Argonaute proteins: potential biomarkers for human colon cancer.
BACKGROUND
Although Argonaute proteins are considered to play important roles in stem cell self-renewal, RNA interference (RNAi) and translational regulation, relatively little is known about their functions in human disease. In this study, we investigated the expression of eight members of human Argonaute family in colon cancer and identified their potential roles in tumor development and progression.


METHODS
Antibodies against human Argonaute proteins were prepared by immunizing rabbits with synthetic peptides derived from the sequences of Argonaute members. Then we constructed a tissue microarray containing 75 specimens from colon cancer and 75 specimens from adjacent non-cancer tissue, and assayed eight different proteins (EIF2C1, EIF2C2, EIF2C3, EIF2C4, PIWIL1, PIWIL2, PIWIL3 and PIWIL4) by immunohistochemistry on consecutive formalin-fixed tissue microarray sections.


RESULTS
The expression of EIF2C1-4 and PIWIL1-4 was significantly higher in tumorous tissue than in adjacent tissue. Notably, a significant correlation was observed between the positive expression of EIF2C2, EIF2C3, EIF2C4, PIWIL4 and the presence of distant metastasis. Logistic regression analysis revealed that an increased expression of EIF2C1 and PIWIL2 was significantly associated with occurrence of colon cancer tissue compared with non-cancer tissue.


CONCLUSIONS
Argonaute proteins are overexpressed in colon cancer relative to adjacent non-cancer tissue. The expression of EIF2C2-4 and PIWIL4 appears increased in advanced tumors with distant metastasis, suggesting it may promote tumor invasion. Furthermore, EIF2C1 and PIWIL2 might represent novel colon cancer markers with early diagnostic significance.
Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.
Lan
L
Li
Chaohui
C
Yu
Hengjun
H
Gao
Youming
Y
Li
D000328:Adult; D000368:Aged; D000818:Animals; D060565:Argonaute Proteins; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism*; D018450:Disease Progression; D015852:Eukaryotic Initiation Factor-2 / Q000096:biosynthesis*; D039642:Eukaryotic Initiation Factors; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000378:metabolism*; D034622:RNA Interference; D016601:RNA-Binding Proteins; D011817:Rabbits; D012044:Regression Analysis
C466422:AGO2 protein, human; C517143:AGO3 protein, human; C517144:AGO4 protein, human; D060565:Argonaute Proteins; D014408:Biomarkers, Tumor; D015852:Eukaryotic Initiation Factor-2; D039642:Eukaryotic Initiation Factors; C421088:PIWIL1 protein, human; C556795:PIWIL4 protein, human; D011506:Proteins; D016601:RNA-Binding Proteins