MicroRNA expression in squamous cell carcinoma and adenocarcinoma of the esophagus: associations with survival.
OBJECTIVE
The dismal outcome of esophageal cancer patients highlights the need for novel prognostic biomarkers, such as microRNAs (miRNA). Although recent studies have established the role of miRNAs in esophageal carcinoma, a comprehensive multicenter study investigating different histologic types, including squamous cell carcinoma (SCC) and adenocarcinoma with or without Barrett's, is still lacking.


METHODS
miRNA expression was measured in cancerous and adjacent noncancerous tissue pairs collected from 100 adenocarcinoma and 70 SCC patients enrolled at four clinical centers from the United States, Canada, and Japan. Microarray-based expression was measured in a subset of samples in two cohorts and was validated in all available samples.


RESULTS
In adenocarcinoma patients, miR-21, miR-223, miR-192, and miR-194 expression was elevated, whereas miR-203 expression was reduced in cancerous compared with noncancerous tissue. In SCC patients, we found elevated miR-21 and reduced miR-375 expression levels in cancerous compared with noncancerous tissue. When comparing cancerous tissue expression between adenocarcinoma and SCC patients, miR-194 and miR-375 were elevated in adenocarcinoma patients. Significantly, elevated miR-21 expression in noncancerous tissue of SCC patients and reduced levels of miR-375 in cancerous tissue of adenocarcinoma patients with Barrett's were strongly associated with worse prognosis. Associations with prognosis were independent of tumor stage or nodal status, cohort type, and chemoradiation therapy.


CONCLUSIONS
Our multicenter-based results highlight miRNAs involved in major histologic types of esophageal carcinoma and uncover significant associations with prognosis. Elucidating miRNAs relevant to esophageal carcinogenesis is potentially clinically useful for developing prognostic biomarkers and identifying novel drug targets and therapies.
Laboratory of Human Carcinogenesis, National Cancer Institute/NIH, Bethesda, Maryland 20892, USA.
Ewy A
EA
Mathé
Giang Huong
GH
Nguyen
Elise D
ED
Bowman
Yiqiang
Y
Zhao
Anuradha
A
Budhu
Aaron J
AJ
Schetter
Rosemary
R
Braun
Mark
M
Reimers
Kensuke
K
Kumamoto
Duncan
D
Hughes
Nasser K
NK
Altorki
Alan G
AG
Casson
Chang-Gong
CG
Liu
Xin Wei
XW
Wang
Nozomu
N
Yanaihara
Nobutoshi
N
Hagiwara
Andrew J
AJ
Dannenberg
Masao
M
Miyashita
Carlo M
CM
Croce
Curtis C
CC
Harris
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016019:Survival Analysis
D035683:MicroRNAs