SpringerLink
Log in

Featured lncRNA-based signature for discriminating prognosis and progression of hepatocellular carcinoma

  • Human Genetics • Original Paper
  • Published:
Journal of Applied Genetics Aims and scope Submit manuscript

A Correction to this article was published on 19 February 2024

This article has been updated

Abstract

Long non-coding RNAs (lncRNAs) have been implicated in carcinogenesis and progression of hepatocellular carcinoma (HCC). This study aimed to identify a robust lncRNA signature for predicting the survival of HCC patients. We performed an integrated analysis of the lncRNA expression profiling in The Cancer Genome Atlas (TCGA)—liver hepatocellular carcinoma database to identify the prognosis-related lncRNA for the HCC. The HCC cohort was randomly divided into a training set (n = 250) and a testing set (n = 113). Following a two-step screening, we identified an 18-lncRNA signature risk score. The high-risk subgroups had significantly shorter survival time than the low-risk group in both the training set (P < 0.0001) and the testing set (P = 0.005). Stratification analysis revealed that the prognostic value of the lncRNA-based signature was independent of the tumor stage and pathologic stage. The area under the receiver operating characteristic curve (AUROC) of the 18-lncRNA signature risk score was 0.826 (95%CI, 0.764–0.888), 0.817 (95%CI, 0.759–0.876), and 0.799 (95%CI, 0.731–0.867) for 1-year, 3-year, and 5-year follow-up, respectively. Bioinformatics analyses indicated that the 18 lncRNA might mediate cell cycle, DNA replication processes, and canonical cancer-related pathways, in which MCM3AP-AS1 was a potential target for HCC. In conclusion, the 18-lncRNA signature was a robust predictive biomarker for the prognosis and progression of HCC.

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

Access this article

Log in via an institution

Price includes VAT (Canada)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Data availability

The datasets presented in this study can be found in online repositories.

Change history

References

  • Ahmad M, Weiswald LB, Poulain L, Denoyelle C, Meryet-Figuiere M (2023) Involvement of lncRNAs in cancer cells migration, invasion and metastasis: cytoskeleton and ECM crosstalk. J Exp Clin Cancer Res 42(1):173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Davalos V, Esteller M (2019) Disruption of long noncoding RNAs targets cancer hallmark pathways in lung tumorigenesis. Cancer Res 79(12):3028–3030

    Article  CAS  PubMed  Google Scholar 

  • Fatica A, Bozzoni I (2014) Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet 15(1):7–21

    Article  CAS  PubMed  Google Scholar 

  • Goh GB, Chang PE, Tan CK (2015) Changing epidemiology of hepatocellular carcinoma in Asia. Best Pract Res Clin Gastroenterol 29(6):919–928

    Article  PubMed  Google Scholar 

  • Grixti JM, Ayers D (2020) Long noncoding RNAs and their link to cancer. Noncoding RNA Res 5(2):77–82

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hsu CY, Hsia CY, Huang YH, Su CW, Lin HC, Pai JT et al (2012) Comparison of surgical resection and transarterial chemoembolization for hepatocellular carcinoma beyond the Milan criteria: a propensity score analysis. Ann Surg Oncol 19(3):842–849

    Article  PubMed  Google Scholar 

  • Huang Z, Zhou JK, Peng Y, He W, Huang C (2020) The role of long noncoding RNAs in hepatocellular carcinoma. Mol Cancer 19(1):77

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iyer MK, Niknafs YS, Malik R, Singhal U, Sahu A, Hosono Y et al (2015) The landscape of long noncoding RNAs in the human transcriptome. Nat Genet 47(3):199–208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lai H, Li Y, Zhang H, Hu J, Liao J, Su Y et al (2022) exoRBase 2.0: an atlas of mRNA, lncRNA and circRNA in extracellular vesicles from human biofluids. Nucleic Acids Res 50(D1):D118–D128

  • Lan L, Liang Z, Zhao Y, Mo Y (2020) LncRNA MCM3AP-AS1 inhibits cell proliferation in cervical squamous cell carcinoma by down-regulating miRNA-93. Biosci Rep 40(2):BSR20193794

  • Lee YR, Kim G, Tak WY, Jang SY, Kweon YO, Park JG et al (2019) Circulating exosomal noncoding RNAs as prognostic biomarkers in human hepatocellular carcinoma. Int J Cancer 144(6):1444–1452

    Article  CAS  PubMed  Google Scholar 

  • Llovet JM, Zucman-Rossi J, Pikarsky E, Sangro B, Schwartz M, Sherman M et al (2016) Hepatocellular Carcinoma Nat Rev Dis Primers 2:16018

    Article  PubMed  Google Scholar 

  • Nemeth K, Bayraktar R, Ferracin M, Calin GA (2023) Non-coding RNAs in disease: from mechanisms to therapeutics. Nat Rev Genet. https://doi.org/10.1038/s41576-023-00662-1

  • Pea A, Jamieson NB, Braconi C (2021) Biology and clinical application of regulatory RNAs in hepatocellular carcinoma. Hepatology 73(Suppl 1):38–48

    Article  CAS  PubMed  Google Scholar 

  • Pinto-Marques H, Cardoso J, Silva S, Neto JL, Goncalves-Reis M, Proenca D et al (2022) A gene expression signature to select hepatocellular carcinoma patients for liver transplantation. Ann Surg 276(5):868–874

    Article  PubMed  Google Scholar 

  • Schmitt AM, Chang HY (2016) Long noncoding RNAs in cancer pathways. Cancer Cell 29(4):452–463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song M, Zhong A, Yang J, He J, Cheng S, Zeng J et al (2019) Large-scale analyses identify a cluster of novel long noncoding RNAs as potential competitive endogenous RNAs in progression of hepatocellular carcinoma. Aging (albany NY) 11(22):10422–10453

    Article  CAS  PubMed  Google Scholar 

  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A et al (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71(3):209–249

    Article  PubMed  Google Scholar 

  • Ulitsky I, Bartel DP (2013) lincRNAs: genomics, evolution, and mechanisms. Cell 154(1):26–46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wallace MC, Preen D, Jeffrey GP, Adams LA (2015) The evolving epidemiology of hepatocellular carcinoma: a global perspective. Expert Rev Gastroenterol Hepatol 9(6):765–779

    Article  CAS  PubMed  Google Scholar 

  • Yan X, Hu Z, Feng Y, Hu X, Yuan J, Zhao SD et al (2015) Comprehensive genomic characterization of long non-coding RNAs across human cancers. Cancer Cell 28(4):529–540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yan J, Zhou C, Guo K, Li Q, Wang Z (2019) A novel seven-lncRNA signature for prognosis prediction in hepatocellular carcinoma. J Cell Biochem 120(1):213–223

    Article  CAS  PubMed  Google Scholar 

  • Zhao QJ, Zhang J, Xu L, Liu FF (2018) Identification of a five-long non-coding RNA signature to improve the prognosis prediction for patients with hepatocellular carcinoma. World J Gastroenterol 24(30):3426–3439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao Y, Teng H, Yao F, Yap S, Sun Y, Ma L (2020) Challenges and strategies in ascribing functions to long noncoding RNAs. Cancers (Basel) 12(6):1458

Download references

Funding

This study was supported by grants from National Natural Science Foundation (81702419).

Author information

Author notes

  1. Huiyuan Qiu and Bo Jiang contributed equally to this work.

Authors and Affiliations

  1. Medical School of Nantong University, Nantong, 226001, China

    Huiyuan Qiu, Yinqi Chen, Zhaoyi Lin, Wenjie Zheng & **aolei Cao

  2. Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China

    Huiyuan Qiu & Wenjie Zheng

  3. Department of Gastroenterology, Suqian First People’s Hospital, Suqian, Jiangsu, China

    Bo Jiang

Authors
  1. Huiyuan Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bo Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yinqi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhaoyi Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wenjie Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. **aolei Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

W.Z. and X.C. designed and supervised this study. H.Q., Z.L., and Y.C. conducted the analysis. H.Q. drafted the manuscript. B.J. performed the revision. All authors approved the final version of the manuscript.

Corresponding authors

Correspondence to Wenjie Zheng or **aolei Cao.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Communicated by: Ewa Ziętkiewicz

Publisher's Note

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

The original online version of this article was revised: The original article contains a spelling error in author name. The author “**anglei Cao” should read as “**aolei Cao”.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 646 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Qiu, H., Jiang, B., Chen, Y. et al. Featured lncRNA-based signature for discriminating prognosis and progression of hepatocellular carcinoma. J Appl Genetics 65, 355–366 (2024). https://doi.org/10.1007/s13353-024-00836-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13353-024-00836-5

Keywords

Search

Navigation