MiRNA-21, a Potential Prognostic Marker for Human Gastric Cancer
CD Truong, W Feng, W Li, T Khoury, S Alrawi, J Yao, K Xie, S Rossi, G Calin, D Tan. The University of Texas MD Anderson Cancer Center, Houston, TX
Background: MicroRNAs (miRNAs) are small regulatory RNA molecules. Recently, they have been identified in the progression of various cancers. Differential expressions of miRNA-21 (miR-21) and miRNA-29 (miR-29) have been reported and confirmed in lung, colon, and breast cancers. However, little is known regarding the expression patterns and role of miRNAs in gastric cancer.
Design: Human gastric cancer samples (n=54) and available paired normal gastric mucosa were evaluated for the expression of miR-21 and miR-29. Total RNA was extracted from microdissection tissue using a modified TRIZOL procedure. RNA (800 ng) was converted to cDNA by priming with a mixture of looped primers to miR-21 and miR-29 (Mega Plex kit, Applied Biosystems) using reverse transcription conditions. Real-time PCR was performed under standard conditions. The optimal internal control was determined by comparing the mean 2-CT of the tumor and normal groups. The relative expression of each miRNA was calculated using the equation 2-CT, where CT = (CTmiRNA CTinternal control). All qRT-PCRs were performed in duplicate, and the data are presented as means + standard errors of the means (SEM). Differential expression of miRNAs was analyzed and correlated with clinicopathological parameters, including age, gender, tumor grade, lymph node involvement, and survival data.
Results: The mean expression of miR-21 in tumor and normal samples were 27.09 and 16.26 (SEM: 22.83 vs. 8.71), respectively. The differential expression of miR-21 in tumor and normal tissue was statistically significant (p=0.0032). miR-21 was overexpressed in 32 of the 54 gastric cancer patients (59.26%). These 32 patients with elevated expression of miR-21 displayed a poorer prognosis (p<0.05) compared to those without miR-21 overexpression. No significant correlation was observed between miR-21 expression and other clinicopathological variables. The mean expression of miR-29 in tumor and normal samples were 0.1852 and 0.2035 (SEM: 0.1831 vs. 0.2013), respectively. There was no differential expression of miR-29 in tumor and normal gastric tissue (p=0.307).
Conclusions: Our study clearly demonstrated that miR-21 was significantly up-regulated in approximately 60% of gastric cancers. The unfavorable clinical outcomes observed in those with miR-21 overexpression suggest that miR-21 is a potential valuable prognostic marker for clinical assessment and management of gastric cancer.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 110, Tuesday Afternoon