An Oxidative Stress-Related Prognostic Signature Predicts Treatment Response and Outcomes for Hepatocellular Carcinoma After Transarterial Chemoembolization

Overview

Journal J Hepatocell Carcinoma

Date 2024 Aug 19

PMID 39156675

Authors

Hui Ma

Ting Yu

Zhong-Chen Li

Lan Zhang

Rong-Xin Chen

Zheng-Gang Ren

Affiliations

Soon will be listed here.

Abstract

Purpose: Oxidative stress plays a critical role in promoting tumor resistance to hypoxia and chemotherapeutic drugs. However, the prognostic role of oxidative stress-related genes (OSRGs) in hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) has not been fully explored.

Methods: We used transcriptome data from the GSE104580 cohort containing patients marked as responders or nonresponders to TACE therapy to identify differentially expressed OSRGs associated with TACE response (TR-OSRGs). We created a TR-OSRG prognostic signature based on TR-OSRGs using least absolute shrinkage and selection operator Cox and stepwise Cox regression analyses in a training cohort of patients with HCC (TCGA-LIHC). We verified this prognostic signature in two external cohorts of patients who received TACE for HCC (GSE14520-TACE and ZS-TACE-37). Finally, we constructed a prognostic nomogram model for predicting survival probability of patients with HCC based on Cox regression analysis.

Results: The TR-OSRG prognostic signature was created and shown to be a robust independent prognostic factor for treatment response and outcomes for HCC after TACE therapy. Risk scores based on this signature correlated with tumor stage and grade. Tumor samples from patients with higher risk scores exhibited more infiltration of immune cells and significantly increased expression of immune checkpoint genes. We also developed a nomogram for patients with HCC based on the TR-OSRG prognostic signature and clinical parameters; this nomogram was a useful quantitative analysis tool for predicting patient survival.

Conclusion: The TR-OSRGs signature exhibited good performance in predicting treatment response and outcomes in patients with HCC treated with TACE.

Citing Articles

Predicting Treatment Response and Prognosis in Patients with Hepatocellular Carcinoma after Interventional Therapy [Letter].

Li H, Shen X, Wu J J Hepatocell Carcinoma. 2024; 11:1741-1742.

PMID: 39314915 PMC: 11417112. DOI: 10.2147/JHC.S494470.

References

Zhu A, Abbas A, Ruiz de Galarreta M, Guan Y, Lu S, Koeppen H . Molecular correlates of clinical response and resistance to atezolizumab in combination with bevacizumab in advanced hepatocellular carcinoma. Nat Med. 2022; 28(8):1599-1611. DOI: 10.1038/s41591-022-01868-2. View

Sung S, Kubo H, Shigemura K, Arnold R, Logani S, Wang R . Oxidative stress induces ADAM9 protein expression in human prostate cancer cells. Cancer Res. 2006; 66(19):9519-26. DOI: 10.1158/0008-5472.CAN-05-4375. View

Wilkerson M, Hayes D . ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking. Bioinformatics. 2010; 26(12):1572-3. PMC: 2881355. DOI: 10.1093/bioinformatics/btq170. View

Srinivas U, Tan B, Vellayappan B, Jeyasekharan A . ROS and the DNA damage response in cancer. Redox Biol. 2019; 25:101084. PMC: 6859528. DOI: 10.1016/j.redox.2018.101084. View

Liu M, Eyries M, Zhang C, Santiago F, Khachigian L . Inducible platelet-derived growth factor D-chain expression by angiotensin II and hydrogen peroxide involves transcriptional regulation by Ets-1 and Sp1. Blood. 2005; 107(6):2322-9. DOI: 10.1182/blood-2005-06-2377. View

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . 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. View

Chou C, Huang Y, Kuo T, Liu J, Sher Y . An Overview of ADAM9: Structure, Activation, and Regulation in Human Diseases. Int J Mol Sci. 2020; 21(20). PMC: 7590139. DOI: 10.3390/ijms21207790. View

Szklarczyk D, Gable A, Nastou K, Lyon D, Kirsch R, Pyysalo S . The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res. 2020; 49(D1):D605-D612. PMC: 7779004. DOI: 10.1093/nar/gkaa1074. View

Ma H, Kang Z, Foo T, Shen Z, Xia B . Disrupted BRCA1-PALB2 interaction induces tumor immunosuppression and T-lymphocyte infiltration in HCC through cGAS-STING pathway. Hepatology. 2022; 77(1):33-47. PMC: 9271123. DOI: 10.1002/hep.32335. View

10.

Llovet J, Kelley R, Villanueva A, Singal A, Pikarsky E, Roayaie S . Hepatocellular carcinoma. Nat Rev Dis Primers. 2021; 7(1):6. DOI: 10.1038/s41572-020-00240-3. View

11.

John T, Liu G, Tsao M . Overview of molecular testing in non-small-cell lung cancer: mutational analysis, gene copy number, protein expression and other biomarkers of EGFR for the prediction of response to tyrosine kinase inhibitors. Oncogene. 2009; 28 Suppl 1:S14-23. DOI: 10.1038/onc.2009.197. View

12.

Yang H, Stern A, Chiu D . G6PD: A hub for metabolic reprogramming and redox signaling in cancer. Biomed J. 2020; 44(3):285-292. PMC: 8358196. DOI: 10.1016/j.bj.2020.08.001. View

13.

Li T, Fan J, Wang B, Traugh N, Chen Q, Liu J . TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells. Cancer Res. 2017; 77(21):e108-e110. PMC: 6042652. DOI: 10.1158/0008-5472.CAN-17-0307. View

14.

Yang H, Wu Y, Yen W, Liu H, Hwang T, Stern A . The Redox Role of G6PD in Cell Growth, Cell Death, and Cancer. Cells. 2019; 8(9). PMC: 6770671. DOI: 10.3390/cells8091055. View

15.

Uchida D, Takaki A, Oyama A, Adachi T, Wada N, Onishi H . Oxidative Stress Management in Chronic Liver Diseases and Hepatocellular Carcinoma. Nutrients. 2020; 12(6). PMC: 7352310. DOI: 10.3390/nu12061576. View

16.

Aboelella N, Brandle C, Kim T, Ding Z, Zhou G . Oxidative Stress in the Tumor Microenvironment and Its Relevance to Cancer Immunotherapy. Cancers (Basel). 2021; 13(5). PMC: 7956301. DOI: 10.3390/cancers13050986. View

17.

Ritchie M, Phipson B, Wu D, Hu Y, Law C, Shi W . limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015; 43(7):e47. PMC: 4402510. DOI: 10.1093/nar/gkv007. View

18.

Tang P, Qu W, Wang T, Liu M, Wu D, Tan L . Identifying a Hypoxia-Related Long Non-Coding RNAs Signature to Improve the Prediction of Prognosis and Immunotherapy Response in Hepatocellular Carcinoma. Front Genet. 2021; 12:785185. PMC: 8669612. DOI: 10.3389/fgene.2021.785185. View

19.

Ma H, Li Z, Chen R, Ren Z . Development of a Combined Oxidative Stress and Endoplasmic Reticulum Stress-Related Prognostic Signature for Hepatocellular Carcinoma. Comb Chem High Throughput Screen. 2023; 27(19):2850-2860. PMC: 11497145. DOI: 10.2174/0113862073257308231026073951. View

20.

Kotsifa E, Vergadis C, Vailas M, Machairas N, Kykalos S, Damaskos C . Transarterial Chemoembolization for Hepatocellular Carcinoma: Why, When, How?. J Pers Med. 2022; 12(3). PMC: 8955120. DOI: 10.3390/jpm12030436. View