BACKGROUND/AIMS: To determine the clinical significance of gene promoter methylation in hepatocellular carcinoma (HCC), we examined in clinical samples the methylation status of those promoters that showed elevated activity in hepatoma cell lines after 5-aza-2'-deoxycytidine treatment. METHODS: Regarding the genes with promoter hypermethylation in the cell lines, their expression levels and methylation status in HCC and non-HCC tissues were assessed by semiquantitive RT-PCR and methylation-specific PCR. To confirm the result, the expression levels and methylation status in 16 additional HCC and non-HCC tissues were assessed. RESULTS: The promoter regions of caveolin 1 (CAV1), cysteine and glycine-rich protein 1 (CSRP1), Kruppel-like factor 6 (KLF6), myosin (light polypeptide 9) (MYL9), and transgelin (TAGLN) were highly methylated in the cell lines. CAV1 and CSRP1 were methylated in HCC more frequently than in non-HCC. KLF6, MYL9, and TAGLN were fully methylated in both HCC and non-HCC. Using additional clinical samples, downregulation of CAV1 and CSRP1 was observed in 38 and 56%, respectively, of the 16 HCC samples and aberrant methylation of CAV1 and CSRP1 was observed in 56% of HCC in both cases. CONCLUSION: CAV1 and CSRP1 were inactivated in HCC by aberrant methylation and they may serve as important biomarkers of malignancy.
BACKGROUND/AIMS: To determine the clinical significance of gene promoter methylation in hepatocellular carcinoma (HCC), we examined in clinical samples the methylation status of those promoters that showed elevated activity in hepatoma cell lines after 5-aza-2'-deoxycytidine treatment. METHODS: Regarding the genes with promoter hypermethylation in the cell lines, their expression levels and methylation status in HCC and non-HCC tissues were assessed by semiquantitive RT-PCR and methylation-specific PCR. To confirm the result, the expression levels and methylation status in 16 additional HCC and non-HCC tissues were assessed. RESULTS: The promoter regions of caveolin 1 (CAV1), cysteine and glycine-rich protein 1 (CSRP1), Kruppel-like factor 6 (KLF6), myosin (light polypeptide 9) (MYL9), and transgelin (TAGLN) were highly methylated in the cell lines. CAV1 and CSRP1 were methylated in HCC more frequently than in non-HCC. KLF6, MYL9, and TAGLN were fully methylated in both HCC and non-HCC. Using additional clinical samples, downregulation of CAV1 and CSRP1 was observed in 38 and 56%, respectively, of the 16 HCC samples and aberrant methylation of CAV1 and CSRP1 was observed in 56% of HCC in both cases. CONCLUSION: CAV1 and CSRP1 were inactivated in HCC by aberrant methylation and they may serve as important biomarkers of malignancy.
Authors: Nuria Martínez-López; Juan L García-Rodríguez; Marta Varela-Rey; Virginia Gutiérrez; David Fernández-Ramos; Naiara Beraza; Ana M Aransay; Karin Schlangen; Juan Jose Lozano; Patricia Aspichueta; Zigmund Luka; Conrad Wagner; Matthias Evert; Diego F Calvisi; Shelly C Lu; José M Mato; María L Martínez-Chantar Journal: Gastroenterology Date: 2012-06-08 Impact factor: 22.682
Authors: Diana Vetter; Michal Cohen-Naftaly; Augusto Villanueva; Youngmin A Lee; Peri Kocabayoglu; Rebekka Hannivoort; Goutham Narla; Josep M Llovet; Swan N Thung; Scott L Friedman Journal: Hepatology Date: 2012-08-27 Impact factor: 17.425
Authors: Yuki Ohi; Han Qin; Chibo Hong; Laure Blouin; Jose M Polo; Tingxia Guo; Zhongxia Qi; Sara L Downey; Philip D Manos; Derrick J Rossi; Jingwei Yu; Matthias Hebrok; Konrad Hochedlinger; Joseph F Costello; Jun S Song; Miguel Ramalho-Santos Journal: Nat Cell Biol Date: 2011-04-17 Impact factor: 28.824
Authors: Arunangshu Das; James D Bortner; Cesar A Aliaga; Aaron Baker; Anne Stanley; Bruce A Stanley; Matthew Kaag; John P Richie; Karam El-Bayoumy Journal: Prostate Date: 2012-08-21 Impact factor: 4.104