title: Hypermethylation of TFPI2 correlates with cervical cancer incidence in the Uygur and Han populations of Xinjiang, China.
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.
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, China.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Pathology, The Sixth People's Hospital of Huizhou City Guangdong, China.
authors.forename: Qiufen
authors.initials: Q
authors.lastname: Tan
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Tao
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Pang
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Liang
authors.affiliation: Key Laboratory for Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine Shihezi, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
mesh_terms: D044466:Asian People / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D016000:Cluster Analysis; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D020022:Genetic Predisposition to Disease; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D015994:Incidence; D009361:Neoplasm Invasiveness; D011379:Prognosis; D011401:Promoter Regions, Genetic; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000201:enzymology / Q000208:ethnology / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D006023:Glycoproteins; C021240:tissue-factor-pathway inhibitor 2
keywords: HPV16; Han; TFPI2; Uygur; cervical cancer; methylation