SOX14 Hypermethylation As a Tumour Biomarker in Cervical Cancer

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2021 Jun 8

PMID 34098886

Citations 5

Authors

Jing Zhao

Huiling Cao

Wenfan Zhang

Yongjuan Fan

Shujuan Shi

Rong Wang

Affiliations

Soon will be listed here.

Abstract

Background: The association between SOX14 and cancer has been reported. The aim of this study was to identify and validate the potential value of SOX14 methylation in the early detection of cervical cancer.

Methods: First, we extracted the data for SOX14 methylation and expression within cervical cancer from The Cancer Genome Atlas (TCGA) database and analysed them via UALCAN, Wanderer, MEXPRESS and LinkedOmics. Subsequently, according to the bioinformatics findings, primers and probes were designed for the most significantly differentiated methylation CpG site and synthesized for methylation-specific PCR (MSP) and quantitative methylation-specific PCR (QMSP) to verify SOX14 methylation in both cervical tissuses and liquid-based cell samples. Eventually, the clinical diagnostic efficacy of SOX14 methylation in the normal, cervical intraepithelial neoplasia, and cancer groups was analysed by ROC.

Results: Pooled analysis demonstrated that SOX14 methylation levels were significantly increased in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) compared to normal tissues (P < 0.001). Both the verification and validation cohorts indicated that the methylation level and the positive rate of SOX14 gradually increased with increasing severity from normal to cancer samples (P < 0.01). When the cut-off value was set as 128.45, the sensitivity and specificity of SOX14 hypermethylation in the diagnosis of cervical cancer were 94.12 and 86.46%, respectively. When taken as a screening biomarker (>CINII), the sensitivity was 74.42% and the specificity was 81.48%, with a cut-off value of 10.37.

Conclusion: SOX14 hypermethylation is associated with cervical cancer and has the potential to be a molecular biomarker for the screening and early diagnosis of cervical cancer.

Citing Articles

Identification of a novel hypermethylation marker, ZSCAN18, and construction of a diagnostic model in cervical cancer.

Yang J, Chen S, Liu Y, Wang P, Zhao J, Yi J Clin Transl Oncol. 2025; .

PMID: 39969762 DOI: 10.1007/s12094-025-03864-7.

Association between SOX gene family expression, DNA methylation, and miRNA regulation in lung adenocarcinoma progression.

Wang H, Hu Y, Lu H, Wu Z, Zhang Y Discov Oncol. 2025; 16(1):188.

PMID: 39954219 PMC: 11829875. DOI: 10.1007/s12672-025-01892-x.

Expression and hypermethylation of JAM and EPB41L3 in cervical squamous cell carcinoma: Clinical significance and applications.

Gu Y, Chu C, Yuan B, Wang J, Pan S Histol Histopathol. 2024; 39(8):1043-1051.

PMID: 38213260 DOI: 10.14670/HH-18-697.

Clinical Significance of SOX10 Expression in Human Pathology.

Bahmad H, Thiravialingam A, Sriganeshan K, Gonzalez J, Alvarez V, Ocejo S Curr Issues Mol Biol. 2023; 45(12):10131-10158.

PMID: 38132479 PMC: 10742133. DOI: 10.3390/cimb45120633.

Cervical Cancer Prophylaxis-State-of-the-Art and Perspectives.

Poniewierza P, Panek G Healthcare (Basel). 2022; 10(7).

PMID: 35885852 PMC: 9319342. DOI: 10.3390/healthcare10071325.

References

Locke W, Guanzon D, Ma C, Liew Y, Duesing K, Fung K . DNA Methylation Cancer Biomarkers: Translation to the Clinic. Front Genet. 2019; 10:1150. PMC: 6870840. DOI: 10.3389/fgene.2019.01150. View

Tay T, Lim K, Hilmy M, Thike A, Goh S, Song L . Comparison of the sensitivity and specificity of p16/Ki-67 dual staining and HPV DNA testing of abnormal cervical cytology in the detection of histology proven cervical intraepithelial neoplasia grade 2 and above (CIN 2+). Malays J Pathol. 2017; 39(3):257-265. View

Lei X, Liu Y, Wang J, Cai Q, Yan M, He H . SOX1 promotes differentiation of nasopharyngeal carcinoma cells by activating retinoid metabolic pathway. Cell Death Dis. 2020; 11(5):331. PMC: 7206110. DOI: 10.1038/s41419-020-2513-1. View

Li N, Li S . Epigenetic inactivation of SOX1 promotes cell migration in lung cancer. Tumour Biol. 2015; 36(6):4603-10. DOI: 10.1007/s13277-015-3107-x. View

Rebolj M, Rimmer J, Denton K, Tidy J, Mathews C, Ellis K . Primary cervical screening with high risk human papillomavirus testing: observational study. BMJ. 2019; 364:l240. PMC: 6364146. DOI: 10.1136/bmj.l240. View

Bray F, Lortet-Tieulent J, Znaor A, Brotons M, Poljak M, Arbyn M . Patterns and trends in human papillomavirus-related diseases in Central and Eastern Europe and Central Asia. Vaccine. 2013; 31 Suppl 7:H32-45. DOI: 10.1016/j.vaccine.2013.02.071. View

Li J, Shen J, Wang K, Hornicek F, Duan Z . The Roles of Sox Family Genes in Sarcoma. Curr Drug Targets. 2016; 17(15):1761-1772. DOI: 10.2174/1389450117666160502145311. View

Wang B, He M, Chao A, Engelgau M, Saraiya M, Wang L . Cervical Cancer Screening Among Adult Women in China, 2010. Oncologist. 2015; 20(6):627-34. PMC: 4571778. DOI: 10.1634/theoncologist.2014-0303. View

Mayrand M, Duarte-Franco E, Rodrigues I, Walter S, Hanley J, Ferenczy A . Human papillomavirus DNA versus Papanicolaou screening tests for cervical cancer. N Engl J Med. 2007; 357(16):1579-88. DOI: 10.1056/NEJMoa071430. View

10.

Lees B, Erickson B, Huh W . Cervical cancer screening: evidence behind the guidelines. Am J Obstet Gynecol. 2015; 214(4):438-443. DOI: 10.1016/j.ajog.2015.10.147. View

11.

Garcia I, Aldaregia J, Marjanovic Vicentic J, Aldaz P, Moreno-Cugnon L, Torres-Bayona S . Oncogenic activity of SOX1 in glioblastoma. Sci Rep. 2017; 7:46575. PMC: 5397861. DOI: 10.1038/srep46575. View

12.

Man C, Kan Fung T, Wan H, Cher C, Fan A, Ng N . Suppression of SOX7 by DNA methylation and its tumor suppressor function in acute myeloid leukemia. Blood. 2015; 125(25):3928-36. DOI: 10.1182/blood-2014-06-580993. View

13.

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

14.

Wu N, Zhang X, Chu T, Zhu S, Deng Y, Zhou Y . High methylation of in cervical adenocarcinoma affects radiosensitivity and prognosis. Ann Transl Med. 2019; 7(14):328. PMC: 6694254. DOI: 10.21037/atm.2019.06.15. View

15.

Hu J, Li K, Li Z, Gao C, Guo F, Wang Y . genes: regulators and biomarkers in gynecological cancers. Cancer Biol Med. 2019; 16(3):462-474. PMC: 6743626. DOI: 10.20892/j.issn.2095-3941.2019.0062. View

16.

Lin X, Tan J, Teh A, Lim I, Liew S, MacIsaac J . Cell type-specific DNA methylation in neonatal cord tissue and cord blood: a 850K-reference panel and comparison of cell types. Epigenetics. 2018; 13(9):941-958. PMC: 6284779. DOI: 10.1080/15592294.2018.1522929. View

17.

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

18.

van Dongen J, Langerak A, Bruggemann M, Evans P, Hummel M, Lavender F . Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia. 2003; 17(12):2257-317. DOI: 10.1038/sj.leu.2403202. View

19.

Cox J, Castle P, Behrens C, Sharma A, Wright Jr T, Cuzick J . Comparison of cervical cancer screening strategies incorporating different combinations of cytology, HPV testing, and genotyping for HPV 16/18: results from the ATHENA HPV study. Am J Obstet Gynecol. 2012; 208(3):184.e1-184.e11. DOI: 10.1016/j.ajog.2012.11.020. View

20.

Song L, Liu D, He J, Wang X, Dai Z, Zhao Y . SOX1 inhibits breast cancer cell growth and invasion through suppressing the Wnt/β-catenin signaling pathway. APMIS. 2016; 124(7):547-55. DOI: 10.1111/apm.12543. View