Leukocyte adhesion-GPCR EMR2 is aberrantly expressed in human breast carcinomas and is associated with patient survival

Abstract

Abstract. EGF-like module containing mucin-like hormone receptor 2 (EMR2) is a leukocyte-restricted adhesion G protein-coupled receptor. Aberrant expression of EMR2 and its highly homologous molecule CD97 have been reported in various human cancers. Herein, we investigate the expression of EMR2 in neoplastic breast human tissue and its relationship with patient survival. EMR2 expression in normal and neoplastic breast tissue was assessed by immunohistochemistry in sections from 10 normal controls and microarrayed tissue cores from 69 cases of ductal carcinoma in situ (DCIS) and 272 invasive carcinomas. The pattern and intensity of staining was correlated with the clinicopathological characteristics of each case and the disease outcome. While absent in normal breast epithelium, EMR2 was significantly up-regulated in the cytoplasmic and nuclear compartments of both DCIS and invasive carcinoma, with invasive samples displaying significantly higher expression levels compared with in situ disease. In invasive disease, EMR2 cytoplasmic expression was significantly associated with higher tumour grade but not with patient age, nodal status, tumour size, estrogen receptor expression, relapse-free or overall survival. In contrast, EMR2 nuclear expression correlated negatively with higher tumour grade. Of note, EMR2 nuclear expression was associated with longer relapse-free survival as well as overall survival. This study indicates that EMR2 is expressed in neoplastic breast epithelium and suggests that expression patterns of EMR2 are relevant in breast cancer progression. The association of improved patient survival with higher nuclear expression levels identifies EMR2 as a potential biomarker in patients with invasive breast cancer.

Incorporating inter-relationships between different levels of genomic data into cancer clinical outcome prediction

“…In addition, genetic and epigenetic regulation of the SLC22A3 gene associated with prostate cancer was well described [63] and the potential role of SLC22A3 as one of the members of FRA6E in ovarian cancer was also investigated [64]. EGF-like module containing mucin-like hormone receptor 2 (EMR2) is associated with survival in breast cancer [65]. Among miRNAs with a large number of edges, hsa-miR-146a is well known as a common mechanism of miRNA activity in cancer cell, which is trans-activated by the NF-kB pathway and negatively feeds back on this signaling cascade by targeting two upstream activators of the pathway, IRAK1 and TRAF6 [66].…”

Adhesion GPCRs in Tumorigenesis

“…Aberrant expression of EMR2 protein is reported in breast carcinomas. It is associated with poor patient survival [64]. EMR2 is found upregulated in glioblastoma, in particular in the mesenchymal subtype [74], and is associated with poor overall survival and an invasive phenotype [75].…”

Serum MicroRNA profile in patients with colon adenomas or cancer

“…These miRNAs may be specific diagnostic biomarkers for colon cancer and further clinical investigations are needed. What’s important, it was the first time to report that miR-4463, miR-5704, and miR-371b-3p, miR-1247-5p, miR-1293, miR-548at-5p was associated with colon cancer, excepting miR-107 [41, 42] and miR-139-3p [43, 44]. …”