Log in

Exploring the Prognostic Features of Hepatocellular Carcinoma via Text Mining and Data Analysis

  • BIOINFORMATICS
  • Published:
Molecular Biology Aims and scope Submit manuscript

Abstract

Transcatheter arterial chemoembolization is one of the interventional treatments for hepatocellular carcinoma (HCC). This treatment is generally used for patients with intermediate to advanced hepatocellular carcinoma, and identifying the role of HCC-related genes can help improve the efficiency of transcatheter arterial chemoembolization. To investigate the role of HCC-related genes and to provide valid evidence for transcatheter arterial chemoembolization treatment, we performed a comprehensive bioinformatics analysis. Through text mining (“hepatocellular carcinoma”) and microarray data analysis (GSE104580), we obtained a standard gene set, which was followed by gene ontology and Kyoto Gene and Genome Encyclopedia analysis. The significant 8 genes clustered in protein-protein interactions network were chosen to be used in the follow-up analysis. Through survival analysis low expression of the key genes were found to be strongly associated with survival in HCC patients in this study. The correlation between the expression of the key genes and tumor immune infiltration was assessed by Pearson correlation analysis. As a result, 15 drugs targeting seven of the eight genes have been identified, and therefore can be considered as potential components for transcatheter arterial chemoembolization treatment of HCC.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Canada)

Instant access to the full article PDF.

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

Similar content being viewed by others

REFERENCES

  1. Ferlay J., Soerjomataram I., Dikshit R., Eser S., Mathers C., Rebelo M., Parkin D.M., Forman D., Bray F. 2015. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer. 136, E359‒386.

    Article  CAS  PubMed  Google Scholar 

  2. Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. 2018. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68, 394‒424.

    Article  PubMed  Google Scholar 

  3. Coulon S., Heindryckx F., Geerts A., Van Steenkiste C., Colle I., Van Vlierberghe H. 2011. Angiogenesis in chronic liver disease and its complications. Liver Int. 31, 146‒162.

    Article  CAS  PubMed  Google Scholar 

  4. Chidambaranathan-Reghupaty S., Fisher P.B., Sarkar D. 2021. Hepatocellular carcinoma (HCC): Epidemiology, etiology and molecular classification. Adv. Cancer Res. 149, 1‒61.

    Article  PubMed  Google Scholar 

  5. Chen Z., **e H., Hu M., Huang T., Hu Y., Sang N., Zhao Y. 2020. Recent progress in treatment of hepatocellular carcinoma. Am. J. Cancer Res. 10, 2993‒3036.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Luo W., Zhang Y., He G., Yu M., Zheng M., Liu L., Zhou X. 2017. Effects of radiofrequency ablation versus other ablating techniques on hepatocellular carcinomas: a systematic review and meta-analysis. World J. Surg. Oncol. 15, 126.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Chang Y., Jeong S.W., Young Jang J., Jae Kim Y. 2020. Recent updates of transarterial chemoembolilzation in hepatocellular carcinoma. Int. J. Mol. Sci. 21 (21), 8165.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sacco R., Tapete G., Simonetti N., Sellitri R., Natali V., Melissari S., Cabibbo G., Biscaglia L., Bresci G., Giacomelli L. 2017. Transarterial chemoembolization for the treatment of hepatocellular carcinoma: A review. J. Hepatocell. Carcinoma. 4, 105‒110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lencioni R., De Baere T., Soulen M.C., Rilling W.S., Geschwind J.F. 2016. Lipiodol transarterial chemoembolization for hepatocellular carcinoma: A systematic review of efficacy and safety data. Hepatology. 64, 106‒116.

    Article  CAS  PubMed  Google Scholar 

  10. Wang J.H., Zhao L.F., Wang H.F., Wen Y.T., Jiang K.K., Mao X.M., Zhou Z.Y., Yao K.T., Geng Q.S., Guo D., Huang Z.X. 2019. GenCLiP 3: Mining human genes' functions and regulatory networks from PubMed based on co-occurrences and natural language processing. Bioinformatics. btz807.

  11. Barrett T., Troup D.B., Wilhite S.E., Ledoux P., R-udnev D., Evangelista C., Kim I.F., Soboleva A., Tomashevsky M., Marshall K.A., Phillippy K.H., Sherman P.M., Muertter R.N., Edgar R. 2009. NCBI GEO: Archive for high-throughput functional genomic data. Nucleic Acids Res. 37, D885‒D890.

    Article  CAS  PubMed  Google Scholar 

  12. Larriba Y., Rueda C., Fernández M.A., Peddada S.D. 2019. Microarray data normalization and robust detection of rhythmic features. Methods Mol. Biol. 1986, 207‒225.

    Article  CAS  PubMed  Google Scholar 

  13. Wan Z., Zhao B., Zhang X., Zhao Y. 2020. Drug discovery in cardiovascular disease identified by text mining and data analysis. Ann. Palliat. Med. 9, 3089‒3099.

    Article  PubMed  Google Scholar 

  14. Huang Da W., Sherman B.T., Lempicki R.A. 2009. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4, 44‒57.

    Article  PubMed  Google Scholar 

  15. Szklarczyk D., Gable A.L., Nastou K.C., Lyon D., Kirsch R., Pyysalo S., Doncheva N.T., Legeay M., Fang T., Bork P., Jensen L.J., Von Mering C. 2021. The STRING database in 2021: Customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res. 49, D605‒D612.

    Article  CAS  PubMed  Google Scholar 

  16. Bader G.D., Hogue C.W. 2003. An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinf. 4, 2.

    Article  Google Scholar 

  17. Tang Z., Li C., Kang B., Gao G., Li C., Zhang Z. 2017. GEPIA: A web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Aci-ds Res. 45, W98–W102.

    Article  CAS  Google Scholar 

  18. Huang T., Ye W., Lin X. 2021. Alternative splicing events in immune infiltration of lung adenocarcinoma. Med. Sci. Monit. 27, e934491.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Zhang Z., Lin E., Zhuang H., **e L., Feng X., Liu J., Yu Y. 2020. Construction of a novel gene-based model for prognosis prediction of clear cell renal cell carcinoma. Cancer Cell Int. 20, 27.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Li T., Fan J., Wang B., Traugh N., Chen Q., Liu J.S., Li B., Liu X.S. 2017. TIMER: A Web server for comprehensive analysis of tumor-infiltrating immune cells. Cancer Res. 77, e108‒e110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Griffith M., Griffith O.L., Coffman A.C., Weible J.V., Mcmichael J.F., Spies N.C., Koval J., Das I., Callaway M.B., Eldred J.M., Miller C.A., Subramanian J., Govindan R., Kumar R.D., Bose R., Ding L., Walker J.R., Larson D.E., Dooling D.J., Smith S.M., Ley T.J., Mardis E.R., Wilson R.K. 2013. DGIdb: Mining the druggable genome. Nat. Methods. 10, 1209‒1210.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Freshour S.L., Kiwala S., Cotto K.C., Coffman A.C., Mcmichael J.F., Song J.J., Griffith M., Griffith O.L., Wagner A.H. 2021. Integration of the Drug-Gene Interaction Database (DGIdb 4.0) with open crowdsource efforts. Nucleic Acids Res. 49, D1144‒D1151.

    Article  CAS  PubMed  Google Scholar 

  23. Silva J.P., Berger N.G., Tsai S., Christians K.K., Clarke C.N., Mogal H., White S., Rilling W., Gamblin T.C. 2017. Transarterial chemoembolization in hepatocellular carcinoma with portal vein tumor thrombosis: a systematic review and meta-analysis. HPB (Oxford). 19, 659‒666.

    Article  PubMed  Google Scholar 

  24. Ellery P.E., Maroney S.A., Cooley B.C., Luyendyk J.P., Zogg M., Weiler H., Mast A.E. 2015. A balance between TFPI and thrombin-mediated platelet activation is required for murine embryonic development. Blood. 125, 4078‒4084.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Morse M.A., Sun W., Kim R., He A.R., Abada P.B., Mynderse M., Finn R.S. 2019. The role of angiogenesis in hepatocellular carcinoma. Clin. Cancer Res. 25, 912‒920.

    Article  CAS  PubMed  Google Scholar 

  26. Kubala M.H., Declerck Y.A. 2019. The plasminogen activator inhibitor-1 paradox in cancer: A mechanistic understanding. Cancer Metastasis Rev. 38, 483‒492.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Carmeliet P., Stassen J.M., Schoonjans L., Ream B., Van Den Oord J.J., De Mol M., Mulligan R.C., Collen D. 1993. Plasminogen activator inhibitor-1 gene-deficient mice. II. Effects on hemostasis, thrombosis, and thrombolysis. J. Clin. Invest. 92, 2756‒2760.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Marquard S., Thomann S., Weiler S.M.E., Bissinger M., Lutz T., Sticht C., Toth M., De La Torre C., Gretz N., Straub B.K., Marquardt J., Schirmacher P., Breuhahn K. 2020. Yes-associated protein (YAP) induces a secretome phenotype and transcriptionally regulates plasminogen activator Inhibitor-1 (PAI-1) expression in hepatocarcinogenesis. Cell Commun. Signal. 18, 166.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Ma T., Jayaraman S., Wang K.S., Song Y., Yang B., Li J., Bastidas J.A., Verkman A.S. 2001. Defective dietary fat processing in transgenic mice lacking aquaporin-1 water channels. Am. J. Physiol. Cell Physiol. 280 (1), C126‒C134.

    Article  CAS  PubMed  Google Scholar 

  30. Li L., Zhang H., Ma T., Verkman A.S. 2009. Very high aquaporin-1 facilitated water permeability in mouse gallbladder. Am. J. Physiol. Gastrointest. Liver Physiol. 296, G816‒G822.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Nico B., Ribatti D. 2010. Aquaporins in tumor growth and angiogenesis. Cancer Lett. 294, 135‒138.

    Article  CAS  PubMed  Google Scholar 

  32. Luo L.M., **a H., Shi R., Zeng J., Liu X.R., Wei M. 2017. The association between aquaporin-1 expression, microvessel density and the clinicopathological features of hepatocellular carcinoma. Oncol. Lett. 14, 7077‒7084.

    PubMed  PubMed Central  Google Scholar 

  33. Anthony T.L., Brooks H.L., Boassa D., Leonov S., Yanochko G.M., Regan J.W., Yool A.J. 2000. Cloned human aquaporin-1 is a cyclic GMP-gated ion channel. Mol. Pharmacol. 57, 576‒588.

    Article  CAS  PubMed  Google Scholar 

  34. De Ieso M.L., Pei J.V., Nourmohammadi S., Smith E., Chow P.H., Kourghi M., Hardingham J.E., Yool A.J. 2019. Combined pharmacological administration of AQP1 ion channel blocker AqB011 and water channel blocker Bacopaside II amplifies inhibition of colon cancer cell migration. Sci. Rep. 9, 12635.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Jiang Y. 2009. Aquaporin-1 activity of plasma membrane affects HT20 colon cancer cell migration. IUBMB Life. 61, 1001‒1009.

    Article  CAS  PubMed  Google Scholar 

  36. **ong X.X., Qiu X.Y., Hu D.X., Chen X.Q. 2017. Advances in hypoxia-mediated mechanisms in hepatocellular carcinoma. Mol. Pharmacol. 92, 246‒255.

    Article  CAS  PubMed  Google Scholar 

  37. Yang L., Zhang Z., Sun Y., Pang S., Yao Q., Lin P., Cheng J., Li J., Ding G., Hui L., Li Y., Li H. 2020. Integrative analysis reveals novel driver genes and molecular subclasses of hepatocellular carcinoma. Aging (Albany NY). 12 (23), 23849‒23871.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Xu C., Sun L., Jiang C., Zhou H., Gu L., Liu Y., Xu Q. 2017. SPP1, analyzed by bioinformatics methods, promotes the metastasis in colorectal cancer by activating EMT pathway. Biomed. Pharmacother. 91, 1167‒1177.

    Article  CAS  PubMed  Google Scholar 

  39. Peng Y., Liu C., Li M., Li W., Zhang M., Jiang X., Chang Y., Liu L., Wang F., Zhao Q. 2021. Identification of a prognostic and therapeutic immune signature associated with hepatocellular carcinoma. Cancer Cell Int. 21, 98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Liu L., Zhang R., Deng J., Dai X., Zhu X., Fu Q., Zhang H., Tong Z., Zhao P., Fang W., Zheng Y., Bao X. 2022. Construction of TME and identification of crosstalk between malignant cells and macrophages by SPP1 in hepatocellular carcinoma. Cancer Immunol. Immunother. 71, 121‒136.

    Article  CAS  PubMed  Google Scholar 

  41. Wang J., Hao F., Fei X., Chen Y. 2019. SPP1 functions as an enhancer of cell growth in hepatocellular carcinoma targeted by miR-181c. Am. J. Transl. Res. 11, 6924‒6937.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Boycott C., Beetch M., Yang T., Lubecka K., Ma Y., Zhang J., Kurzava Kendall L., Ullmer M., Ramsey B.S., Torregrosa-Allen S., Elzey B.D., Cox A., Lanman N.A., Hui A., Villanueva N., De Conti A., Huan T., Pogribny I., Stefanska B. 2022. Epigenetic aberrations of gene expression in a rat model of hepatocellular carcinoma. Epigenetics. 17 (11), 1513‒1534.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Pelagalli A., Nardelli A., Fontanella R., Zannetti A. 2016. Inhibition of AQP1 hampers osteosarcoma and hepatocellular carcinoma progression mediated by bone marrow-derived mesenchymal stem cells. Int. J. Mol. Sci. 17 (7), 1102.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

ACKNOWLEDGMENTS

Thanks to Zhao’s team (Official Wechat Account: SCIPhD) of Sheng **n Zhu Shou for suggestions and grammarly editing on the article.

Funding

This research was funded by Minhang Hospital, Fudan University, Hospital-level Project (2022MHLC05), project title: SERPINE1 expression is regulated by YAP and TGF-β crosstalk in hepatocellular carcinoma.

Author information

Authors and Affiliations

Authors

Contributions

Z.H. Yang: Investigation, Conceptualization, Data curation, Formal analysis, Methodology, Software, Supervision, Validation, Visualization, Writing original draft, Writing review & editing. S.X. Wang: Data curation, Formal analysis, Methodology, Validation, Visualization, Writing review & editing.

Corresponding author

Correspondence to S. X. Wang.

Ethics declarations

COMPLIANCE WITH ETHICAL STANDARDS

All participated authors declare that they have no known competing financial interests or personal relationships that couldhave appeared to influence the work reported in this paper. This article does not contain any research involving humans or animals as subjects of research.

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are openly available in the NCBI-Gene Expression Omnibus database (NCBI-GEO) (website: https://www.ncbi.nlm. nih.gov/geo/query/acc.cgi?acc=GSE104580).

ADDITIONAL INFORMATION

The text was submitted by the author(s) in English.

Additional information

Abbreviations: HCC, hepatocellular carcinoma; BCLC, Barcelona Clinical Hepatocellular Carcinoma; LT, liver transplantation; TACE, transcatheter arterial chemoembolization; HRGs, HCC-related genes; PPI, protein-protein interactions; TMGs, text mining genes; DEGs, differentially expressed genes; FC, fold change; GO, Gene Ontology; BP, biological process; CC, cellular component; MF, molecular function; OS, overall survival; AUC, area under the curve; TIMER, Tumor IMmune Estimation Resource; TAM, tumor-associated macrophages.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, Z.H., Wang, S.X. Exploring the Prognostic Features of Hepatocellular Carcinoma via Text Mining and Data Analysis. Mol Biol 57, 530–543 (2023). https://doi.org/10.1134/S0026893323030160

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0026893323030160

Keywords:

Navigation