Tissue microarray analysis of 560 patients with colorectal adenocarcinoma: high expression of HuR predicts poor survival.
The purpose of this study is to characterize the expression of HuR in colorectal carcinoma and determine its correlation with clinical outcome. Differential expression of HuR has been suggested to be of prognostic significance in carcinomas of the ovaries, stomach, and breast. HuR regulates the expression of a variety of proteins critical to carcinogenesis via the pathways of cell-cycle progress, invasion, and metastasis. Increasing evidence suggests that angiogenic pathways are involved. A tissue microarray consisting of tumors from 560 patients with colorectal adenocarcinoma was analyzed for HuR protein expression using a quantitative, automated immunofluorescent microscopy system (AQUA). Clinical data corresponding to each examined specimen collected through an institutional review board (IRB)-approved protocol were analyzed using chi-squared test, Cox regression, and Kaplan-Meier analysis. Median follow-up was 54 months. Along with tumor stage and overall tumor-node-metastasis (TNM) stage, HuR expression was found to be an independent predictor of survival. In patients in the highest quartile of total HuR expression, survival was 22.8 months less than those in the lower quartiles (40.6 versus 63.4 months, p = 0.04). Furthermore, HuR levels correlate positively with expression of vascular endothelial growth factor (VEGF) and CD31, a marker for vascular endothelium. We conclude that expression of high levels of HuR correlates with features of advanced disease and portends poorer survival in patients with colorectal adenocarcinoma. These results further suggest that HuR exerts its tumorigenic effects through VEGF-mediated angiogenesis and may be a novel therapeutic target in colorectal cancer.
Yoo
Peter S
PS
Department of Surgery, Yale University School of Medicine, New Haven, USA.
Sullivan
Catherine A W
CA
Kiang
Sharon
S
Gao
Wenli
W
Uchio
Edward M
EM
Chung
Gina G
GG
Cha
Charles H
CH
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000378:metabolism*; D001331:Automation; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000378:metabolism*; D015996:Survival Rate; D046888:Tissue Array Analysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D016601:RNA-Binding Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A