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Original Research

Open Access

Estrogen receptor 1 and Aurora kinase A as potential diagnostic biomarkers for cervical cancer

  • Huaqiu Chen1,2,†
  • Xingyou Chen2,†
  • Xi Yuan2
  • Yuanyuan Zhang1,*,
  • Guangming Wang1,*,

1School of clinical medicine, Dali University, 671000 Dali, Yunnan, China

2Xichang people’s Hospital, 615000 Xichang, Sichuan, China

DOI: 10.22514/ejgo.2022.025 Vol.43,Issue 5,October 2022 pp.32-41

Submitted: 18 May 2022 Accepted: 17 June 2022

Published: 15 October 2022

*Corresponding Author(s): Yuanyuan Zhang E-mail: zhyy@dali.edu.cn
*Corresponding Author(s): Guangming Wang E-mail: wgm1991@dali.edu.cn

† These authors contributed equally.

Abstract

Cervical cancer (CC) is the fourth most common cause of death among women globally. Nearly 90% of CC mortality occurs in low- and middle-income countries. Hence there is an urgent need for identification of new biomarkers for the early diagnosis and treatment of CC. Current research aims to investigate the effect and mechanism of estrogen receptor 1 and aurora kinase A as potential diagnostic biomarkers for cervical cancer. Gene microarray datasets GSE8703 and GSE9750 were acquired from the Gene Set Omnibus and evaluated using GEO2R to identify the differentially expressed genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially expressed genes were performed using the clusterProfiler R package. A protein-protein interaction (PPI) network was constructed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and visualized using Cytoscape; hub genes were screened using the cytoHubba plug-in. Receiver operating characteristic curve and survival analysis was performed for candidate genes in the Gene Expression Profiling Interactive Analysis Database. The University of California, Santa Cruz, (UCSC)-XENA platform was used to analyze the pan-cancer biomarker expression. The relative expression of biomarkers in normal and cervical cancer tissues was determined using the Human Protein Atlas Database. Estrogen receptor 1 (ESR1) and Aurora kinase A (AURKA) were identified as potential biomarkers for cervical cancer. ESR1 was actively expressed in normal cervical tissues but limited in cervical cancer tissues. AURKA was least expressed in normal tissues and highly expressed in cervical cancer tissues. The results were confirmed by immunohistochemistry. The biomarkers identified herein can enable early diagnosis and serve as the therapeutic targets for cervical cancer.


Keywords

Cervical cancer; Differentially expressed genes; Biomarker; Protein-protein interaction; Hub gene


Cite and Share

Huaqiu Chen,Xingyou Chen,Xi Yuan,Yuanyuan Zhang,Guangming Wang. Estrogen receptor 1 and Aurora kinase A as potential diagnostic biomarkers for cervical cancer. European Journal of Gynaecological Oncology. 2022. 43(5);32-41.

References

[1] Arbyn M, Weiderpass E, Bruni L, de Sanjosé S, Saraiya M, Ferlay J, et al. Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. The Lancet Global Health. 2020; 8: e191–e203.

[2] Zhang X, Zeng Q, Cai W, Ruan W. Trends of cervical cancer at global, regional, and national level: data from the Global Burden of Disease study 2019. BMC Public Health. 2021; 21: 894.

[3] Wentzensen N, Clarke MA. Cervical cancer screening—past, present, and future. Cancer Epidemiology, Biomarkers & Prevention. 2021; 30: 432–434.

[4] Rodin D, Burger EA, Atun R, Barton M, Gospodarowicz M, Grover S, et al. Scale-up of radiotherapy for cervical cancer in the era of human papillomavirus vaccination in low-income and middle-income countries: a model-based analysis of need and economic impact. The Lancet Oncology. 2019; 20: 915–923.

[5] Vu M, Yu J, Awolude OA, Chuang L. Cervical cancer worldwide. Current Problems in Cancer. 2018; 42: 457–465.

[6] Bao HL, Zhao ZP, Zhang M, Wang LM, Cong S, Fang LW, et al. The impact of five-year Chinese rural area cervical cancer screening program on screening rate. Zhonghua Yu Fang Yi Xue Za Zhi. 2018; 52: 260–264.(In Chinese)

[7] Luo XM, Song L, Wu JL, Liu Y, Di JL, Song B, et al. Analysis of the reported data of national rural cervical cancer screening project from 2012 to 2013, China. Zhonghua Yu Fang Yi Xue Za Zhi. 2016; 50: 346–350.(In Chinese)

[8] Teng P, Hao M. A population-based study of age-related associations between vaginal pH and the development of cervical intraepithelial neoplasia. Cancer Medicine. 2020; 9: 1890–1902.

[9] Sankaranarayanan R, Prabhu PR, Pawlita M, Gheit T, Bhatla N, Muwonge R, et al. Immunogenicity and HPV infection after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre prospective cohort study. The Lancet Oncology. 2016; 17: 67–77.

[10] Howley PM, Livingston DM. Small DNA tumor viruses: large contributors to biomedical sciences. Virology. 2009; 384: 256–259.

[11] PC Yee G, de Souza P, M Khachigian L. Current and potential treatments for cervical cancer. Current Cancer Drug Targets. 2013; 13: 205–220.

[12] Thomas A, Redon CE, Sciuto L, Padiernos E, Ji J, Lee MJ, et al. Phase I study of ATR inhibitor M6620 in combination with topotecan in patients with advanced solid tumors. Journal of Clinical Oncology. 2018; 36: 1594–1602.

[13] Housman G, Byler S, Heerboth S, Lapinska K, Longacre M, Snyder N, et al. Drug resistance in cancer: an overview. Cancers. 2014; 6: 1769–1792.

[14] Steeg PS. Targeting metastasis. Nature Reviews Cancer. 2016; 16: 201–218.

[15] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2018; 68: 394–424.

[16] Wang W, Li L, Wu M, Ma S, Tan X, Zhong S, et al. Laparoscopic vs. abdominal radical hysterectomy for locally advanced cervical cancer. Frontiers in Oncology. 2019; 9: 1331.

[17] Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, et al. NCBI GEO: archive for functional genomics data sets—update. Nucleic Acids Research. 2013; 41: D991–D995.

[18] Vivian J, Rao AA, Nothaft FA, Ketchum C, Armstrong J, Novak A, et al. Toil enables reproducible, open source, big biomedical data analyses. Nature Biotechnology. 2017; 35: 314–316.

[19] Digre A, Lindskog C. The human protein atlas—spatial localization of the human proteome in health and disease. Protein Science. 2021; 30: 218–233.

[20] Gautschi O, Heighway J, Mack PC, Purnell PR, Lara PN, Gandara DR. Aurora kinases as anticancer drug targets. Clinical Cancer Research. 2008; 14: 1639–1648.

[21] Keen N, Taylor S. Aurora-kinase inhibitors as anticancer agents. Nature Reviews Cancer. 2004; 4: 927–936.

[22] Sen S, Zhou H, White RA. A putative serine/threonine kinase encoding gene BTAK on chromosome 20q13 is amplified and overexpressed in human breast cancer cell lines. Oncogene. 1997; 14: 2195–2200.

[23] Xie Y, Zhu S, Zhong M, Yang M, Sun X, Liu J, et al. Inhibition of Aurora kinase A induces necroptosis in pancreatic carcinoma. Gastroenterology. 2017; 153: 1429–1443.e5.

[24] Marumoto T, Zhang D, Saya H. Aurora-A—a guardian of poles. Nature Reviews Cancer. 2005; 5: 42–50.

[25] Sehdev V, Katsha A, Arras J, Peng D, Soutto M, Ecsedy J, et al. HDM2 regulation by AURKA promotes cell survival in gastric cancer. Clinical Cancer Research. 2014; 20: 76–86.

[26] Dar AA, Belkhiri A, Ecsedy J, Zaika A, El-Rifai W. Aurora kinase A inhibition leads to p73-dependent apoptosis in p53-deficient cancer cells. Cancer Research. 2008; 68: 8998–9004.

[27] Shao S, Wang C, Wang S, Zhang H, Zhang Y. Hsa_circ_0075341 is up-regulated and exerts oncogenic properties by sponging miR-149-5p in cervical cancer. Biomedicine & Pharmacotherapy. 2020; 121: 109582.

[28] Dobson T, Chen J, Krushel LA. Dysregulating IRES-dependent trans-lation contributes to overexpression of oncogenic Aurora A kinase. Molecular Cancer Research. 2013; 11: 887–900.

[29] Zhong Y, Yang J, Xu WW, Wang Y, Zheng C, Li B, et al. KCTD12 promotes tumorigenesis by facilitating CDC25B/CDK1/Aurora A- dependent G2/M transition. Oncogene. 2017; 36: 6177–6189.

[30] Yang SB, Zhou XB, Zhu HX, Quan LP, Bai JF, He J, et al. Amplification and overexpression of Aurora-A in esophageal squamous cell carcinoma. Oncology Reports. 2007; 17: 1083–1088.

[31] Mehra R, Serebriiskii IG, Burtness B, Astsaturov I, Golemis EA. Aurora kinases in head and neck cancer. The Lancet Oncology. 2013; 14: e425–e435.

[32] Li M, Ren ZG. The function of Aurora A and its role in the development of liver cancer. Zhonghua Gan Zang Bing Za Zhi. 2017; 25: 477–480. (In Chinese)

[33] Bosch FX, Broker TR, Forman D, Moscicki A, Gillison ML, Doorbar J, et al. Comprehensive control of human papillomavirus infections and related diseases. Vaccine. 2013; 31: H1–H31.

[34] Ma Y, Yang J, Wang R, Zhang Z, Qi X, Liu C, et al. Aurora-A affects radiosenstivity in cervical squamous cell carcinoma and predicts poor prognosis. Oncotarget. 2017; 8: 31509–31520.

[35] Katsha A, Arras J, Soutto M, Belkhiri A, El-Rifai W. AURKA regulates JAK2-STAT3 activity in human gastric and esophageal cancers. Molecular Oncology. 2014; 8: 1419–1428.

[36] Landen CN, Lin YG, Immaneni A, Deavers MT, Merritt WM, Spannuth WA, et al. Overexpression of the centrosomal protein Aurora-A kinase is associated with poor prognosis in epithelial ovarian cancer patients. Clinical Cancer Research. 2007; 13: 4098–4104.

[37] Sankaran S, Crone DE, Palazzo RE, Parvin JD. Aurora-A kinase regulates breast cancer—associated gene 1 inhibition of centrosome-dependent microtubule nucleation. Cancer Research. 2007; 67: 11186–11194.

[38] Liu Y, Liao S, Bennett S, Tang H, Song D, Wood D, et al. STAT3 and its targeting inhibitors in osteosarcoma. Cell Proliferation. 2021; 54: e12974.

[39] Herynk MH, Fuqua SAW. Estrogen receptors in resistance to hormone therapy. In Yu DH, Hung M-C (eds.). Breast Cancer Chemosensitivity (pp.130–143). 1st edn. Springer: New York. 2007.

[40] Chen Y, Gu Y, Gu Y, Wu J. Long noncoding RNA LINC00899/miR-944/ESR1 axis regulates cervical cancer cell proliferation, migration, and invasion. Journal of Interferon & Cytokine Research. 2021; 41: 220–233.

[41] Hong M, Wang J, Su C, Li M, Hsu Y, Chu T. Expression of estrogen and progesterone receptor in tumor stroma predicts favorable prognosis of cervical squamous cell carcinoma. International Journal of Gynecologic Cancer. 2017; 27: 1247–1255.

[42] Zhai Y, Bommer GT, Feng Y, Wiese AB, Fearon ER, Cho KR. Loss of estrogen receptor 1 enhances cervical cancer invasion. The American Journal of Pathology. 2010; 177: 884–895.

[43] Huang B, Warner M, Gustafsson J. Estrogen receptors in breast carcino-genesis and endocrine therapy. Molecular and Cellular Endocrinology. 2015; 418: 240–244.

[44] Gong G, Lin T, Yuan Y. Integrated analysis of gene expression and DNA methylation profiles in ovarian cancer. Journal of Ovarian Research. 2020; 13: 30.

[45] Jiao X, Zhang S, Jiao J, Zhang T, Qu W, Muloye GM, et al. Promoter methylation of SEPT9 as a potential biomarker for early detection of cervical cancer and its overexpression predicts radioresistance. Clinical Epigenetics. 2019; 11: 120.

[46] Zhao J, Cao H, Zhang W, Fan Y, Shi S, Wang R. SOX14 hypermethylation as a tumour biomarker in cervical cancer. BMC Cancer. 2021; 21: 675.

[47] Tu S, Zhang H, Yang X, Wen W, Song K, Yu X, et al. Screening of cervical cancer-related hub genes based on comprehensive bioinformatics analysis. Cancer Biomarkers. 2021; 32: 303–315.

[48] Ma X, Liu J, Wang H, Jiang Y, Wan Y, Xia Y, et al. Identification of crucial aberrantly methylated and differentially expressed genes related to cervical cancer using an integrated bioinformatics analysis. Bioscience Reports. 2020; 40: BSR20194365.


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