediction of prognosis in the follow-up of patients with papillary thyroid cancer. Cancer Biomark. 2019;26:203–7.

    Article  CAS  PubMed  Google Scholar 

  14. Khorkova O, Hsiao J, Wahlestedt C. Basic biology and therapeutic implications of lncRNA. Adv Drug Deliv Rev. 2015;87:15–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Lan X, Sun W, Dong W, et al. Downregulation of long noncoding RNA H19 contributes to the proliferation and migration of papillary thyroid carcinoma. Gene. 2018;646:98–105.

    Article  CAS  PubMed  Google Scholar 

  16. Lan X, Zhang H, Wang Z, et al. Genome-wide analysis of long noncoding RNA expression profile in papillary thyroid carcinoma. Gene. 2015;569:109–17.

    Article  CAS  PubMed  Google Scholar 

  17. Li M, Dal Maso L, Vaccarella S. Global trends in thyroid cancer incidence and the impact of overdiagnosis. Lancet Diabetes Endocrinol. 2020;8:468–70.

    Article  PubMed  Google Scholar 

  18. Li T, Fan J, Wang B, et al. TIMER: a web server for comprehensive analysis of tumor-infiltrating immune cells. Can Res. 2017;77:e108–10.

    Article  CAS  Google Scholar 

  19. Li X, Li Q, Jin X, et al. Long non-coding RNA H19 knockdown inhibits the cell viability and promotes apoptosis of thyroid cancer cells through regulating the PI3K/AKT pathway. Exp Ther Med. 2019;18:1863–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Li Y, Ma H-Y, Hu X-W, et al. LncRNA H19 promotes triple-negative breast cancer cells invasion and metastasis through the p53/TNFAIP8 pathway. Cancer Cell Int. 2020;20:1–14.

    PubMed  PubMed Central  Google Scholar 

  21. Liu C-J, Hu F-F, Xia M-X, et al. GSCALite: a web server for gene set cancer analysis. Bioinformatics. 2018;34:3771–2.

    Article  CAS  PubMed  Google Scholar 

  22. Liu L, Yang J, Zhu X, et al. Long noncoding RNA H19 competitively binds miR-17-5p to regulate YES 1 expression in thyroid cancer. FEBS J. 2016;283:2326–39.

    Article  CAS  PubMed  Google Scholar 

  23. Liu N, Zhou Q, Qi Y-H, et al. Effects of long non-coding RNA H19 and microRNA let7a expression on thyroid cancer prognosis. Exp Mol Pathol. 2017;103:71–7.

    Article  CAS  PubMed  Google Scholar 

  24. Pages F, Galon J, Dieu-Nosjean MC, et al. Immune infiltration in human tumors: a prognostic factor that should not be ignored. Oncogene. 2010;29:1093–102.

    Article  CAS  PubMed  Google Scholar 

  25. Park S-J, Yoon B-H, Kim S-K, Kim S-Y. GENT2: an updated gene expression database for normal and tumor tissues. BMC Med Genom. 2019;12:1–8.

    Article  CAS  Google Scholar 

  26. Roman BR, Morris LG, Davies L. The thyroid cancer epidemic, 2017 perspective. Curr Opin Endocrinol Diabetes Obes. 2017;24:332.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Sedaghati M, Kebebew E. Long noncoding RNAs in thyroid cancer. Curr Opin Endocrinol Diabetes Obes. 2019;26:275–81.

    Article  CAS  PubMed  Google Scholar 

  28. Tang Z, Li C, Kang B, et al. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45:W98–102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Tarabichi M, Saiselet M, Trésallet C, et al. Revisiting the transcriptional analysis of primary tumours and associated nodal metastases with enhanced biological and statistical controls: application to thyroid cancer. Br J Cancer. 2015;112:1665–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Tomás G, Tarabichi M, Gacquer D, et al. A general method to derive robust organ-specific gene expression-based differentiation indices: application to thyroid cancer diagnostic. Oncogene. 2012;31:4490–8.

    Article  PubMed  Google Scholar 

  31. Vasaikar SV, Straub P, Wang J, Zhang B. LinkedOmics: analyzing multi-omics data within and across 32 cancer types. Nucleic Acids Res. 2018;46:D956–63.

    Article  CAS  PubMed  Google Scholar 

  32. Wang J, Zhang X, Chen W, et al. Regulatory roles of long noncoding RNAs implicated in cancer hallmarks. Int J Cancer. 2020;146:906–16.

    Article  CAS  PubMed  Google Scholar 

  33. Whiteside TL. The tumor microenvironment and its role in promoting tumor growth. Oncogene. 2008;27:5904–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Xing M. BRAF mutation in thyroid cancer. Endocr Relat Cancer. 2005;12:245–62.

    Article  CAS  PubMed  Google Scholar 

  35. Xu G, Yuan Y, Wang M, et al. LncRNA H19 suppresses metastasis of follicular thyroid carcinoma via the IGF1/JAK/STAT pathway. STAT Pathway (11/29/2019). 2019.

  36. Zhang Y, Huang W, Yuan Y, et al. Long non-coding RNA H19 promotes colorectal cancer metastasis via binding to hnRNPA2B1. J Exp Clin Cancer Res. 2020;39:1–15.

    Article  Google Scholar 

  37. Zhang Y, Liu Q, Liao Q. Long noncoding RNA: a dazzling dancer in tumor immune microenvironment. J Exp Clin Cancer Res. 2020;39:1–25.

    Article  Google Scholar 

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  1. Department of Medical Biology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey

    Yunus Sahin

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  1. Yunus Sahin
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Sahin, Y. LncRNA H19 is a potential biomarker and correlated with immune infiltration in thyroid carcinoma. Clin Exp Med 23, 841–851 (2023). https://doi.org/10.1007/s10238-022-00853-w

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  • DOI: https://doi.org/10.1007/s10238-022-00853-w

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