Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0023890 (
cirrhosis
)
42,195
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide and its prognosis is poor. Novel targets for treating recurrence and progression along with associated biomarkers are urgently required. In this study, the expression and regulatory mechanism of
DENN/MADD domain containing 2D
(
DENND2D
) were investigated in an attempt to identify a tumor suppressor gene for HCC regulated by silencing through promoter hypermethylation. The levels of
DENND2D
expression in HCC cell lines and surgical specimens were determined using a quantitative polymerase chain reaction assay and the relationship between the expression levels of
DENND2D
mRNA and clinicopathological factors was evaluated. The expression and distribution of
DENND2D
were determined using immunohistochemistry. DNA methylation analysis was performed to determine the regulatory mechanisms of
DENND2D
expression in HCC. Most HCC cell lines (89%) and surgical specimens (78%) expressed lower levels of
DENND2D
mRNA compared with normal liver tissue. In contrast, there was no significant difference in the expression levels of
DENND2D
mRNA between normal tissues of HCC patients with and without
cirrhosis
. The expression patterns of
DENND2D
protein and mRNA were consistent. Patients with significantly lower levels of
DENND2D
mRNA in HCC tissues had remarkably earlier recurrences after hepatectomy and their prognosis worsened. The
DENND2D
promoter was methylated in eight out of nine HCC cell lines and DNA demethylation reactivated
DENND2D
mRNA expression. Hypermethylation of
DENND2D
was frequently detected in HCC tissues (75%) and was significantly associated with downregulation of
DENND2D
mRNA expression.
DENND2D
is a candidate tumor suppressor gene that is inactivated by promoter hypermethylation in patients with HCC and may serve as a novel biomarker of early recurrence of HCC.
...
PMID:Downregulation of DENND2D by promoter hypermethylation is associated with early recurrence of hepatocellular carcinoma. 2418 87
