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Published in: BMC Cancer 1/2024

Open Access 01-12-2024 | Hepatocellular Carcinoma | Research

G6PD and machine learning algorithms as prognostic and diagnostic indicators of liver hepatocellular carcinoma

Authors: Fei Li, Boshen Wang, Hao Li, Lu Kong, Baoli Zhu

Published in: BMC Cancer | Issue 1/2024

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Abstract

Background

Liver Hepatocellular carcinoma (LIHC) exhibits a high incidence of liver cancer with escalating mortality rates over time. Despite this, the underlying pathogenic mechanism of LIHC remains poorly understood.

Materials & methods

To address this gap, we conducted a comprehensive investigation into the role of G6PD in LIHC using a combination of bioinformatics analysis with database data and rigorous cell experiments. LIHC samples were obtained from TCGA, ICGC and GEO databases, and the differences in G6PD expression in different tissues were investigated by differential expression analysis, followed by the establishment of Nomogram to determine the percentage of G6PD in causing LIHC by examining the relationship between G6PD and clinical features, and the subsequent validation of the effect of G6PD on the activity, migration, and invasive ability of hepatocellular carcinoma cells by using the low expression of LI-7 and SNU-449. Additionally, we employed machine learning to validate and compare the predictive capacity of four algorithms for LIHC patient prognosis.

Results

Our findings revealed significantly elevated G6PD expression levels in liver cancer tissues as compared to normal tissues. Meanwhile, Nomogram and Adaboost, Catboost, and Gbdt Regression analyses showed that G6PD accounted for 46%, 31%, and 49% of the multiple factors leading to LIHC. Furthermore, we observed that G6PD knockdown in hepatocellular carcinoma cells led to reduced proliferation, migration, and invasion abilities. Remarkably, the Decision Tree C5.0 decision tree algorithm demonstrated superior discriminatory performance among the machine learning methods assessed.

Conclusion

The potential diagnostic utility of G6PD and Decision Tree C5.0 for LIHC opens up a novel avenue for early detection and improved treatment strategies for hepatocellular carcinoma.
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Literature
2.
go back to reference Henley SJ, Ward EM, Scott S, et al. Annual report to the nation on the status of cancer, part I: national cancer statistics. Cancer. 2020;126(10):2225–49.CrossRefPubMed Henley SJ, Ward EM, Scott S, et al. Annual report to the nation on the status of cancer, part I: national cancer statistics. Cancer. 2020;126(10):2225–49.CrossRefPubMed
3.
go back to reference Llovet JM, Castet F, Heikenwalder M, et al. Immunotherapies for hepatocellular carcinoma. Nat Rev Clin Oncol. 2022;19(3):151–72.CrossRefPubMed Llovet JM, Castet F, Heikenwalder M, et al. Immunotherapies for hepatocellular carcinoma. Nat Rev Clin Oncol. 2022;19(3):151–72.CrossRefPubMed
4.
go back to reference Yin ZY, Li XW. Immunotherapy for hepatocellular carcinoma. Cancer Lett. 2020;470:8–17.CrossRef Yin ZY, Li XW. Immunotherapy for hepatocellular carcinoma. Cancer Lett. 2020;470:8–17.CrossRef
6.
go back to reference Chen XY, Xu ZJ, Zhu ZJ, et al. Modulation of G6PD affects bladder cancer via ROS accumulation and the AKT pathway in vitro. Int J Oncol. 2018;53(4):1703–12.PubMed Chen XY, Xu ZJ, Zhu ZJ, et al. Modulation of G6PD affects bladder cancer via ROS accumulation and the AKT pathway in vitro. Int J Oncol. 2018;53(4):1703–12.PubMed
7.
go back to reference Forteleoni G, Argiolas L, Farris A, et al. G6PD deficiency and breast-cancer. Tumori. 1988;74(6):665–7.CrossRefPubMed Forteleoni G, Argiolas L, Farris A, et al. G6PD deficiency and breast-cancer. Tumori. 1988;74(6):665–7.CrossRefPubMed
8.
go back to reference Wang JX, Yuan WJ, Chen ZK, et al. Overexpression of G6PD is associated with poor clinical outcome in gastric cancer. Tumor Biol. 2012;33(1):95–101.CrossRef Wang JX, Yuan WJ, Chen ZK, et al. Overexpression of G6PD is associated with poor clinical outcome in gastric cancer. Tumor Biol. 2012;33(1):95–101.CrossRef
9.
go back to reference Baba M, Yamamoto R, Iishi H, et al. Role of glucose-6-phosphate-dehydrogenase on enhanced proliferation of pre-neoplastic and neoplastic-cells in rat-liver induced by n-nitrosomorpholine. Int J Cancer. 1989;43(5):892–5.CrossRefPubMed Baba M, Yamamoto R, Iishi H, et al. Role of glucose-6-phosphate-dehydrogenase on enhanced proliferation of pre-neoplastic and neoplastic-cells in rat-liver induced by n-nitrosomorpholine. Int J Cancer. 1989;43(5):892–5.CrossRefPubMed
10.
go back to reference Huang SG, Yang J, Fong S, et al. Artificial intelligence in cancer diagnosis and prognosis: opportunities and challenges. Cancer Lett. 2020;471:61–71.CrossRefPubMed Huang SG, Yang J, Fong S, et al. Artificial intelligence in cancer diagnosis and prognosis: opportunities and challenges. Cancer Lett. 2020;471:61–71.CrossRefPubMed
11.
go back to reference Feng SJ, Wang JH, Wang LH, et al. Current status and analysis of machine learning in hepatocellular carcinoma. J Clin Translatl Hepatol. 2023;11(5):1184–91. Feng SJ, Wang JH, Wang LH, et al. Current status and analysis of machine learning in hepatocellular carcinoma. J Clin Translatl Hepatol. 2023;11(5):1184–91.
12.
go back to reference Handelman GS, Kok HK, Chandra RV, et al. eDoctor: machine learning and the future of medicine. J Intern Med. 2018;284(6):603–19.CrossRefPubMed Handelman GS, Kok HK, Chandra RV, et al. eDoctor: machine learning and the future of medicine. J Intern Med. 2018;284(6):603–19.CrossRefPubMed
13.
go back to reference Maglogiannis I, Zafiropoulos E, Anagnostopoulos I. An intelligent system for automated breast cancer diagnosis and prognosis using SVM based classifiers. Appl Intell. 2009;30(1):24–36.CrossRef Maglogiannis I, Zafiropoulos E, Anagnostopoulos I. An intelligent system for automated breast cancer diagnosis and prognosis using SVM based classifiers. Appl Intell. 2009;30(1):24–36.CrossRef
14.
go back to reference Kuo RJ, Huang MH, Cheng WC, et al. Application of a two-stage fuzzy neural network to a prostate cancer prognosis system. Artif Intell Med. 2015;63(2):119–33.CrossRefPubMed Kuo RJ, Huang MH, Cheng WC, et al. Application of a two-stage fuzzy neural network to a prostate cancer prognosis system. Artif Intell Med. 2015;63(2):119–33.CrossRefPubMed
15.
go back to reference Peng JF, Chen C, Zhou M, et al. A Machine-learning approach to forecast aggravation risk in patients with acute exacerbation of chronic obstructive pulmonary disease with clinical indicators. Sci Rep. 2020;10(1):3118.CrossRefPubMedPubMedCentral Peng JF, Chen C, Zhou M, et al. A Machine-learning approach to forecast aggravation risk in patients with acute exacerbation of chronic obstructive pulmonary disease with clinical indicators. Sci Rep. 2020;10(1):3118.CrossRefPubMedPubMedCentral
16.
go back to reference Dore MP, Vidili G, Marras G, et al. Inverse association between glucose-6-phosphate dehydrogenase deficiency and hepatocellular carcinoma. Asian Pacific J Cancer Prevent. 2018;19(4):1069–73. Dore MP, Vidili G, Marras G, et al. Inverse association between glucose-6-phosphate dehydrogenase deficiency and hepatocellular carcinoma. Asian Pacific J Cancer Prevent. 2018;19(4):1069–73.
18.
go back to reference Cao F, Luo AG, Yang CW. G6PD inhibits ferroptosis in hepatocellular carcinoma by targeting cytochrome P450 oxidoreductase. Cellu Signal. 2021;87:110098.CrossRef Cao F, Luo AG, Yang CW. G6PD inhibits ferroptosis in hepatocellular carcinoma by targeting cytochrome P450 oxidoreductase. Cellu Signal. 2021;87:110098.CrossRef
19.
go back to reference Lu M, Lu L, Dong QZ, et al. Elevated G6PD expression contributes to migration and invasion of hepatocellular carcinoma cells by inducing epithelial-mesenchymal transition. Acta Biochim Biophys Sin. 2018;50(4):370–80.CrossRefPubMed Lu M, Lu L, Dong QZ, et al. Elevated G6PD expression contributes to migration and invasion of hepatocellular carcinoma cells by inducing epithelial-mesenchymal transition. Acta Biochim Biophys Sin. 2018;50(4):370–80.CrossRefPubMed
20.
go back to reference Li M, He XX, Guo WX, et al. Aldolase B suppresses hepatocellular carcinogenesis by inhibiting G6PD and pentose phosphate pathways. Nat Cancer. 2020;1(7):735-+.CrossRefPubMed Li M, He XX, Guo WX, et al. Aldolase B suppresses hepatocellular carcinogenesis by inhibiting G6PD and pentose phosphate pathways. Nat Cancer. 2020;1(7):735-+.CrossRefPubMed
21.
go back to reference Yang LP, He Y, Zhang ZF, et al. Upregulation of CEP55 predicts dismal prognosis in patients with liver cancer. Biomed Res Int. 2020;2020:4139320.PubMedPubMedCentral Yang LP, He Y, Zhang ZF, et al. Upregulation of CEP55 predicts dismal prognosis in patients with liver cancer. Biomed Res Int. 2020;2020:4139320.PubMedPubMedCentral
22.
go back to reference Ju LL, Li XF, Shao JG, et al. Upregulation of thyroid hormone receptor interactor 13 is associated with human hepatocellular carcinoma. Oncol Rep. 2018;40(6):3794–802.PubMed Ju LL, Li XF, Shao JG, et al. Upregulation of thyroid hormone receptor interactor 13 is associated with human hepatocellular carcinoma. Oncol Rep. 2018;40(6):3794–802.PubMed
23.
go back to reference Li J, Gao JZ, Du JL, et al. Increased CDC20 expression is associated with development and progression of hepatocellular carcinoma. Int J Oncol. 2014;45(4):1547–55.CrossRefPubMed Li J, Gao JZ, Du JL, et al. Increased CDC20 expression is associated with development and progression of hepatocellular carcinoma. Int J Oncol. 2014;45(4):1547–55.CrossRefPubMed
24.
go back to reference Guan Z, Cheng W, Huang D, et al. High MYBL2 expression and transcription regulatory activity is associated with poor overall survival in patients with hepatocellular carcinoma. Curr Res Translatl Med. 2018;66(1):27–32.CrossRef Guan Z, Cheng W, Huang D, et al. High MYBL2 expression and transcription regulatory activity is associated with poor overall survival in patients with hepatocellular carcinoma. Curr Res Translatl Med. 2018;66(1):27–32.CrossRef
25.
go back to reference Cheng J, Huang Y, Zhang XH, et al. TRIM21 and PHLDA3 negatively regulate the crosstalk between the PI3K/AKT pathway and PPP metabolism. Nat Commun. 2020;11(1):1880.CrossRefPubMedPubMedCentral Cheng J, Huang Y, Zhang XH, et al. TRIM21 and PHLDA3 negatively regulate the crosstalk between the PI3K/AKT pathway and PPP metabolism. Nat Commun. 2020;11(1):1880.CrossRefPubMedPubMedCentral
26.
go back to reference Tekin C, Aberson HL, Bijlsma MF, et al. Early macrophage infiltrates impair pancreatic cancer cell growth by TNF-alpha secretion. Bmc Cancer. 2020;20(1):1–9.CrossRef Tekin C, Aberson HL, Bijlsma MF, et al. Early macrophage infiltrates impair pancreatic cancer cell growth by TNF-alpha secretion. Bmc Cancer. 2020;20(1):1–9.CrossRef
27.
go back to reference Lu HC, Parikh PP, Lorber DL. Phenformin-associated lactic acidosis due to imported phenformin. Diabetes Care. 1996;19(12):1449–50.CrossRefPubMed Lu HC, Parikh PP, Lorber DL. Phenformin-associated lactic acidosis due to imported phenformin. Diabetes Care. 1996;19(12):1449–50.CrossRefPubMed
28.
go back to reference Rubino MEG, Carrillo E, Alcala GR, et al. Phenformin as an anticancer agent: challenges and prospects. Int J Mol Sci. 2019;20(13):3316.CrossRef Rubino MEG, Carrillo E, Alcala GR, et al. Phenformin as an anticancer agent: challenges and prospects. Int J Mol Sci. 2019;20(13):3316.CrossRef
29.
go back to reference Huang LL, Xiao D, Wu TY, et al. Phenformin synergistically sensitizes liver cancer cells to sorafenib by downregulating CRAF/ERK and PI3K/AKT/mTOR pathways. American J Transll Res. 2021;13(7):7508–23. Huang LL, Xiao D, Wu TY, et al. Phenformin synergistically sensitizes liver cancer cells to sorafenib by downregulating CRAF/ERK and PI3K/AKT/mTOR pathways. American J Transll Res. 2021;13(7):7508–23.
30.
go back to reference Li F, Zhang SH, Pang LM. Meta-analysis of efficacy and adverse events of erlotinib-based targeted therapies for advanced/metastatic non-small cell lung cancer. Oncotarget. 2017;8(49):86816–27.CrossRefPubMedPubMedCentral Li F, Zhang SH, Pang LM. Meta-analysis of efficacy and adverse events of erlotinib-based targeted therapies for advanced/metastatic non-small cell lung cancer. Oncotarget. 2017;8(49):86816–27.CrossRefPubMedPubMedCentral
31.
go back to reference Zheng SF, Ni JP, Li Y, et al. 2-Methoxyestradiol synergizes with Erlotinib to suppress hepatocellular carcinoma by disrupting the PLAGL2-EGFR-HIF-1/2 alpha signaling loop. Pharmacol Res. 2021;169:105685. Zheng SF, Ni JP, Li Y, et al. 2-Methoxyestradiol synergizes with Erlotinib to suppress hepatocellular carcinoma by disrupting the PLAGL2-EGFR-HIF-1/2 alpha signaling loop. Pharmacol Res. 2021;169:105685.
32.
go back to reference Zhu AX, Rosmorduc O, Evans TRJ, et al. SEARCH: a phase III, randomized, double-blind, placebo-controlled trial of sorafenib plus erlotinib in patients with advanced hepatocellular carcinoma. J Clin Oncol. 2015;33(6):559–66.CrossRefPubMed Zhu AX, Rosmorduc O, Evans TRJ, et al. SEARCH: a phase III, randomized, double-blind, placebo-controlled trial of sorafenib plus erlotinib in patients with advanced hepatocellular carcinoma. J Clin Oncol. 2015;33(6):559–66.CrossRefPubMed
33.
go back to reference Chen J, Jin RN, Zhao J, et al. Potential molecular, cellular and microenvironmental mechanism of sorafenib resistance in hepatocellular carcinoma. Cancer Lett. 2015;367(1):1–11.CrossRefPubMed Chen J, Jin RN, Zhao J, et al. Potential molecular, cellular and microenvironmental mechanism of sorafenib resistance in hepatocellular carcinoma. Cancer Lett. 2015;367(1):1–11.CrossRefPubMed
34.
go back to reference Li YG, Tang SJ, Shi XH, et al. Metabolic classification suggests the GLUT1/ALDOB/G6PD axis as a therapeutic target in chemotherapy-resistant pancreatic cancer. Cell Rep Med. 2023;4(9):101162.CrossRefPubMedPubMedCentral Li YG, Tang SJ, Shi XH, et al. Metabolic classification suggests the GLUT1/ALDOB/G6PD axis as a therapeutic target in chemotherapy-resistant pancreatic cancer. Cell Rep Med. 2023;4(9):101162.CrossRefPubMedPubMedCentral
35.
go back to reference Junath N, Bharadwaj A, Tyagi S, et al. Prognostic diagnosis for breast cancer patients using probabilistic bayesian classification. Biomed Res Int. 2022;2022:1859222.CrossRefPubMedPubMedCentral Junath N, Bharadwaj A, Tyagi S, et al. Prognostic diagnosis for breast cancer patients using probabilistic bayesian classification. Biomed Res Int. 2022;2022:1859222.CrossRefPubMedPubMedCentral
36.
go back to reference Bo JZ, Li S, Ma PF, et al. Research on Early Warning mechanism and model of liver cancer rehabilitation based on CS-SVM. J Healthcare Eng. 2021;2021:6658776. Bo JZ, Li S, Ma PF, et al. Research on Early Warning mechanism and model of liver cancer rehabilitation based on CS-SVM. J Healthcare Eng. 2021;2021:6658776.
37.
go back to reference Noh MG, Yoon Y, Kim G, et al. Practical prediction model of the clinical response to programmed death-ligand 1 inhibitors in advanced gastric cancer. Exp Mol Med. 2021;53(2):223–34.CrossRefPubMedPubMedCentral Noh MG, Yoon Y, Kim G, et al. Practical prediction model of the clinical response to programmed death-ligand 1 inhibitors in advanced gastric cancer. Exp Mol Med. 2021;53(2):223–34.CrossRefPubMedPubMedCentral
Metadata
Title
G6PD and machine learning algorithms as prognostic and diagnostic indicators of liver hepatocellular carcinoma
Authors
Fei Li
Boshen Wang
Hao Li
Lu Kong
Baoli Zhu
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-024-11887-6

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