Download PDF
Horm Metab Res
DOI: 10.1055/a-2314-0988
Original Article: Endocrine Research

Identification and Verification of a Glycolysis-Related lncRNA Prognostic Signature for Hepatocellular Carcinoma

Fakai Qiu
1   Minimally Invasive Interventional Division, Shaanxi Provincial Cancer Hospital, Xi’an, China
,
Guozheng Yu
1   Minimally Invasive Interventional Division, Shaanxi Provincial Cancer Hospital, Xi’an, China
,
Mei Li
1   Minimally Invasive Interventional Division, Shaanxi Provincial Cancer Hospital, Xi’an, China
,
Zhubin Li
1   Minimally Invasive Interventional Division, Shaanxi Provincial Cancer Hospital, Xi’an, China
,
Qinyang Zhang
1   Minimally Invasive Interventional Division, Shaanxi Provincial Cancer Hospital, Xi’an, China
,
Xudong Mu
1   Minimally Invasive Interventional Division, Shaanxi Provincial Cancer Hospital, Xi’an, China
,
Yuan Cheng
1   Minimally Invasive Interventional Division, Shaanxi Provincial Cancer Hospital, Xi’an, China
,
Pengtao Zhai
1   Minimally Invasive Interventional Division, Shaanxi Provincial Cancer Hospital, Xi’an, China
,
Qunyi Liu
1   Minimally Invasive Interventional Division, Shaanxi Provincial Cancer Hospital, Xi’an, China
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Abstract

Hepatocellular carcinoma (HCC) is a primary liver cancer with a high mortality rate. The search for a new biomarker could help the prognosis of HCC patients. We identified the glycolytic gene set associated with HCC and the glycolytic lncRNA based on TCGA and MsigDB databases. According to these lncRNAs, K-means clustering, and regression analysis were performed on the patients. Two groups of HCC patients with different lncRNA expression levels were obtained based on K-means clustering results. The results of difference analysis and enrichment analysis showed that DEmRNA in the two HCC populations with significant survival differences was mainly enriched in transmembrane transporter complex, RNA polymerase II specificity, cAMP signaling pathway, and calcium signaling pathway. In addition, a prognostic model of HCC with 4 DElncRNAs was constructed based on regression analysis. ROC curve analysis showed that the model had good predictive performance. Drug predictionresults showed that the efficacy of JQ1, niraparib, and teniposide was higher in the low-risk group than in the high-risk group. In conclusion, this study preliminarily identified glycolytic-related prognostic features of lncRNAs in HCC and constructed a risk assessment model. The results of this study are expected to guide the prognosis assessment of clinical HCC patients.

Keywords

hepatocellular carcinoma - glycolysis - nonnegative matrix factorization - K-means - random forests - prognostic signature

Supplementary Material



Publication History

Received: 22 January 2024

Accepted after revision: 22 April 2024

Article published online:
21 May 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin 2020; 70: 7-30
    CrossrefPubMedGoogle Scholar
  • 2 Bray F, Ferlay J, Soerjomataram I. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394-424
    CrossrefPubMedGoogle Scholar
  • 3 Ligat G, Schuster C, Baumert TF. Hepatitis B virus core variants, liver fibrosis, and hepatocellular carcinoma. Hepatology 2019; 69: 5-8
    CrossrefPubMedGoogle Scholar
  • 4 Jemal A, Bray F, Center MM. et al. Global cancer statistics. CA Cancer J Clin 2011; 61: 69-90
    CrossrefPubMedGoogle Scholar
  • 5 Anwanwan D, Singh SK, Singh S. et al. Challenges in liver cancer and possible treatment approaches. Biochim Biophys Acta Rev Cancer 2020; 1873: 188314
    CrossrefPubMedGoogle Scholar
  • 6 Dufour JF, Bargellini I, De Maria N. et al. Intermediate hepatocellular carcinoma: current treatments and future perspectives. Ann Oncol 2013; 24: ii24-ii29
    CrossrefPubMedGoogle Scholar
  • 7 Paul S, Ghosh S, Kumar S. Tumor glycolysis, an essential sweet tooth of tumor cells. Semin Cancer Biol 2022; 86: 1216-1230
    CrossrefPubMedGoogle Scholar
  • 8 Zhang H, Su X, Burley SK. et al. mTOR regulates aerobic glycolysis through NEAT1 and nuclear paraspeckle-mediated mechanism in hepatocellular carcinoma. Theranostics 2022; 12: 3518-3533
    CrossrefPubMedGoogle Scholar
  • 9 Ganapathy-Kanniappan S, Geschwind JF. Tumor glycolysis as a target for cancer therapy: progress and prospects. Mol Cancer 2013; 12: 152
    CrossrefPubMedGoogle Scholar
  • 10 Wang S, Zhou L, Ji N. et al. Targeting ACYP1-mediated glycolysis reverses lenvatinib resistance and restricts hepatocellular carcinoma progression. Drug Resist Updat 2023; 69: 100976
    CrossrefPubMedGoogle Scholar
  • 11 Suk FM, Wu CY, Fang CC. et al. beta-HB treatment reverses sorafenib resistance by shifting glycolysis-lactate metabolism in HCC. Biomed Pharmacother 2023; 166: 115293
    CrossrefPubMedGoogle Scholar
  • 12 Wang Y, Lu JH, Wu QN. et al. LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer. Mol Cancer 2019; 18: 174
    CrossrefPubMedGoogle Scholar
  • 13 Chen F, Chen J, Yang L. et al. Extracellular vesicle-packaged HIF-1alpha-stabilizing lncRNA from tumour-associated macrophages regulates aerobic glycolysis of breast cancer cells. Nat Cell Biol 2019; 21: 498-510
    CrossrefPubMedGoogle Scholar
  • 14 Fei M, Li X, Liang S. et al. LncRNA PWRN1 inhibits the progression of hepatocellular carcinoma by activating PKM2 activity. Cancer Lett 2024; 584: 216620
    CrossrefPubMedGoogle Scholar
  • 15 Tang J, Yan T, Bao Y. et al. LncRNA GLCC1 promotes colorectal carcinogenesis and glucose metabolism by stabilizing c-Myc. Nat Commun 2019; 10: 3499
    CrossrefPubMedGoogle Scholar
  • 16 Zhang C, Wang H, Liu Q. et al. LncRNA CCAT1 facilitates the progression of gastric cancer via PTBP1-mediated glycolysis enhancement. J Exp Clin Cancer Res 2023; 42: 246
    CrossrefPubMedGoogle Scholar
  • 17 Li X, Zhao Q, Qi J. et al. lncRNA Ftx promotes aerobic glycolysis and tumor progression through the PPARgamma pathway in hepatocellular carcinoma. Int J Oncol 2018; 53: 551-566
    PubMedGoogle Scholar
  • 18 Gaujoux R, Seoighe C. A flexible R package for nonnegative matrix factorization. BMC Bioinformatics 2010; 11: 367
    CrossrefPubMedGoogle Scholar
  • 19 Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 2010; 26: 139-140
    CrossrefPubMedGoogle Scholar
  • 20 Zhang H, Meltzer P, Davis S. RCircos: an R package for Circos 2D track plots. BMC Bioinformatics 2013; 14: 244
    CrossrefPubMedGoogle Scholar
  • 21 Wilkerson MD, Hayes DN. ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking. Bioinformatics 2010; 26: 1572-1573
    CrossrefPubMedGoogle Scholar
  • 22 Yu G, Wang LG, Han Y. et al. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 2012; 16: 284-287
    CrossrefPubMedGoogle Scholar
  • 23 Blanche P, Dartigues JF, Jacqmin-Gadda H. Estimating and comparing time-dependent areas under receiver operating characteristic curves for censored event times with competing risks. Stat Med 2013; 32: 5381-5397
    CrossrefPubMedGoogle Scholar
  • 24 Feng J, Li J, Wu L. et al. Emerging roles and the regulation of aerobic glycolysis in hepatocellular carcinoma. J Exp Clin Cancer Res 2020; 39: 126
    CrossrefPubMedGoogle Scholar
  • 25 Belizario JE, Sangiuliano BA, Perez-Sosa M. et al. Using pharmacogenomic databases for discovering patient-target genes and small molecule candidates to cancer therapy. Front Pharmacol 2016; 7: 312
    CrossrefPubMedGoogle Scholar
  • 26 Hsu CC, Wu LC, Hsia CY. et al. Energy metabolism determines the sensitivity of human hepatocellular carcinoma cells to mitochondrial inhibitors and biguanide drugs. Oncol Rep 2015; 34: 1620-1628
    CrossrefPubMedGoogle Scholar
  • 27 Shen SN, Li K, Liu Y. et al. Down-regulation of long noncoding RNA PVT1 inhibits esophageal carcinoma cell migration and invasion and promotes cell apoptosis via microRNA-145-mediated inhibition of FSCN1. Mol Oncol 2019; 13: 2554-2573
    CrossrefPubMedGoogle Scholar
  • 28 Miao H, Wang L, Zhan H. et al. A long noncoding RNA distributed in both nucleus and cytoplasm operates in the PYCARD-regulated apoptosis by coordinating the epigenetic and translational regulation. PLoS Genet 2019; 15: e1008144
    CrossrefPubMedGoogle Scholar
  • 29 Wang F, Hu Y, Wang H. et al. LncRNA FTO-IT1 promotes glycolysis and progression of hepatocellular carcinoma through modulating FTO-mediated N6-methyladenosine modification on GLUT1 and PKM2. J Exp Clin Cancer Res 2023; 42: 267
    CrossrefPubMedGoogle Scholar
  • 30 Yano S, Tazawa H, Kagawa S. et al. FUCCI real-time cell-cycle imaging as a guide for designing improved cancer therapy: a review of innovative strategies to target quiescent chemo-resistant cancer cells. Cancers (Basel) 2020; 12: 2655
    CrossrefPubMedGoogle Scholar
  • 31 Dellino GI, Palluzzi F, Chiariello AM. et al. Release of paused RNA polymerase II at specific loci favors DNA double-strand-break formation and promotes cancer translocations. Nat Genet 2019; 51: 1011-1023
    CrossrefPubMedGoogle Scholar
  • 32 Aparicio T, Baer R, Gautier J. DNA double-strand break repair pathway choice and cancer. DNA Repair (Amst) 2014; 19: 169-175
    CrossrefPubMedGoogle Scholar
  • 33 Zhang X, Chiang HC, Wang Y. et al. Attenuation of RNA polymerase II pausing mitigates BRCA1-associated R-loop accumulation and tumorigenesis. Nat Commun 2017; 8: 15908
    CrossrefPubMedGoogle Scholar
  • 34 Tang C, Liu D, Fan Y. et al. Visualization and bibliometric analysis of cAMP signaling system research trends and hotspots in cancer. J Cancer 2021; 12: 358-370
    CrossrefPubMedGoogle Scholar
  • 35 Monteith GR, Prevarskaya N, Roberts-Thomson SJ. The calcium-cancer signalling nexus. Nat Rev Cancer 2017; 17: 367-380
    CrossrefPubMedGoogle Scholar
  • 36 Di J, Huang H, Qu D. et al. Rap2B promotes proliferation, migration, and invasion of human breast cancer through calcium-related ERK1/2 signaling pathway. Sci Rep 2015; 5: 12363
    CrossrefPubMedGoogle Scholar
  • 37 Liu Y, Zhu J, Ma X. et al. ceRNA network construction and comparison of gastric cancer with or without Helicobacter pylori infection. J Cell Physiol 2019; 234: 7128-7140
    CrossrefPubMedGoogle Scholar
  • 38 Li Y, Zhao Z, Liu W. et al. SNHG3 functions as miRNA sponge to promote breast cancer cells growth through the metabolic reprogramming. Appl Biochem Biotechnol 2020; 191: 1084-1099
    CrossrefPubMedGoogle Scholar
  • 39 Zhang G, Ma A, Jin Y. et al. LncRNA SNHG16 induced by TFAP2A modulates glycolysis and proliferation of endometrial carcinoma through miR-490-3p/HK2 axis. Am J Transl Res 2019; 11: 7137-7145
    PubMedGoogle Scholar