Integrative Systems Biology Approaches to Identify Potential Biomarkers and Pathways of Cervical Cancer

Overview

Journal J Pers Med

Date 2021 May 5

PMID 33946372

Citations 8

Authors

Arafat Rahman Oany

Mamun Mia

Tahmina Pervin

Salem Ali Alyami

Mohammad Ali Moni

Affiliations

Soon will be listed here.

Abstract

Nowadays, cervical cancer (CC) is treated as the leading cancer among women throughout the world. Despite effective vaccination and improved surgery and treatment, CC retains its fatality rate of about half of the infected population globally. The major screening biomarkers and therapeutic target identification have now become a global concern. In the present study, we have employed systems biology approaches to retrieve the potential biomarkers and pathways from transcriptomic profiling. Initially, we have identified 76 of each up-regulated and down-regulated gene from a total of 4643 differentially expressed genes. The up-regulatory genes mainly concentrate on immune-inflammatory responses, and the down-regulatory genes are on receptor binding and gamma-glutamyltransferase. The involved pathways associated with these genes were also assessed through pathway enrichment, and we mainly focused on different cancer pathways, immunoresponse, and cell cycle pathways. After the subsequent enrichment of these genes, we have identified 12 hub genes, which play a crucial role in CC and are verified by expression profile analysis. From our study, we have found that genes LILRB2 and CYBB play crucial roles in CC, as reported here for the first time. Furthermore, the survivability of the hub genes was also assessed, and among them, finally, CXCR4 has been identified as one of the most potential differentially expressed genes that might play a vital role in the survival of CC patients. Thus, CXCR4 could be used as a prognostic and/or diagnostic biomarker and a drug target for CC.

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References

Zhang J, Lu W, Ye F, Chen H, Zhou C, Xie X . Study on CXCR4/SDF-1alpha axis in lymph node metastasis of cervical squamous cell carcinoma. Int J Gynecol Cancer. 2007; 17(2):478-83. DOI: 10.1111/j.1525-1438.2007.00786.x. View

Dehn D, Torkko K, Shroyer K . Human papillomavirus testing and molecular markers of cervical dysplasia and carcinoma. Cancer. 2007; 111(1):1-14. DOI: 10.1002/cncr.22425. View

Smith M, Luker K, Garbow J, Prior J, Jackson E, Piwnica-Worms D . CXCR4 regulates growth of both primary and metastatic breast cancer. Cancer Res. 2004; 64(23):8604-12. DOI: 10.1158/0008-5472.CAN-04-1844. View

Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J . STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 2014; 43(Database issue):D447-52. PMC: 4383874. DOI: 10.1093/nar/gku1003. View

Domingos-Pereira S, Decrausaz L, Derre L, Bobst M, Romero P, Schiller J . Intravaginal TLR agonists increase local vaccine-specific CD8 T cells and human papillomavirus-associated genital-tumor regression in mice. Mucosal Immunol. 2012; 6(2):393-404. PMC: 3573262. DOI: 10.1038/mi.2012.83. View

Sekula M, Miekus K, Majka M . Downregulation of the CXCR4 receptor inhibits cervical carcinoma metastatic behavior in vitro and in vivo. Int J Oncol. 2014; 44(6):1853-60. PMC: 4063539. DOI: 10.3892/ijo.2014.2383. View

Chen A, Qin Y, Tang W, Tao J, Song H, Zuo M . MiR-34a and miR-206 act as novel prognostic and therapy biomarkers in cervical cancer. Cancer Cell Int. 2017; 17:63. PMC: 5466768. DOI: 10.1186/s12935-017-0431-9. View

Jiao X, Sherman B, Huang D, Stephens R, Baseler M, Lane H . DAVID-WS: a stateful web service to facilitate gene/protein list analysis. Bioinformatics. 2012; 28(13):1805-6. PMC: 3381967. DOI: 10.1093/bioinformatics/bts251. View

Leite G, Scicluna B, van der Poll T, Salomao R . Genetic signature related to heme-hemoglobin metabolism pathway in sepsis secondary to pneumonia. NPJ Syst Biol Appl. 2019; 5:26. PMC: 6672010. DOI: 10.1038/s41540-019-0105-4. View

10.

Yadav S, Prasad S, Das M, Kumari S, Pandey L, Singh S . Epigenetic silencing of CXCR4 promotes loss of cell adhesion in cervical cancer. Biomed Res Int. 2014; 2014:581403. PMC: 4119908. DOI: 10.1155/2014/581403. View

11.

Peng Y, Wu D, Li F, Zhang P, Feng Y, He A . Identification of key biomarkers associated with cell adhesion in multiple myeloma by integrated bioinformatics analysis. Cancer Cell Int. 2020; 20:262. PMC: 7309988. DOI: 10.1186/s12935-020-01355-z. View

12.

Pan X, Lu Y, Huang J, Long Y, Yao D . Prognostic genes in the tumor microenvironment in cervical squamous cell carcinoma. Aging (Albany NY). 2019; 11(22):10154-10166. PMC: 6914434. DOI: 10.18632/aging.102429. View

13.

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

14.

Chin C, Chen S, Wu H, Ho C, Ko M, Lin C . cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol. 2014; 8 Suppl 4:S11. PMC: 4290687. DOI: 10.1186/1752-0509-8-S4-S11. View

15.

McIntyre J, Wu J, Craighead P, Phan T, Kobel M, Lees-Miller S . PIK3CA mutational status and overall survival in patients with cervical cancer treated with radical chemoradiotherapy. Gynecol Oncol. 2012; 128(3):409-14. DOI: 10.1016/j.ygyno.2012.12.019. View

16.

Oany A, Mia M, Pervin T, Junaid M, Hosen S, Moni M . Design of novel viral attachment inhibitors of the spike glycoprotein (S) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) through virtual screening and dynamics. Int J Antimicrob Agents. 2020; 56(6):106177. PMC: 7518233. DOI: 10.1016/j.ijantimicag.2020.106177. View

17.

Kim S, Chun M, Ryu H, Chang S, Kong T, Lee E . Salvage radiotherapy with or without concurrent chemotherapy for pelvic recurrence after hysterectomy alone for early-stage uterine cervical cancer. Strahlenther Onkol. 2017; 193(7):534-542. DOI: 10.1007/s00066-017-1122-0. View

18.

Waggoner S . Cervical cancer. Lancet. 2003; 361(9376):2217-25. DOI: 10.1016/S0140-6736(03)13778-6. View

19.

Oany A, Pervin T, Mia M, Hossain M, Shahnaij M, Mahmud S . Vaccinomics Approach for Designing Potential Peptide Vaccine by Targeting spp. Serine Protease Autotransporter Subfamily Protein SigA. J Immunol Res. 2017; 2017:6412353. PMC: 5610819. DOI: 10.1155/2017/6412353. View

20.

Pawitan Y, Michiels S, Koscielny S, Gusnanto A, Ploner A . False discovery rate, sensitivity and sample size for microarray studies. Bioinformatics. 2005; 21(13):3017-24. DOI: 10.1093/bioinformatics/bti448. View