Correlation of N-myc downstream-regulated gene 1 overexpression with progressive growth of colorectal neoplasm

Abstract

AIM:To study the function of N-myc downstream-regulated gene 1 (NDRG1) in colorectal carcinogenesis and its correlation with tumor lymph node metastasis. METHODS:NDRG1 was detected at its protein level by immunohistochemistry (IHC) and image analysis (IA), and NDRG1 mRNA was detected by in situ hybridization (ISH) in formalin-fixed and paraffin-embedded sections with a total of 190 specimens including 38 normal colorectal mucosae, 31 colorectal adenomas, 45 non-metastatic colorectal carcinomas (CRCs), 38 metastatic primary CRC and subsequently regional lymph nodes respectively. At the same time, the correlations of NDRG1 with sex, age of patients and histological types of colorectal carcinomas were observed. RESULTS: NDRG1 proteins were gradually increased in colorectal carcinogenesis (P<0.05 or P<0.01). There was a significant difference in the expression of NDRG1 between non-metastatic and metastatic CRCs (P<0.05), and the correlation was positive (P<0.01, r s =0.329). However, there was no obvious difference in the expression of NDRG1 between the primary sites of CRCs and that in the metastatic sites of corresponding regional lymph nodes, nor was there an apparent difference in sex, age, and histological types. The expression of NDRG1 mRNA was generally in concordance with that of NDRG1 protein.CONCLUSION: NDRG1 gene may play an important role in colorectal carcinogenesis. In addition, NDRG1 may be a putative tumor metastasis promoter gene and is regarded as one of the molecular biological markers that can forecast early metastasis of CRCs. NDRG1 gene in the metastatic sites of regional lymph nodes may preserve its expression characteristics in the primary sites of CRCs to some extent. The expression of NDRG1 is not affected by sex, age and histological types. The role of NDRG1 in tumor metastatic process can be demonstrated by in vivo and in vitro.

RNA sequencing reveals widespread transcriptome changes in a renal carcinoma cell line

“…NDRG1 is necessary for p53-mediated caspase activation and apoptosis [ 55 ]. High NDRG1 expression has shown potential as a prognostic biomarker in many types of cancers [ 56 , 57 ], including ccRCC [ 58 ]. Moreover, NDRG1 expression is differentially regulated during diverse physiological and pathological conditions such as hypoxia, cellular differentiation, heavy metal response and neoplasia [ 56 , 59 – 61 ].…”

The metastasis suppressor, NDRG1, inhibits “stemness” of colorectal cancer via down-regulation of nuclear β-catenin and CD44

“…Increasing evidence demonstrates that NDRG1 functions as a metastasis suppressor and potentially could be a novel indicator for CRC prognosis [ 16 , 25 , 52 ]. Although NDRG1 has been defined as a metastasis suppressor gene, it is of interest that NDRG1 mRNA expression was found to be up-regulated in colorectal cancer data from the Cancer Genome Atlas (TCGA) [ 53 ]. In addition, in some tumor-types ( e.g ., hepatocellular carcinoma), NDRG1 was associated with more aggressive phenotypes and a poorer prognosis [ 27 ].…”

Oncogenic but non-essential role of N-myc downstream regulated gene 1 in the progression of esophageal squamous cell carcinoma

“…Besides ESCC 2 it was shown that NDRG1 is upregulated during human and mouse skin carcinogenesis 17 , 18 . Elevated NDRG1 levels in cancerous tissue was also observed in human oral squamous cell carcinoma, 19 cervical adenocarcinoma, 20 renal, 21 colon, 22 and liver cancers 23 , 24 . In these cases, increased NDRG1 was associated with at least one of the following parameters: advanced tumor grade, metastasis, vascular invasion and poor prognosis.…”