Abstract
BackgroundIt is currently unclear whether a correlation exists between N-myc downstream-regulated gene 2 (NDRG2) expression and oesophageal squamous cell carcinoma (ESCC). The aim of this study was to examine the underlying clinical significance of NDRG2 expression in ESCC patients and to investigate the effects of NDRG2 up-regulation on ESCC cell growth in vitro and in vivo.MethodsImmunohistochemistry was used to determine the level of NDRG2 expressions in ESCC tissue, which was then compared to specific clinicopathological features in the patient and tissue specimens. Factors associated with patient survival were analysed. Moreover, the effects of up-regulating NDRG2 expression on the growth of an ESCC cell line were examined by MTT, colony formation, DNA replication activity and nude mouse model assays.ResultsNotably low expression of NDRG2 in ESCC patients was inversely associated with clinical stage, NM classification, histological differentiation and patients’ vital status (all P < 0.05). ESCC patients expressing high levels of NDRG2 exhibited a substantially higher 5-year overall survival rate than NDRG2-negative patients. Furthermore, NDRG2 over-expression reduced the proliferation, colony formation and DNA replication activity in ESCC cells, as well as inhibiting the growth of ESCC cells in vivo.ConclusionThe present experiments demonstrated that NDRG2 may be a diagnostic and prognostic marker in patients with ESCC, and up-regulation of NDRG2 might act as a promising therapeutic strategy for aggressive ESCC.
Highlights
It is currently unclear whether a correlation exists between N-myc downstream-regulated gene 2 (NDRG2) expression and oesophageal squamous cell carcinoma (ESCC)
Association between decreased expression of NDRG2 and progression of ESCC To further examine whether expression of the NDRG2 protein is linked to the clinical progression of ESCC, the following samples were subjected to IHC staining with a human NDRG2 antibody: 143 paraffin-embedded, archived ESCC tissue samples, including 5 cases of stage I, 64 cases of stage IIA, 23 cases of stage IIB, 38 cases of stage III and 13 cases of stage IV tumors
Statistical analyses showed no relationship between patient gender or age and NDRG2
Summary
It is currently unclear whether a correlation exists between N-myc downstream-regulated gene 2 (NDRG2) expression and oesophageal squamous cell carcinoma (ESCC). Oesophageal squamous cell carcinoma (ESCC) is the most common pathological type in developing nations, in China [2,3,4]. NDRG2, a member of the N-myc downstream-regulated gene family, belongs to the alpha/beta hydrolase superfamily. It was first cloned at our university from a normal human brain cDNA library by subtractive hybridization It has been shown that breast cancer cells have low or undetectable NDRG2 expression, compared with high levels in normal tissues [11]
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