Occupational Health & Safety

Biography

Biography: Kiyomi Taniyama

Abstract

Background: Cervical cancer is the second-most common cancer in women worldwide. In Japan, it was the 11th leading cause of\\\\\\\\r\\\\\\\\ndeath from cancer for women in 2008 but there has been a unique increase of cervical cancer incidence among women in the 20-\\\\\\\\r\\\\\\\\n39-year age group in spite of the decrease of it among women over age 40. Aberrant DNA methylation (abMet) is shown to provide\\\\\\\\r\\\\\\\\ndisease biomarkers with great potential applicable to clinical specimens. The authors examined the relationship between the abMet\\\\\\\\r\\\\\\\\nof DLX4 and SIM1 genes and progression of low-grade squamous intraepithelial lesion (LSIL).
\\\\\\\\r\\\\\\\\nMethods: A total of 113 patients were selected from the CCLBC study, in which 11,039 samples were enrolled between October\\\\\\\\r\\\\\\\\n2007 and March 2010 to compare the cytological features of conventional Pap smears and liquid-based cytology specimens using\\\\\\\\r\\\\\\\\nthe ThinPrep method. They were classified into four groups according to their cervical cytology, HPV infection and follow up.\\\\\\\\r\\\\\\\\nCytology samples were examined for abMet of DLX4 and SIM1 genes and their protein expressions. CaSki cells were treated with\\\\\\\\r\\\\\\\\n5-Aza-2´-deoxycytidine (5-aza-dC).
\\\\\\\\r\\\\\\\\nResults: 40 samples in Group 1 were negative for intraepithelial lesion or malignancy. 21 LSILs in Group 2 showed a continuance\\\\\\\\r\\\\\\\\nof LSIL for longer than 365 days, and 12 LSILs in Group 3 showed an up-grading to high-grade (H) SIL+ within 365 days after the\\\\\\\\r\\\\\\\\ndiagnosis of LSIL. 40 in Group 4 were squamous cell carcinoma. All but Group 1 were infected with hrHPV. Significant difference\\\\\\\\r\\\\\\\\nexisted in frequency of abMet between groups 2 and 3 (p=0.044), between groups 3 and 4 (p=0.020) for DLX4, and between\\\\\\\\r\\\\\\\\ngroups 1 and 3 (p=0.0003), as well as between groups 2 and 3 (p=0.005) for SIM1 gene. DLX4 protein expression was significantly\\\\\\\\r\\\\\\\\nreduced in the DLX4abMet positive tissues, as compared to the negative tissues (p=0.008), and 5-aza-dC treatment extracted\\\\\\\\r\\\\\\\\nDLX4 protein expression of CaSki cells in a dose-dependent manner (p<0.005). The LSIL cases with abMet of SIM1 gene or both\\\\\\\\r\\\\\\\\ngenes progressed faster to HSIL+ than others (p = 0.033 or p=0.048).
\\\\\\\\r\\\\\\\\nConclusion: AbMet of DLX4 and SIM1 genes should be a useful and novel progression marker of uterine cervical LSIL with HPV\\\\\\\\r\\\\\\\\ninfection.