Skip to main content

Advertisement

SpringerLink
Log in

Clinical Impact of Circulated miR-1291 in Plasma of Patients with Liver Cirrhosis (LC) and Hepatocellular Carcinoma (HCC): Implication on Glypican-3 Expression

  • Original Research
  • Published:
Journal of Gastrointestinal Cancer Aims and scope Submit manuscript

Abstract

Purpose

Liver cirrhosis (LC) is considered to be the end stage of chronic hepatopathies which may lead to hepatocellular carcinoma (HCC). Glypican-3 is one of the most promising serum markers for HCC. Abnormal expression of miRNAs may participate in cancer development and progression. In this study, we aimed to evaluate the relation between the expression of miR-1291 and GPC3 production as a non-invasive tool to differentiate patients with LC and HCC.

Methods

HCV patients (100) were divided into two groups; HCC (I) and LC (II). Fifty hepatitis-free subjects served as the control group (III). Expression of serum GPC3 was performed by enzyme-linked immunosorbent assay, and expression of circulating miR-1291 was performed by quantitative real-time polymerase chain reaction (qRT-PCR).

Results

Serum levels of GPC3 were significantly elevated in patients with HCC compared with the LC group. Both groups have increased GPC3 levels in relation to healthy controls. Serum GPC3 levels with a cutoff value of 619.5 pg/ml had a 50% sensitivity and 89.3% specificity while alpha-fetoprotein (AFP) with a cutoff value of 8.5 ng/ml had a higher sensitivity (87.5%) and specificity (100%) in the detection of HCC. The primary use of both markers improved the specificity to 100%. miR-1291 was significantly upregulated in HCC and LC patients compared with control subjects.

Conclusions

Our findings might indicate that miR-1291 exert oncogenic effects in hepatic carcinogenesis through positive regulation of GPC3 expression. We propose that GPC3 overexpression and its associated oncogenic effects are linked to the upregulation of miR-1291 in HCV patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Tsochatzis EA, Bosch J, Burroughs AK. Liver cirrhosis. Lancet. 2014;383(9930):1749–61.

    Article  Google Scholar 

  2. Harring TR, Guiteau JJ, Nguyen NT, et al. Building a comprehensive genomic program for hepatocellular carcinoma. World J Surg. 2011;35(8):1746–50.

    Article  Google Scholar 

  3. Omar A, Abou-Alfa GK, Khairy A, Omar H. Risk factors for developing hepatocellular carcinoma in Egypt. Chin Clin Oncol. 2013;2(4):43.

    PubMed  Google Scholar 

  4. Khairy A, Hamza I, Shaker O, Yosry A. Serum miRNA panel in Egyptian patients with chronic hepatitis C related hepatocellular carcinoma. APJCP. 2016;17(5):2699–703.

    PubMed  Google Scholar 

  5. Lu M, Kong X, Wang H, et al. A novel microRNAs expression signature for hepatocellular carcinoma diagnosis and prognosis. Oncotarget. 2017:8775–84.

  6. Masuzaki R, Karp SJ, Omata M. New serum markers of hepatocellular carcinoma. Semin Oncol. 2012;39:434–9.

    Article  CAS  Google Scholar 

  7. Attwa MH, El-Etreby SA. Guide for diagnosis and treatment of hepatocellular carcinoma. World J Hepatol. 2015;7:1632–51.

    Article  Google Scholar 

  8. Kudo M. Surveillance, diagnosis, treatment, and outcome of liver cancer in Japan. Liver Cancer. 2015;4:39–50.

    Article  Google Scholar 

  9. Schutte K, Schulz C, Malfertheiner P. Hepatocellular carcinoma: current concepts in diagnosis, staging, and treatment. Gastrointest Tumors. 2014;1(8):84–92.

    Article  Google Scholar 

  10. Filmus J, Selleck SB. Glypicans: proteoglycans with a surprise. J Clin Invest. 2001;108:497–501.

    Article  CAS  Google Scholar 

  11. Liu X, Wang S, Zhang K, et al. Expression of glypican three enriched hepatocellular carcinoma development-related genes and associated with carcinogenesis in cirrhotic livers. Carcinogenesis. 2015;36(2):232–42.

    Article  CAS  Google Scholar 

  12. Capurro M, Wanless IR, Sherman M, Deboer G, Shi W, Miyoshi E, et al. Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma. Gastroenterology. 2003;125:89–97.

    Article  CAS  Google Scholar 

  13. O’Donnell KA, Wentzel EA, Zeller KI, et al. c-Myc-regulated microRNAs modulate E2F1 expression. Nature. 2005;435:839–43.

    Article  Google Scholar 

  14. Giordano S, Columbano A. MicroRNAs: new tools for diagnosis, prognosis, and therapy in hepatocellular carcinoma? Hepatology. 2013;57:840–7.

    Article  CAS  Google Scholar 

  15. Zhang Y, Lib T, Qiu Y, et al. Serum microRNA panel for early diagnosis of the onset of hepatocellular carcinoma. Medicine. 2017:96–102.

  16. John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS. Human microRNA targets. PLoS Biol. 2004;2:e363.

    Article  Google Scholar 

  17. Childs-Disney JL, Disney MD. Small molecule targeting of microRNA associated with hepatocellular carcinoma. ACS Chem Biol. 2016;11(2):375–80 2016; 11(2); 375–80.

    Article  CAS  Google Scholar 

  18. Dickson JR, Kruse C, Montagna DR, Finsen B, Wolfe MS. Alternative polyadenylation and miR-34family members regulate tau expression. J Neurochem. 2013;127:739–49.

    Article  CAS  Google Scholar 

  19. Han M, Toli J, Abdellatif M. MicroRNAs in the cardiovascular system. Curr Opin Cardiol. 2011;26:181–9.

    Article  Google Scholar 

  20. Witwer KW. Circulating microRNA biomarker studies: pitfalls and potential solutions. Clin Chem. 2015;61:56–63.

    Article  CAS  Google Scholar 

  21. Tan Z, Zheng H, Liu X, Zhang W, Zhu J, Wu G, et al. MicroRNA-1229 overexpression promotes cell proliferation and tumorigenicity and activates Wnt/beta-catenin signaling in breast cancer. Oncotarget. 2016;7(17):24076–87.

    PubMed  PubMed Central  Google Scholar 

  22. Yan W, Qian L, Chen J, Chen W, Shen B. Comparison of prognostic microRNA biomarkers in blood and tissues for gastric cancer. J Cancer. 2016;7:95–106.

    Article  CAS  Google Scholar 

  23. Scott MS, Avolio F, Ono M, Lamond AI, Barton GJ. Human miRNA precursors with box H/ACA snoRNA features. PLoS Comput Biol. 2009;5:e1000507.

    Article  Google Scholar 

  24. Brameier M, Herwig A, Reinhardt R, Walter L, Gruber J. Human box C/D snoRNAs with miRNA like functions: expanding the range of regulatory RNAs. Nucleic Acids Res. 2011;39:675–86.

    Article  CAS  Google Scholar 

  25. Yu J, Ma Q, Zhang B, Ma RJ, Xu XG, Li MS, et al. Clinical application of specific antibody against glypican-3 for hepatocellular carcinoma diagnosis. Sci China Life Sci. 2013;56(3):234–9.

    Article  Google Scholar 

  26. Hidaka H, Seki N, Yoshino H, et al. Tumor suppressive microRNA-1285 regulates novel molecular targets: aberrant expression and functional significance in renal cell carcinoma. Oncotarget. 2012;3:44–57.

    Article  Google Scholar 

  27. Yamasaki T, Seki N, Yoshino H, Itesako T, Yamada Y, Tatarano S, et al. Tumor-suppressive microRNA-1291 directly regulates glucose transporter 1 in renal cell carcinoma. Cancer Sci. 2013;104:1411–9.

    Article  CAS  Google Scholar 

  28. Maurel M, Javy S, Ladeiro Y, et al. A functional screening identifies five microRNAs controlling glypican-3: role of miR-1271 down-regulation in hepatocellular carcinoma. Hepatology. 2013;57:195–204.

    Article  CAS  Google Scholar 

  29. Durand F, Valla D. Assessment of the prognosis of cirrhosis: Child-Pugh versus MELD. J Hepatol. 2005;42 Suppl(1):S100–7.

    Article  Google Scholar 

  30. Zhou L, Liu J, Luo F. Serum tumor markers for detection of hepatocellular carcinoma. World J Gastroenterol. 2006;12:1175–81.

    Article  CAS  Google Scholar 

  31. Hippo Y, Watanabe K, Watanabe A, Midorikawa Y, Yamamoto S, Ihara S, et al. Identification of soluble NH2-terminal fragment of glypican-3 as a serological marker for early-stage hepatocellular carcinoma. Cancer Res. 2004;64:2418–23.

    Article  CAS  Google Scholar 

  32. Lau WY, Lai EC. Hepatocellular carcinoma: current management and recent advances. Hepatobiliary Pancreat Dis Int. 2008;7:237–57.

    PubMed  Google Scholar 

  33. Yao M, Yao DF, Bian YZ, Zhang CG, Qiu LW, Wu W, et al. Oncofetal antigen glypican-3 as a promising early diagnostic marker for hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 2011;10:289–94.

    Article  CAS  Google Scholar 

  34. Nakatsura T, Yoshitake Y, Senju S, Monji M, Komori H, Motomura Y, et al. Glypican-3, overexpressed specifically in human hepatocellular carcinoma, is a novel tumor marker. Biochem Biophys Res Commun. 2003;306:16–25.

    Article  CAS  Google Scholar 

  35. Beale G, Chattopadhyay D, Gray J, et al. AFP, PIVKA III, GP3, SCCA and follisation as surveillance biomarkers for hepatocellular cancer in non-alcoholic and alcoholic fatty liver disease. BMC Cancer. 2008:8–200.

  36. Liu H, Li P, Zhai Y, Qu CF, Zhang LJ, Tan YF, et al. Diagnostic value of glypican-3 in serum and liver for primary hepatocellular carcinoma. World J Gastroenterol. 2010;16(35):4410–5.

    Article  CAS  Google Scholar 

  37. Xu D, Su C, Sun L, et al. Performance of serum Glypican 3 in diagnosis of hepatocellular carcinoma: a meta-analysis. Ann Hepatol. 2018;18(1):58–67. https://doi.org/10.5604/01.3001.0012.7863.

    Article  Google Scholar 

  38. Tahon AM, El-Ghanam MZ, Zaky S, et al. Significance of Glypican-3 in early detection of hepatocellular carcinoma in cirrhotic patients. J Gastrointest Cancer. 2018. https://doi.org/10.1007/s12029-018-0095-2.

    Article  Google Scholar 

  39. Maurel M, Dejeans N, Taouji S, Chevet E, Grosset CF. MicroRNA-1291-mediated silencing of IRE1α enhances Glypican-3 expression. RNA. 2013;19(6):778–88.

    Article  CAS  Google Scholar 

  40. Yamasaki T, Seki N, Yoshino H, Itesako T, Yamada Y, Tatarano S, et al. Tumor-suppressive microRNA-1291 directly regulates glucose transporter 1 in renal cell carcinoma. Cancer Sci. 2013;104(11):1411–9.

    Article  CAS  Google Scholar 

  41. Luo H, Guo W, Wang F, et al. MiR-1291 targets mucin 1 inhibiting cell proliferation and invasion to promote cell apoptosis in esophageal squamous cell carcinoma. Oncol Rep. 2015;34:2665–73.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinical Pathology Department, National Live Institute (NLI), Menufyia University, Sheben-Elkom, Egypt

    Neven A. Hagag & Ahmed A. Elsharawy

  2. Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), Sadat City University, Sadat City, Egypt

    Yasser B. M. Ali & Roba M. Talaat

  3. Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City, Abdel Moneim Riad St., Sadat City, Menufia, 32897, Egypt

    Roba M. Talaat

Authors
  1. Neven A. Hagag
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yasser B. M. Ali
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ahmed A. Elsharawy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Roba M. Talaat
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Study design: Roba and Neven; carry out the experiment: Neven; providing samples and collecting clinical data: Ahmed; analyzing and interpreting data: Neven and Yasser; writing manuscript: Roba and Neven; all authors read, revised, and approved the final document.

Corresponding author

Correspondence to Roba M. Talaat.

Ethics declarations

Statement of Ethics

The research institute’s committee has approved the study protocol on human research.

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hagag, N.A., Ali, Y.B.M., Elsharawy, A.A. et al. Clinical Impact of Circulated miR-1291 in Plasma of Patients with Liver Cirrhosis (LC) and Hepatocellular Carcinoma (HCC): Implication on Glypican-3 Expression. J Gastrointest Canc 51, 234–241 (2020). https://doi.org/10.1007/s12029-019-00234-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12029-019-00234-9

Keywords

Search

Navigation