116
Views
0
CrossRef citations to date
0
Altmetric
ORIGINAL RESEARCH

Development and Validation of a Novel Nomogram Integrated with Hypoxic and Lactate Metabolic Characteristics for Prognosis Prediction in Hepatocellular Carcinoma

, ORCID Icon, , , , ORCID Icon, , , & show all
Pages 241-255 | Received 06 Nov 2023, Accepted 24 Jan 2024, Published online: 01 Feb 2024

References

  • Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–249. doi:10.3322/caac.21660
  • Badwei N. Hepatocellular carcinoma gene expression: the new era, where it goes? iLIVER. 2023;2(1):36–40. doi:10.1016/j.iliver.2022.12.001
  • Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021;7(1):6. doi:10.1038/s41572-020-00240-3
  • Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382(20):1894–1905. doi:10.1056/NEJMoa1915745
  • Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised Phase 3 non-inferiority trial. Lancet. 2018;391(10126):1163–1173. doi:10.1016/s0140-6736(18)30207-1
  • Llovet JM, Castet F, Heikenwalder M, et al. Immunotherapies for hepatocellular carcinoma. Nat Rev Clin Oncol. 2022;19(3):151–172. doi:10.1038/s41571-021-00573-2
  • Xia S, Pan Y, Liang Y, Xu J, Cai X. The microenvironmental and metabolic aspects of sorafenib resistance in hepatocellular carcinoma. EBioMedicine. 2020;51:102610. doi:10.1016/j.ebiom.2019.102610
  • Liu Y, Xun Z, Ma K, et al. Identification of a tumour immune barrier in the HCC microenvironment that determines the efficacy of immunotherapy. J Hepatol. 2023;78(4):770–782. doi:10.1016/j.jhep.2023.01.011
  • Sin SQ, Mohan CD, Goh RMW, et al. Hypoxia signaling in hepatocellular carcinoma: challenges and therapeutic opportunities. Cancer Metastasis Rev. 2022. doi:10.1007/s10555-022-10071-1
  • Zhuang Y, Liu K, He Q, Gu X, Jiang C, Wu J. Hypoxia signaling in cancer: implications for therapeutic interventions. MedComm. 2023;4(1):e203. doi:10.1002/mco2.203
  • Ling S, Shan Q, Zhan Q, et al. USP22 promotes hypoxia-induced hepatocellular carcinoma stemness by a HIF1α/USP22 positive feedback loop upon TP53 inactivation. Gut. 2020;69(7):1322–1334. doi:10.1136/gutjnl-2019-319616
  • Wu H, Wang T, Liu Y, et al. Mitophagy promotes sorafenib resistance through hypoxia-inducible ATAD3A dependent Axis. J Exp Clin Cancer Res. 2020;39(1):274. doi:10.1186/s13046-020-01768-8
  • Hu W, Zheng S, Guo H, et al. PLAGL2-EGFR-HIF-1/2α Signaling Loop Promotes HCC Progression and Erlotinib Insensitivity. Hepatology. 2021;73(2):674–691. doi:10.1002/hep.31293
  • Suthen S, Lim CJ, Nguyen PHD, et al. Hypoxia-driven immunosuppression by Treg and type-2 conventional dendritic cells in HCC. Hepatology. 2022;76(5):1329–1344. doi:10.1002/hep.32419
  • Zhang X, Li Y, Ma Y, et al. Yes-associated protein (YAP) binds to HIF-1α and sustains HIF-1α protein stability to promote hepatocellular carcinoma cell glycolysis under hypoxic stress. J Exp Clin Cancer Res. 2018;37(1):216. doi:10.1186/s13046-018-0892-2
  • Xu Y, Hao X, Ren Y, et al. Research progress of abnormal lactate metabolism and lactate modification in immunotherapy of hepatocellular carcinoma. Front Oncol. 2022;12:1063423. doi:10.3389/fonc.2022.1063423
  • Du D, Liu C, Qin M, et al. Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma. Acta Pharm Sin B. 2022;12(2):558–580. doi:10.1016/j.apsb.2021.09.019
  • Kotsiliti E. Lactylation and HCC progression. Nat Rev Gastroenterol Hepatol. 2023;20(3):131. doi:10.1038/s41575-023-00746-7
  • Xu C, Xia Y, Zhang BW, et al. Macrophages facilitate tumor cell PD-L1 expression via an IL-1β-centered loop to attenuate immune checkpoint blockade. MedComm. 2023;4(2):e242. doi:10.1002/mco2.242
  • Zhao Y, Li M, Yao X, et al. HCAR1/MCT1 regulates tumor ferroptosis through the lactate-mediated AMPK-SCD1 activity and its therapeutic implications. Cell Rep. 2020;33(10):108487. doi:10.1016/j.celrep.2020.108487
  • Pan L, Feng F, Wu J, et al. Demethylzeylasteral targets lactate by inhibiting histone lactylation to suppress the tumorigenicity of liver cancer stem cells. Pharmacol Res. 2022;181:106270. doi:10.1016/j.phrs.2022.106270
  • Gu J, Zhou J, Chen Q, et al. Tumor metabolite lactate promotes tumorigenesis by modulating MOESIN lactylation and enhancing TGF-β signaling in regulatory T cells. Cell Rep. 2022;39(12):110986. doi:10.1016/j.celrep.2022.110986
  • Liberzon A, Birger C, Thorvaldsdóttir H, Ghandi M, Mesirov JP, Tamayo P. The Molecular Signatures Database (MSigDB) hallmark gene set collection. Cell Syst. 2015;1(6):417–425. doi:10.1016/j.cels.2015.12.004
  • Lu Y, Yang A, Quan C, et al. A single-cell atlas of the multicellular ecosystem of primary and metastatic hepatocellular carcinoma. Nat Commun. 2022;13(1):4594. doi:10.1038/s41467-022-32283-3
  • Ma L, Heinrich S, Wang L, et al. Multiregional single-cell dissection of tumor and immune cells reveals stable lock-and-key features in liver cancer. Nat Commun. 2022;13(1):7533. doi:10.1038/s41467-022-35291-5
  • Miao YR, Zhang Q, Lei Q, et al. ImmuCellAI: a unique method for comprehensive T-cell subsets abundance prediction and its application in cancer immunotherapy. Adv Sci. 2020;7(7):1902880. doi:10.1002/advs.201902880
  • Fu J, Li K, Zhang W, et al. Large-scale public data reuse to model immunotherapy response and resistance. Genome Med. 2020;12(1):21. doi:10.1186/s13073-020-0721-z
  • Hugo W, Zaretsky JM, Sun L, et al. Genomic and transcriptomic features of response to anti-PD-1 therapy in metastatic melanoma. Cell. 2016;165(1):35–44. doi:10.1016/j.cell.2016.02.065
  • Maeser D, Gruener RF, Huang RS. oncoPredict: an R package for predicting in vivo or cancer patient drug response and biomarkers from cell line screening data. Brief Bioinform. 2021;22(6):bbab260.
  • Yang W, Soares J, Greninger P, et al. Genomics of Drug Sensitivity in Cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells. Nucleic Acids Res. 2013;41(Database issue):D955–D961. doi:10.1093/nar/gks1111
  • Gao X, Zhao C, Zhang N, et al. Genetic expression and mutational profile analysis in different pathologic stages of hepatocellular carcinoma patients. BMC Cancer. 2021;21(1):786. doi:10.1186/s12885-021-08442-y
  • Zuo Q, He J, Zhang S, et al. PPARγ coactivator-1α suppresses metastasis of hepatocellular carcinoma by inhibiting Warburg effect by PPARγ-dependent WNT/β-catenin/pyruvate dehydrogenase kinase isozyme 1 axis. Hepatology. 2021;73(2):644–660. doi:10.1002/hep.31280
  • Wang C, Dong L, Li X, et al. The PGC1α/NRF1-MPC1 axis suppresses tumor progression and enhances the sensitivity to sorafenib/doxorubicin treatment in hepatocellular carcinoma. Free Radic Biol Med. 2021;163:141–152. doi:10.1016/j.freeradbiomed.2020.11.035
  • Ruf B, Bruhns M, Babaei S, et al. Tumor-associated macrophages trigger MAIT cell dysfunction at the HCC invasive margin. Cell. 2023;186(17):3686–3705.e32. doi:10.1016/j.cell.2023.07.026
  • Healy K, Pavesi A, Parrot T, et al. Human MAIT cells endowed with HBV specificity are cytotoxic and migrate towards HBV-HCC while retaining antimicrobial functions. JHEP Rep. 2021;3(4):100318. doi:10.1016/j.jhepr.2021.100318
  • Faggioli F, Palagano E, Di Tommaso L, et al. B lymphocytes limit senescence-driven fibrosis resolution and favor hepatocarcinogenesis in mouse liver injury. Hepatology. 2018;67(5):1970–1985. doi:10.1002/hep.29636
  • Qin M, Wang D, Fang Y, et al. Current perspectives on B lymphocytes in the immunobiology of hepatocellular carcinoma. Front Oncol. 2021;11:647854. doi:10.3389/fonc.2021.647854
  • Yang C, Huang X, Li Y, Chen J, Lv Y, Dai S. Prognosis and personalized treatment prediction in TP53-mutant hepatocellular carcinoma: an in silico strategy towards precision oncology. Brief Bioinform. 2021;22(3):bbaa164.
  • Castillo-Rodríguez RA, Trejo-Solís C, Cabrera-Cano A, Gómez-Manzo S, Dávila-Borja VM. Hypoxia as a modulator of inflammation and immune response in cancer. Cancers. 2022;14(9):2291.
  • Chen L, Huang L, Gu Y, Cang W, Sun P, Xiang Y. Lactate-lactylation hands between metabolic reprogramming and immunosuppression. Int J Mol Sci. 2022;23(19):11943.
  • Ippolito L, Comito G, Parri M, et al. Lactate Rewires Lipid Metabolism and Sustains a Metabolic-Epigenetic Axis in Prostate Cancer. Cancer Res. 2022;82(7):1267–1282. doi:10.1158/0008-5472.Can-21-0914
  • Yang Z, Yan C, Ma J, et al. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma. Nat Metab. 2023;5(1):61–79. doi:10.1038/s42255-022-00710-w
  • Méndez-Blanco C, Fondevila F, Fernández-Palanca P, et al. Stabilization of hypoxia-inducible factors and BNIP3 promoter methylation contribute to acquired sorafenib resistance in human hepatocarcinoma cells. Cancers. 2019;11(12):1984.
  • Jin Z, Lu Y, Wu X, et al. The cross-talk between tumor cells and activated fibroblasts mediated by lactate/BDNF/TrkB signaling promotes acquired resistance to anlotinib in human gastric cancer. Redox Biol. 2021;46:102076. doi:10.1016/j.redox.2021.102076
  • Bao MH, Wong CC. Hypoxia, metabolic reprogramming, and drug resistance in liver cancer. Cells. 2021;10(7). doi:10.3390/cells10071715
  • Guan Q, Pan J, Ren N, Qiao C, Wei M, Li Z. Identification of novel lactate metabolism signatures and molecular subtypes for prognosis in hepatocellular carcinoma. Front Cell Dev Biol. 2022;10:960277. doi:10.3389/fcell.2022.960277
  • Zhang B, Tang B, Gao J, Li J, Kong L, Qin L. A hypoxia-related signature for clinically predicting diagnosis, prognosis and immune microenvironment of hepatocellular carcinoma patients. J Transl Med. 2020;18(1):342. doi:10.1186/s12967-020-02492-9
  • Zhu Y, Qin LX. Strategies for improving the efficacy of immunotherapy in hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 2022;21(5):420–429. doi:10.1016/j.hbpd.2022.08.003
  • Gu Y, Xu S, Wang Z, et al. When immunotherapy meets liver transplantation for hepatocellular carcinoma: a bumpy but promising road. Chin J Cancer Res. 2023;35(2):92–107. doi:10.21147/j.issn.1000-9604.2023.02.02
  • Qian Y, Yang T, Liang H, Deng M. Myeloid checkpoints for cancer immunotherapy. Chin J Cancer Res. 2022;34(5):460–482. doi:10.21147/j.issn.1000-9604.2022.05.07
  • Khan AA, Liu ZK, Xu X. Recent advances in immunotherapy for hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 2021;20(6):511–520. doi:10.1016/j.hbpd.2021.06.010
  • Yuan J, Xu L, Zhou J, Shen L. Application of immune checkpoint inhibitors in hepatobiliary cancers. iLIVER. 2022;1(1):43–48. doi:10.1016/j.iliver.2022.03.002
  • Xiong J, Wang QQ. Mechanisms and strategies to overcome immunotherapy resistance in hepatobiliary malignancies. Hepatobiliary Pancreat Dis Int. 2022;21(5):430–439. doi:10.1016/j.hbpd.2022.07.006
  • Yang R, Li Y, Wang H, Qin T, Yin X, Ma X. Therapeutic progress and challenges for triple negative breast cancer: targeted therapy and immunotherapy. Mol Biomed. 2022;3(1):8. doi:10.1186/s43556-022-00071-6