An Association Between ATP7B Expression and Human Cancer Prognosis and Immunotherapy: a Pan-cancer Perspective

Overview

Journal BMC Med Genomics

Publisher Biomed Central

Specialty Genetics

Date 2023 Dec 1

PMID 38037104

Authors

Zhanzhan Zhang

Aobo Zhang

Yunpeng Shi

Zijun Zhao

Zongmao Zhao

Affiliations

Soon will be listed here.

Abstract

Background: ATP7B is a copper-transporting protein that contributes to the chemo-resistance of human cancer cells. It remains unclear what the molecular mechanisms behind ATP7B are in cancer, as well as its role in human pan-cancer studies.

Methods: Our study evaluated the differential expression of ATP7B in cancer and paracancerous tissues based on RNA sequencing data from the GTEx and TCGA. Kaplan-Meier and Cox proportional hazards regressions were used to estimate prognostic factors associated with ATP7B.The correlations between the expression of ATP7B and immune cell infiltration, tumor mutation burden, microsatellite instability and immune checkpoint molecules were analyzed. Co-expression networks and mutations in ATP7B were analyzed using the web tools. An analysis of ATP7B expression difference on drug sensitivity on tumor cells was performed using the CTRP, GDSC and CMap database.

Results: ATP7B expression differed significantly between cancerous and paracancerous tissues. The abnormal expression of ATP7B was linked to prognosis in LGG and KIRC. Infiltration of immune cells, tumor mutation burden, microsatellite instability and immunomodulators had all been linked to certain types of cancer. Cancer cells exhibited a correlation between ATP7B expression and drug sensitivity.

Conclusion: ATP7B might be an immunotherapeutic and prognostic biomarker based on its involvement in cancer occurrence and development.

Citing Articles

Pan-cancer analysis reveals copper transporters as promising potential targets.

Li Y, Yu Z Heliyon. 2024; 10(17):e37007.

PMID: 39281483 PMC: 11402228. DOI: 10.1016/j.heliyon.2024.e37007.

References

Modhukur V, Iljasenko T, Metsalu T, Lokk K, Laisk-Podar T, Vilo J . MethSurv: a web tool to perform multivariable survival analysis using DNA methylation data. Epigenomics. 2017; 10(3):277-288. DOI: 10.2217/epi-2017-0118. View

Masetti M, Carriero R, Portale F, Marelli G, Morina N, Pandini M . Lipid-loaded tumor-associated macrophages sustain tumor growth and invasiveness in prostate cancer. J Exp Med. 2021; 219(2). PMC: 8932635. DOI: 10.1084/jem.20210564. View

Sudhahar V, Das A, Horimatsu T, Ash D, Leanhart S, Antipova O . Copper Transporter ATP7A (Copper-Transporting P-Type ATPase/Menkes ATPase) Limits Vascular Inflammation and Aortic Aneurysm Development: Role of MicroRNA-125b. Arterioscler Thromb Vasc Biol. 2019; 39(11):2320-2337. PMC: 6857803. DOI: 10.1161/ATVBAHA.119.313374. View

Guo T, Jiang L, Wang T, Zhang J, Liu Y, Wang X . Screening and identification of prognostic genes associated with eosinophilic features of clear cell renal cell carcinoma. Heliyon. 2023; 9(6):e16479. PMC: 10238738. DOI: 10.1016/j.heliyon.2023.e16479. View

Warde-Farley D, Donaldson S, Comes O, Zuberi K, Badrawi R, Chao P . The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res. 2010; 38(Web Server issue):W214-20. PMC: 2896186. DOI: 10.1093/nar/gkq537. View

Papanicolau-Sengos A, Aldape K . DNA Methylation Profiling: An Emerging Paradigm for Cancer Diagnosis. Annu Rev Pathol. 2021; 17:295-321. DOI: 10.1146/annurev-pathol-042220-022304. View

Wang Y, Lai X, Wang J, Xu Y, Zhang X, Zhu X . A Joint Model Considering Measurement Errors for Optimally Identifying Tumor Mutation Burden Threshold. Front Genet. 2022; 13:915839. PMC: 9386083. DOI: 10.3389/fgene.2022.915839. View

Campagne O, Yeo K, Fangusaro J, Stewart C . Clinical Pharmacokinetics and Pharmacodynamics of Selumetinib. Clin Pharmacokinet. 2020; 60(3):283-303. PMC: 7935771. DOI: 10.1007/s40262-020-00967-y. View

Kanehisa M, Goto S . KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 1999; 28(1):27-30. PMC: 102409. DOI: 10.1093/nar/28.1.27. View

10.

Wang Y, Wang J, Fang W, Xiao X, Wang Q, Zhao J . TMBserval: a statistical explainable learning model reveals weighted tumor mutation burden better categorizing therapeutic benefits. Front Immunol. 2023; 14:1151755. PMC: 10208409. DOI: 10.3389/fimmu.2023.1151755. View

11.

Shanbhag V, Gudekar N, Jasmer K, Papageorgiou C, Singh K, Petris M . Copper metabolism as a unique vulnerability in cancer. Biochim Biophys Acta Mol Cell Res. 2020; 1868(2):118893. PMC: 7779655. DOI: 10.1016/j.bbamcr.2020.118893. View

12.

Chen J, Jiang Y, Shi H, Peng Y, Fan X, Li C . The molecular mechanisms of copper metabolism and its roles in human diseases. Pflugers Arch. 2020; 472(10):1415-1429. DOI: 10.1007/s00424-020-02412-2. View

13.

Hinshaw D, Shevde L . The Tumor Microenvironment Innately Modulates Cancer Progression. Cancer Res. 2019; 79(18):4557-4566. PMC: 6744958. DOI: 10.1158/0008-5472.CAN-18-3962. View

14.

Moinuddin F, Hirano H, Shinsato Y, Higa N, Arita K, Furukawa T . ATP7B expression in human glioblastoma is related to temozolomide resistance. Oncol Lett. 2017; 14(6):7777-7782. PMC: 5727628. DOI: 10.3892/ol.2017.7249. View

15.

Fouani L, Menezes S, Paulson M, Richardson D, Kovacevic Z . Metals and metastasis: Exploiting the role of metals in cancer metastasis to develop novel anti-metastatic agents. Pharmacol Res. 2016; 115:275-287. DOI: 10.1016/j.phrs.2016.12.001. View

16.

Anh N, Thuong P, Sim N, Thao T, Lan Anh L, Canh T . Maternal vascular endothelial growth factor receptor and interleukin levels in pregnant women with twin-twin transfusion syndrome. Int J Med Sci. 2021; 18(14):3206-3213. PMC: 8364448. DOI: 10.7150/ijms.61014. View

17.

Boutilier A, Elsawa S . Macrophage Polarization States in the Tumor Microenvironment. Int J Mol Sci. 2021; 22(13). PMC: 8268869. DOI: 10.3390/ijms22136995. View

18.

Anuraga G, Wang W, Phan N, An Ton N, Ta H, Prayugo F . Potential Prognostic Biomarkers of NIMA (Never in Mitosis, Gene A)-Related Kinase (NEK) Family Members in Breast Cancer. J Pers Med. 2021; 11(11). PMC: 8625415. DOI: 10.3390/jpm11111089. View

19.

Li Y, Yin J, Liu Z, Li X . Copper efflux transporters ATP7A and ATP7B: Novel biomarkers for platinum drug resistance and targets for therapy. IUBMB Life. 2018; 70(3):183-191. DOI: 10.1002/iub.1722. View

20.

Yu Z, Zhou R, Zhao Y, Pan Y, Liang H, Zhang J . Blockage of SLC31A1-dependent copper absorption increases pancreatic cancer cell autophagy to resist cell death. Cell Prolif. 2019; 52(2):e12568. PMC: 6496122. DOI: 10.1111/cpr.12568. View