Hypermethylation of TFPI2 Correlates with Cervical Cancer Incidence in the Uygur and Han Populations of Xinjiang, China

Overview

Journal Int J Clin Exp Pathol

Specialty Pathology

Date 2015 May 15

PMID 25973077

Citations 15

Authors

Yuling Dong

Qiufen Tan

Lin Tao

Xiaolin Pan

Lijuan Pang

Weihua Liang

Wei Liu

Wenjie Zhang

Feng Li

Wei Jia

Affiliations

Soon will be listed here.

Abstract

Tissue factor pathway inhibitor 2 (TFPI2) is a Kunitz-type serine proteinase inhibitor, which plays an important role in the etiology of human malignancies. DNA methylation is a common epigenetic modification of the genome that is involved in regulating many cellular processes. In addition to human papilloma virus (HPV) infection, DNA methylation may play a role in the carcinogenesis of cervical cancer. Methylation of 22 CpG sites in the promoter region of the TFPI2 gene was detected by MassARRAY spectrometry and a gene mass spectrogram was drawn using MALDI-TOF MS. HPV16 was detected by PCR. We show that aberrant methylation of TFPI2 is present in a higher proportion of invasive cervical carcinoma (ICC) clinical samples as compared to normal cervical samples in Uygur and Han. Across the four pathologic lesions of the progression of cervical cancer, ICC showed the highest level of aberrant methylation, and with a stronger correlation between CpG site and lesion grade in Uygur than in Han. Moreover, a difference in TFPI2 methylation between Uygur patients positive and negative for HPV16 infection was observed at CpG_6 (P = 0.028) and CpG_15 (P = 0.007). Altogether, these results indicate that DNA methylation of TFPI2 may play an important role in the carcinogenesis of cervical cancer and that the differential methylation of TFPI2 may at least partially explain the disparity in cervical cancer incidence between Uygur and Han women.

Citing Articles

Tissue factor pathway inhibitor 2 as a serum biomarker for endometrial cancer: a single-center retrospective study.

Uomoto M, Ota Y, Suzuki Y, Yumori A, Narimatsu H, Koizume S BMC Cancer. 2024; 24(1):1058.

PMID: 39192208 PMC: 11351603. DOI: 10.1186/s12885-024-12827-0.

Arsenic Exposure and Cancer-Related Proteins in Urine of Indigenous Bolivian Women.

De Loma J, Gliga A, Levi M, Ascui F, Gardon J, Tirado N Front Public Health. 2020; 8:605123.

PMID: 33381488 PMC: 7767847. DOI: 10.3389/fpubh.2020.605123.

Role of DNA Methylation in the Resistance to Therapy in Solid Tumors.

Romero-Garcia S, Prado-Garcia H, Carlos-Reyes A Front Oncol. 2020; 10:1152.

PMID: 32850327 PMC: 7426728. DOI: 10.3389/fonc.2020.01152.

Two ways of epigenetic silencing of TFPI2 in cervical cancer.

Fullar A, Karaszi K, Hollosi P, Lendvai G, Olah L, Reszegi A PLoS One. 2020; 15(6):e0234873.

PMID: 32559232 PMC: 7304613. DOI: 10.1371/journal.pone.0234873.

Role of extra cellular proteins in gastric cancer progression and metastasis: an update.

Abbaszadegan M, Mojarrad M, Moghbeli M Genes Environ. 2020; 42:18.

PMID: 32467737 PMC: 7227337. DOI: 10.1186/s41021-020-00157-z.

References

Briolat J, Dalstein V, Saunier M, Joseph K, Caudroy S, Pretet J . HPV prevalence, viral load and physical state of HPV-16 in cervical smears of patients with different grades of CIN. Int J Cancer. 2007; 121(10):2198-204. DOI: 10.1002/ijc.22959. View

Fiander A, Hart K, Hibbitts S, Rieck G, Tristram A, Beukenholdt R . Variation in human papillomavirus type-16 viral load within different histological grades of cervical neoplasia. J Med Virol. 2007; 79(9):1366-9. DOI: 10.1002/jmv.20875. View

Hube F, Reverdiau P, Iochmann S, Rollin J, Cherpi-Antar C, Gruel Y . Transcriptional silencing of the TFPI-2 gene by promoter hypermethylation in choriocarcinoma cells. Biol Chem. 2003; 384(7):1029-34. DOI: 10.1515/BC.2003.115. View

Kahn S, Ronnett B, Gravitt P, Gustafson K . Quantitative methylation-specific PCR for the detection of aberrant DNA methylation in liquid-based Pap tests. Cancer. 2008; 114(1):57-64. PMC: 2648805. DOI: 10.1002/cncr.23258. View

Rountree M, Bachman K, Herman J, Baylin S . DNA methylation, chromatin inheritance, and cancer. Oncogene. 2001; 20(24):3156-65. DOI: 10.1038/sj.onc.1204339. View

Lefevre J, Hankins C, Pourreaux K, Voyer H, Coutlee F . Real-time PCR assays using internal controls for quantitation of HPV-16 and beta-globin DNA in cervicovaginal lavages. J Virol Methods. 2003; 114(2):135-44. DOI: 10.1016/j.jviromet.2003.09.003. View

Mayinuer N, Liu F, Zhu K, Dai J, Ayeti S, Wang L . [Relationship between human papillomavirus 16 infection and the expression of p33(ING1b), human telomerase reverse transcriptase in cervical squamous cell carcinoma of Uygur female in Xinjiang Uygur Autonomous Region]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2007; 29(5):592-6. View

Gessler F, Voss V, Seifert V, Gerlach R, Kogel D . Knockdown of TFPI-2 promotes migration and invasion of glioma cells. Neurosci Lett. 2011; 497(1):49-54. DOI: 10.1016/j.neulet.2011.04.027. View

Glockner S, Dhir M, Yi J, McGarvey K, Van Neste L, Louwagie J . Methylation of TFPI2 in stool DNA: a potential novel biomarker for the detection of colorectal cancer. Cancer Res. 2009; 69(11):4691-9. PMC: 3062162. DOI: 10.1158/0008-5472.CAN-08-0142. View

10.

Yang H . Aberrant DNA methylation in cervical carcinogenesis. Chin J Cancer. 2012; 32(1):42-8. PMC: 3845585. DOI: 10.5732/cjc.012.10033. View

11.

Shukla S, Mahata S, Shishodia G, Pande S, Verma G, Hedau S . Physical state & copy number of high risk human papillomavirus type 16 DNA in progression of cervical cancer. Indian J Med Res. 2014; 139(4):531-43. PMC: 4078491. View

12.

Hu J, Sun Q, Li L, Liu C, Chen Y, Zou H . Human leukocyte antigen-DRB1*1501 and DQB1*0602 alleles are cervical cancer protective factors among Uighur and Han people in Xinjiang, China. Int J Clin Exp Pathol. 2014; 7(9):6165-71. PMC: 4203236. View

13.

Flores R, Papenfuss M, Klimecki W, Giuliano A . Cross-sectional analysis of oncogenic HPV viral load and cervical intraepithelial neoplasia. Int J Cancer. 2005; 118(5):1187-93. DOI: 10.1002/ijc.21477. View

14.

Andersson S, Safari H, Mints M, Lewensohn-Fuchs I, Gyllensten U, Johansson B . Type distribution, viral load and integration status of high-risk human papillomaviruses in pre-stages of cervical cancer (CIN). Br J Cancer. 2005; 92(12):2195-200. PMC: 2361820. DOI: 10.1038/sj.bjc.6602648. View

15.

Kisiel J, Yab T, Taylor W, Chari S, Petersen G, Mahoney D . Stool DNA testing for the detection of pancreatic cancer: assessment of methylation marker candidates. Cancer. 2011; 118(10):2623-31. PMC: 3292683. DOI: 10.1002/cncr.26558. View

16.

Rollin J, Iochmann S, Blechet C, Hube F, Regina S, Guyetant S . Expression and methylation status of tissue factor pathway inhibitor-2 gene in non-small-cell lung cancer. Br J Cancer. 2005; 92(4):775-83. PMC: 2361876. DOI: 10.1038/sj.bjc.6602298. View

17.

Zuo Q, Zheng W, Zhang J, Pan Z, Liu Y, Long H . Methylation in the promoters of HS3ST2 and CCNA1 genes is associated with cervical cancer in Uygur women in Xinjiang. Int J Biol Markers. 2014; 29(4):e354-62. DOI: 10.5301/jbm.5000107. View

18.

Chen Y, Ma C, Chen Z, Zhang W . [Clinical significance of miR-143 expression in women with cervical cancer of Uyghur and Han ethnicities, in Xinjiang]. Zhonghua Liu Xing Bing Xue Za Zhi. 2014; 34(11):1120-4. View

19.

Bretz N, Noske A, Keller S, Erbe-Hofmann N, Schlange T, Salnikov A . CD24 promotes tumor cell invasion by suppressing tissue factor pathway inhibitor-2 (TFPI-2) in a c-Src-dependent fashion. Clin Exp Metastasis. 2011; 29(1):27-38. DOI: 10.1007/s10585-011-9426-4. View

20.

Zheng X, Yang A, Pan X, Zheng L, Wang X, Zhou Q . Ethnicity determines association of p53Arg72Pro alleles with cervical cancer in China. Eur J Cancer Prev. 2008; 17(5):460-6. DOI: 10.1097/CEJ.0b013e3282f75f3e. View