Deepika Singh1, Amisha Bharti2, Dipanjan Biswas3,4, Mallika Tewari3, Amrita Ghosh Kar5, Mumtaz Ahmed Ansari6, Sunita Singh2, Gopeshwar Narayan7. 1. Cancer Genetics Laboratory, Department of Molecular and Human Genetics, Institute of Science, Banaras Hindu University, Varanasi, 221005, India. 2. Department of Zoology, Mahila Mahavidyalaya, Banaras Hindu University, Varanasi, 221005, India. 3. Department of Surgical Oncology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India. 4. Department of Surgical Oncology, Tata Memorial Hospital, Parel, Mumbai, 400012, India. 5. Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India. 6. Department of General Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India. 7. Cancer Genetics Laboratory, Department of Molecular and Human Genetics, Institute of Science, Banaras Hindu University, Varanasi, 221005, India. gnarayan@bhu.ac.in.
Abstract
INTRODUCTION: Down regulation of DLC1 is associated with poor prognosis in many cancers, however, its role in gallbladder cancer (GBC) is still unclear. In present study, we investigated the expression profile and promoter methylation status of DLC1. METHODS: Expression profiles of DLC1 in 55 GBC and their paired adjacent control samples were analyzed through real time RT-PCR and immunohistochemistry. The mRNA data was correlated with clinico-pathological parameters. Promoter hypermethylation was analyzed through MSP. RESULTS: DLC1 shows downregulation in 76.4%, upregulation in 10.9% whereas no change in 12.7% of GBC samples. Its underexpression shows significant correlation with tumor grade and nodal spread. IHC shows cytoplasmic expression of DLC1 in normal as well as tumor samples. IHC result was concordant to mRNA result. Samples having downregulated DLC1 expression show heterozygous methylation in 83.3% of samples and homozygous methylation in 9.5% of samples whereas 7% of samples have no methylation. Kaplan-Meier analysis shows patient with decreased mRNA of DLC1 have significant low mean survival compared to patients with higher mRNA expression of DLC1. CONCLUSION: Our findings suggested that dysregulated expression of DLC1 and its hypermethylation may be one of the events playing roles in tumorigenesis of GBC and may serve as a potential target for development of future GBC gene therapy.
INTRODUCTION: Down regulation of DLC1 is associated with poor prognosis in many cancers, however, its role in gallbladder cancer (GBC) is still unclear. In present study, we investigated the expression profile and promoter methylation status of DLC1. METHODS: Expression profiles of DLC1 in 55 GBC and their paired adjacent control samples were analyzed through real time RT-PCR and immunohistochemistry. The mRNA data was correlated with clinico-pathological parameters. Promoter hypermethylation was analyzed through MSP. RESULTS: DLC1 shows downregulation in 76.4%, upregulation in 10.9% whereas no change in 12.7% of GBC samples. Its underexpression shows significant correlation with tumor grade and nodal spread. IHC shows cytoplasmic expression of DLC1 in normal as well as tumor samples. IHC result was concordant to mRNA result. Samples having downregulated DLC1 expression show heterozygous methylation in 83.3% of samples and homozygous methylation in 9.5% of samples whereas 7% of samples have no methylation. Kaplan-Meier analysis shows patient with decreased mRNA of DLC1 have significant low mean survival compared to patients with higher mRNA expression of DLC1. CONCLUSION: Our findings suggested that dysregulated expression of DLC1 and its hypermethylation may be one of the events playing roles in tumorigenesis of GBC and may serve as a potential target for development of future GBC gene therapy.
Authors: José Lozano; Rosie Xing; Zhenzi Cai; Heather L Jensen; Carol Trempus; Willie Mark; Ron Cannon; Richard Kolesnick Journal: Cancer Res Date: 2003-07-15 Impact factor: 12.701