EXPLORING MICRORNA EXPRESSION PATTERNS IN EARLY DETECTION AND PROGRESSION OF HEPATOCELLULAR CARCINOMA- SYSTEMATIC REVIEW

Authors

  • Irfan Ishaque Government College University, Lahore, Pakistan. Author
  • Murtaza Khodadadi Comsats University, Islamabad, Pakistan. Author
  • Hafsa Hameed Thakur Alpha Clinical Developments Ltd., USA. Author
  • Attiq Ullah Northeast Forestry University, Harbin, No 26, Hexing Road, Harbin 150040, P.R. China. Author
  • Amna Noor Rawalpindi Medical University, Rawalpindi, Pakistan. Author
  • Warda Jamal University of Haripur, Haripur, Pakistan Author
  • Mariyam Waheed Rawal Institute of Health Sciences, Islamabad, Pakistan Author
  • Summyya Rasheed BJ Microlabs, Rawalpindi, Pakistan. Author

DOI:

https://doi.org/10.71000/e94c6r69

Keywords:

Hepatocellular Carcinoma, microRNA, Biomarkers, Early Detection, Systematic Review, Diagnosis

Abstract

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with most cases diagnosed at an advanced stage due to limitations in current diagnostic tools. Traditional biomarkers such as alpha-fetoprotein lack the sensitivity and specificity needed for early detection. MicroRNAs (miRNAs) have emerged as promising molecular biomarkers, but evidence remains fragmented and inconsistent, highlighting the need for a systematic synthesis of current findings.

Objective: This systematic review aims to evaluate the diagnostic and prognostic value of specific microRNAs in the early detection and monitoring of hepatocellular carcinoma.

Methods: A systematic review was conducted following PRISMA guidelines. Literature searches were performed across PubMed, Scopus, Web of Science, and Cochrane Library for studies published between January 2019 and July 2024. Inclusion criteria encompassed observational and case-control studies assessing miRNA expression in HCC patients. Studies were screened independently by two reviewers, and data were extracted using a standardized form. Risk of bias was assessed using the Newcastle-Ottawa Scale. Due to heterogeneity in methodologies, a qualitative synthesis was performed.

Results: Eight studies involving 2,342 participants were included. Key miRNAs identified with strong diagnostic or prognostic relevance included miR-21, miR-122, miR-125b, miR-224, and exosomal miR-500a-3p. Reported sensitivities ranged from 72% to 85%, with area under the curve (AUC) values up to 0.91. Many miRNAs correlated significantly with tumor stage, recurrence, and survival outcomes. Risk of bias was generally low to moderate across included studies.

Conclusion: MicroRNAs show substantial potential as non-invasive biomarkers for the early diagnosis and monitoring of HCC. However, variability in detection methods and limited population diversity call for further large-scale, standardized studies to confirm their clinical applicability.

Author Biographies

  • Irfan Ishaque, Government College University, Lahore, Pakistan.

    Department of Zoology, Government College University, Lahore, Pakistan.

  • Murtaza Khodadadi , Comsats University, Islamabad, Pakistan.

    4th semester MSc Microbiology and Immunology, Comsats University, Islamabad, Pakistan.

  • Hafsa Hameed Thakur , Alpha Clinical Developments Ltd., USA.

     MSc. (UK), BSc. (UK), Research Scientist, Alpha Clinical Developments Ltd., USA.

  • Attiq Ullah, Northeast Forestry University, Harbin, No 26, Hexing Road, Harbin 150040, P.R. China.

    PhD Cancer Biology, Northeast Forestry University, Harbin, No 26, Hexing Road, Harbin 150040, P.R. China.

  • Amna Noor , Rawalpindi Medical University, Rawalpindi, Pakistan.

    Coordinator, PhD Microbiology and Molecular Biology, Chemical and Molecular Pathology, Rawalpindi Medical University, Rawalpindi, Pakistan.

  • Warda Jamal , University of Haripur, Haripur, Pakistan

    University of Haripur, Haripur, Pakistan

  • Mariyam Waheed , Rawal Institute of Health Sciences, Islamabad, Pakistan

    MBBS Graduate, Rawal Institute of Health Sciences, Islamabad, Pakistan

  • Summyya Rasheed , BJ Microlabs, Rawalpindi, Pakistan.

    Research Officer, BJ Microlabs, Rawalpindi, Pakistan.

References

Zhu B, Gu S, Wu X, He W, Zhou H. Bioinformatics analysis of tumor-educated platelet microRNAs in patients with hepatocellular carcinoma. Biosci Rep. 2021;41(12).

Jia T, Wang L, Zhang W, Hu Y, Tuerxun K. circSOX4 Enhances Hepatocellular Carcinoma Progression via miR-218-5p/YY1 Signaling. Biomed Res Int. 2023;2023:3370440.

Zhang Y, Yao R, Li M, Fang C, Feng K, Chen X, et al. CircTTC13 promotes sorafenib resistance in hepatocellular carcinoma through the inhibition of ferroptosis by targeting the miR-513a-5p/SLC7A11 axis. Mol Cancer. 2025;24(1):32.

Wang L, Zhao J, Zhu C, Yang K, Zhu L, Liu Y. Construction of a ceRNA Network and Comprehensive Analysis of lncRNA in Hepatocellular Carcinoma. Genes (Basel). 2022;13(5).

Liu L, Zhang P, Sun S, Cao C, Song Z. Downregulation of microRNA-129-2 by Hepatitis B Virus Promotes Cell Proliferation in Hepatocellular Carcinoma. Ann Clin Lab Sci. 2024;54(5):643-51.

Ghosh S, Bhowmik S, Majumdar S, Goswami A, Chakraborty J, Gupta S, et al. The exosome encapsulated microRNAs as circulating diagnostic marker for hepatocellular carcinoma with low alpha-fetoprotein. Int J Cancer. 2020;147(10):2934-47.

Xia G, Xie Y, He Q. Hepatitis B Virus Affected Serum MicroRNA-203a Level in Hepatocellular Carcinoma. Clin Lab. 2021;67(3).

Su Q, Li W, Zhang X, Wu R, Zheng K, Zhou T, et al. Integrated Bioinformatics Analysis for the Screening of Hub Genes and Therapeutic Drugs in Hepatocellular Carcinoma. Curr Pharm Biotechnol. 2023;24(8):1035-58.

Fang Y, Zhang X, Huang H, Zeng Z. The interplay between noncoding RNAs and drug resistance in hepatocellular carcinoma: the big impact of little things. J Transl Med. 2023;21(1):369.

Zhao F, Tan F, Tang L, Du Z, Chen X, Yang Y, et al. Long Non-coding RNA DLGAP1-AS1 and DLGAP1-AS2: Two Novel Oncogenes in Multiple Cancers. Curr Med Chem. 2023;30(25):2822-34.

Hajizadeh M, Hajizadeh F, Ghaffarei S, Amin Doustvandi M, Hajizadeh K, Yaghoubi SM, et al. MicroRNAs and their vital role in apoptosis in hepatocellular carcinoma: miRNA-based diagnostic and treatment methods. Gene. 2023;888:147803.

Kim SS, Baek GO, Jung S, Lee D, Lee YB, Lee JH, et al. Diagnostic accuracy of circulating microRNAs for hepatocellular carcinoma: A systematic review and meta-analysis. Clin Mol Hepatol. 2023;29(2):210–21.

Zhang Y, Wang X, Xu B, Wang W, Liu C, Yang T, et al. Circulating miRNA-122 as a potential biomarker for diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol. 2021;45(3):101526.

Ahn EY, Choi YJ, Choi JH, Kim JK, Kim J, Lee KH, et al. Plasma miR-224 and miR-500a-3p as novel diagnostic and prognostic biomarkers for hepatocellular carcinoma. J Liver Cancer. 2020;20(1):37–44.

Zhuang Y, Shen L, Li H, Zhang J, Zhang W. Diagnostic value of serum miR-139-5p and its relationship with clinicopathological features of hepatocellular carcinoma. J Clin Lab Anal. 2022;36(1):e24162.

Liu H, Zhang W, Zou B, Wang J, Deng Y, Deng L, et al. miR-101 suppresses hepatocellular carcinoma progression via downregulating EZH2. J Transl Med. 2020;18:301.

Lee YS, Kim SY, Ko YH, Hong EK, Shin YW, Lee SH, et al. Serum microRNA-125b as a biomarker for early detection of hepatocellular carcinoma. Clin Mol Hepatol. 2019;25(4):399–408.

Yuan L, Wang J, Xiao H, Wu W, Zhai J, Yang Z, et al. Diagnostic and prognostic value of serum exosomal microRNAs in patients with hepatocellular carcinoma. J Cell Physiol. 2022;237(6):3124–34.

Zhang Y, Guo X, Xiong L, Li W, Dong J. miR-21 as a potential biomarker for early detection and prognosis prediction of hepatocellular carcinoma. Oncol Lett. 2021;21(2):104.

Li W, Jiang Y, Pan Q, Yang G. miR-29a-5p regulates the malignant biological process of liver cancer cells through ARID2 regulation of EMT. Adv Clin Exp Med. 2023;32(5):575-82.

Yang L, Wei C, Li Y, He X, He M. miR-224 is an early-stage biomarker of hepatocellular carcinoma with miR-224 and miR-125b as prognostic biomarkers. Biomark Med. 2020;14(15):1485-500.

Tonon F, Grassi C, Tierno D, Biasin A, Grassi M, Grassi G, et al. Non-Coding RNAs as Potential Diagnostic/Prognostic Markers for Hepatocellular Carcinoma. Int J Mol Sci. 2024;25(22).

Han Q, Wang M, Dong X, Wei F, Luo Y, Sun X. Non-coding RNAs in hepatocellular carcinoma: Insights into regulatory mechanisms, clinical significance, and therapeutic potential. Front Immunol. 2022;13:985815.

Zhu M, Gao S, Ren X. Role of miR-498 Combined with CREB1 in Apoptosis and Invasion of Hepatoma Cell Line. Comput Math Methods Med. 2022;2022:9621764.

Xia J, Zhao H, Edmondson JL, Koss B, Zhan F. Role of NEK2 in tumorigenesis and tumor progression. Trends Mol Med. 2025;31(1):79-93.

Downloads

Published

2025-08-20

How to Cite

1.
Ishaque I, Murtaza Khodadadi, Hafsa Hameed Thakur, Attiq Ullah, Amna Noor, Warda Jamal, et al. EXPLORING MICRORNA EXPRESSION PATTERNS IN EARLY DETECTION AND PROGRESSION OF HEPATOCELLULAR CARCINOMA- SYSTEMATIC REVIEW. IJHR [Internet]. 2025 Aug. 20 [cited 2025 Aug. 29];3(4 (Health and Allied):635-40. Available from: https://insightsjhr.com/index.php/home/article/view/1263