Significance of DNA methyltransferase-1 and histone deacetylase-1 in pancreatic cancer.
Epigenetic modifications play an important role during carcinogenesis. The main goal of this study was to examine expression levels of two critical enzymes, DNA methyltransferase-1 (DNMT1) and histone deacetylase-1 (HDAC1), by immunohistochemistry (IHC) in human pancreatic cancer and precancerous lesions: 20 foci containing normal ductal epithelial cells without an inflammatory back-ground (DE), 30 containing ductal epithelial cells with an inflammatory background (DEI), 48 of pancreatic intraepithelial neoplasia-1A (PanIN-1A), 103 of PanIN-1B, 99 of PanIN-2, 30 of PanIN-3, 18 of intraductal papillary mucinous neoplasm A (IPMA), 10 of IPMB, 20 of IPMC, and 54 of pancreatic ductal adenocarcinoma (PDAC). The expression levels of both DNMT1 and HDAC1 increased from normal to precancerous lesions to pancreatic cancer, in a malignancy-dependent manner. Correlations between expression levels and clinicopathological features of the 54 PDAC patients were also analyzed. The expression of DNMT1 significantly correlated with nerve infiltration, degree of tumor differentiation and TNM staging (p<0.05), while that of HDAC1 correlated with proliferative activity, degree of tumor differentiation and TNM staging (p<0.05). Patients with higher expression of DNMT1 and/or HDAC1 had an overall lower survival than those with lower expression (p<0.05). Higher expression of DNMT1 and HDAC1 correlated with advanced stages of the disease and reflect the malignancy of pancreatic carcinoma. They may become new prognostic markers and potential therapeutic targets for pancreatic cancer.
Wang
Wei
W
Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
Gao
Jun
J
Man
Xiao-Hua
XH
Li
Zhao-Shen
ZS
Gong
Yan-Fang
YF
D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000201:enzymology* / Q000473:pathology; D002278:Carcinoma in Situ / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D021441:Carcinoma, Pancreatic Ductal / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002291:Carcinoma, Papillary / Q000201:enzymology* / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000032:analysis*; D005260:Female; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases