Identification of GINS1 As a Therapeutic Target in the Cancer Patients Infected with COVID-19: a Bioinformatics and System Biology Approach

Overview

Journal Hereditas

Specialty Genetics

Date 2022 Dec 1

PMID 36451247

Authors

Changpeng Hu

Yue Dai

Huyue Zhou

Jing Zhang

Dandan Xie

Rufu Xu

Mengmeng Yang

Rong Zhang

Affiliations

Soon will be listed here.

Abstract

Background: Coronavirus disease 2019 (COVID-19) caused a series of biological changes in cancer patients which have rendered the original treatment ineffective and increased the difficulty of clinical treatment. However, the clinical treatment for cancer patients infected with COVID-19 is currently unavailable. Since bioinformatics is an effective method to understand undiscovered biological functions, pharmacological targets, and therapeutic mechanisms. The aim of this study was to investigate the influence of COVID-19 infection in cancer patients and to search the potential treatments.

Methods: Firstly, we obtained the COVID-19-associated genes from seven databases and analyzed the cancer pathogenic genes from Gene Expression Omnibus (GEO) databases, respectively. The Cancer/COVID-19-associated genes were shown by Venn analyses. Moreover, we demonstrated the signaling pathways and biological functions of pathogenic genes in Cancer/COVID-19.

Results: We identified that Go-Ichi-Ni-San complex subunit 1 (GINS1) is the potential therapeutic target in Cancer/COVID-19 by GEPIA. The high expression of GINS1 was not only promoting the development of cancers but also affecting their prognosis. Furthermore, eight potential compounds of Cancer/COVID-19 were identified from CMap and molecular docking analysis.

Conclusion: We revealed the GINS1 is a potential therapeutic target in cancer patients infected with COVID-19 for the first time, as COVID-19 will be a severe and prolonged pandemic. However, the findings have not been verified actually cancer patients infected with COVID-19, and further studies are needed to demonstrate the functions of GINS1 and the clinical treatment of the compounds.

References

Muus C, Luecken M, Eraslan G, Sikkema L, Waghray A, Heimberg G . Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics. Nat Med. 2021; 27(3):546-559. PMC: 9469728. DOI: 10.1038/s41591-020-01227-z. View

Wen J, Han X, Wei B, Zhang S, Wei H . [Expression of PSF1 in colon cancer tissues and its effect on the proliferation of colon cancer cells]. Zhonghua Wei Chang Wai Ke Za Zhi. 2013; 16(1):70-4. View

Nagahama Y, Ueno M, Miyamoto S, Morii E, Minami T, Mochizuki N . PSF1, a DNA replication factor expressed widely in stem and progenitor cells, drives tumorigenic and metastatic properties. Cancer Res. 2010; 70(3):1215-24. DOI: 10.1158/0008-5472.CAN-09-3662. View

Wu J, Leung K, Lam T, Ni M, Wong C, Peiris J . Nowcasting epidemics of novel pathogens: lessons from COVID-19. Nat Med. 2021; 27(3):388-395. DOI: 10.1038/s41591-021-01278-w. View

Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S . SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020; 181(2):271-280.e8. PMC: 7102627. DOI: 10.1016/j.cell.2020.02.052. View

Boos D, Yekezare M, Diffley J . Identification of a heteromeric complex that promotes DNA replication origin firing in human cells. Science. 2013; 340(6135):981-4. DOI: 10.1126/science.1237448. View

Xia Q, Xun Y, Lu J, Lu Y, Yang Y, Zhou P . Network pharmacology and molecular docking analyses on Lianhua Qingwen capsule indicate Akt1 is a potential target to treat and prevent COVID-19. Cell Prolif. 2020; 53(12):e12949. PMC: 7705900. DOI: 10.1111/cpr.12949. View

Dai M, Liu D, Liu M, Zhou F, Li G, Chen Z . Patients with Cancer Appear More Vulnerable to SARS-CoV-2: A Multicenter Study during the COVID-19 Outbreak. Cancer Discov. 2020; 10(6):783-791. PMC: 7309152. DOI: 10.1158/2159-8290.CD-20-0422. View

Qin X, Huang C, Wu K, Li Y, Liang X, Su M . Anti-coronavirus disease 2019 (COVID-19) targets and mechanisms of puerarin. J Cell Mol Med. 2020; 25(2):677-685. PMC: 7753316. DOI: 10.1111/jcmm.16117. View

10.

Yoshida M, Ishioka Y, Ozawa T, Okuyama H, Iguchi M, Ota T . Soluble HLA-associated peptide from PSF1 has a cancer vaccine potency. Sci Rep. 2017; 7(1):11137. PMC: 5593935. DOI: 10.1038/s41598-017-11605-2. View

11.

Blees A, Januliene D, Hofmann T, Koller N, Schmidt C, Trowitzsch S . Structure of the human MHC-I peptide-loading complex. Nature. 2017; 551(7681):525-528. DOI: 10.1038/nature24627. View

12.

Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z . GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017; 45(W1):W98-W102. PMC: 5570223. DOI: 10.1093/nar/gkx247. View

13.

Li F, Li Y, Liu M, Fang L, Dean N, Wong G . Household transmission of SARS-CoV-2 and risk factors for susceptibility and infectivity in Wuhan: a retrospective observational study. Lancet Infect Dis. 2021; 21(5):617-628. PMC: 7833912. DOI: 10.1016/S1473-3099(20)30981-6. View

14.

Zhang J, Wu Q, Wang Z, Zhang Y, Zhang G, Fu J . Knockdown of PSF1 expression inhibits cell proliferation in lung cancer cells in vitro. Tumour Biol. 2014; 36(3):2163-8. DOI: 10.1007/s13277-014-2826-8. View

15.

Fitzmaurice C, Allen C, Barber R, Barregard L, Bhutta Z, Brenner H . Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol. 2016; 3(4):524-548. PMC: 6103527. DOI: 10.1001/jamaoncol.2016.5688. View

16.

Lee L, Cazier J, Angelis V, Arnold R, Bisht V, Campton N . COVID-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: a prospective cohort study. Lancet. 2020; 395(10241):1919-1926. PMC: 7255715. DOI: 10.1016/S0140-6736(20)31173-9. View

17.

Vatansev H, Kadiyoran C, Cumhur Cure M, Cure E . COVID-19 infection can cause chemotherapy resistance development in patients with breast cancer and tamoxifen may cause susceptibility to COVID-19 infection. Med Hypotheses. 2020; 143:110091. PMC: 7347308. DOI: 10.1016/j.mehy.2020.110091. View

18.

Lievre A, Turpin A, Ray-Coquard I, Le Malicot K, Thariat J, Ahle G . Risk factors for Coronavirus Disease 2019 (COVID-19) severity and mortality among solid cancer patients and impact of the disease on anticancer treatment: A French nationwide cohort study (GCO-002 CACOVID-19). Eur J Cancer. 2020; 141:62-81. PMC: 7543792. DOI: 10.1016/j.ejca.2020.09.035. View

19.

Lamb J . The Connectivity Map: a new tool for biomedical research. Nat Rev Cancer. 2006; 7(1):54-60. DOI: 10.1038/nrc2044. View

20.

Schultze J, Aschenbrenner A . COVID-19 and the human innate immune system. Cell. 2021; 184(7):1671-1692. PMC: 7885626. DOI: 10.1016/j.cell.2021.02.029. View