Overexpression of neurone glial‐related cell adhesion molecule is an independent predictor of poor prognosis in advanced colorectal cancer

Abstract

A downstream target of the Wnt pathway, neurone glial-related cell adhesion molecule (Nr-CAM) has recently been implicated in human cancer development. However, its role in colorectal cancer (CRC) pathobiology and clinical relevance remains unknown. In this study, we examined the clinical significance of Nr-CAM protein expression in a retrospective series of 428 CRCs using immunohistochemistry and tissue microarrays. Cox proportional hazards regression was used to calculate hazard ratios (HR) of mortality according to various clinicopathological features and molecular markers. All CRC samples were immunoreactive for Nr-CAM protein expression, compared to 10 ⁄ 245 (4%) matched normal tissue (P < 0.0001). Of 428 CRC samples, 97 (23%) showed Nr-CAM overexpression, which was significantly associated with nodal (P = 0.012) and distant (P = 0.039) metastasis, but not with extent of local invasion or tumor size. Additionally, Nr-CAM overexpression was associated with vascular invasion (P = 0.0029), p53 expression (P = 0.036), and peritoneal metastasis at diagnosis (P = 0.013). In a multivariate model adjusted for other clinicopathological predictors of survival, Nr-CAM overexpression correlated with a significant increase in disease-specific (HR 1.66; 95% confidence interval 1.11-2.47; P = 0.014) and overall mortality (HR 1.57; 95% confidence interval 1.07-2.30; P = 0.

Down-regulated desmocollin-2 promotes cell aggressiveness through redistributing adherens junctions and activating beta-catenin signalling in oesophageal squamous cell carcinoma

“…Several genes that inhibit β‐catenin/TCF‐mediated signalling, including AXIN2 , SOX2 , and TCF7 , were up‐regulated. Importantly, we found that DSC2 down‐regulated two metastasis‐related genes, NrCAM and MMP‐9 . These findings clearly demonstrate an association of DSC2 with β‐catenin signalling, which can subsequently affect cell mobility and invasiveness.…”

“…The accumulation of free, soluble β‐catenin in the cytoplasm and nuclei occurs during the carcinogenesis of oesophageal squamous epithelia . Importantly, in a Wnt‐targeted gene array analysis, we found that DSC2 suppresses cell invasion by down‐regulating the expression of NrCAM and MMP9, two well‐characterized metastasis‐related molecules .…”

CUL4B contributes to cancer stemness by repressing tumor suppressor miR34a in colorectal cancer

“…Among them, NRCAM, the cell surface glycoprotein, has been reported to be significantly associated with nodal and distant metastasis in colon cancer. NRCAM is also an independent marker of poor prognosis among advanced CRC patients 40 . UPK3A, FAM3D, and LCN2, which participate cancer cell metabolisim, were also downregulated in all PDOs after CUL4B ablation.…”

CHL1 and NrCAM are primarily expressed in low grade pediatric neuroblastoma

“…CHL1 can be down-or upregulated in human cancer genesis [13]. An increased expression of NrCAM has been correlated to metastatic development and tumorigenesis in different human cancers [7,14,15]. Moreover, overexpression of NrCAM elevates cancer cell motility and invasiveness in vitro and has been linked to a poor prognosis in adult patients [7,14].…”

“…An increased expression of NrCAM has been correlated to metastatic development and tumorigenesis in different human cancers [7,14,15]. Moreover, overexpression of NrCAM elevates cancer cell motility and invasiveness in vitro and has been linked to a poor prognosis in adult patients [7,14]. Likewise, overexpression of L1 in adults correlates to tumor progression and metastatic dissemination in glioma, melanoma, ovarial and colon carcinomas [12].…”