MicroRNA prognostic signature for nodal metastases and survival in XXXX .

@entity1 @entity5 @entity19 @entity3 @entity35 @entity65105 @entity420
BACKGROUND: The incidence of @entity420 is rapidly increasing and is now one of the leading causes of @entity5 death in the western world. MicroRNAs (miRNAs) are small noncoding RNAs that regulate the expression of protein-encoding genes and are involved in the development, progression and prognosis of other @entity5 . We hypothesized that global miRNA expression would predict survival and lymph node involvement in a cohort of surgically resected @entity5 @entity1 . METHODS: The miRNA analysis was performed using a custom Affymetrix microarray with probes for 462 known @entity1 , 2,102 predicted @entity1 , 357 @entity19 , and 238 @entity35 miRNAs. Expression of miRNA was evaluated in 45 @entity5 , and the association of miRNA expression with @entity1 survival and lymph node @entity3 was assessed. The prognostic impact of identified unique miRNAs was verified with quantitative reverse transcriptase polymerase chain reaction. RESULTS: Our data indicate that the expression of individual @entity1 miRNA species is significantly associated with postresection @entity1 survival. Using data from five unique miRNAs, we were further able to generate a combined miRNA expression signature that is associated with @entity1 survival (p=0.005; hazard ratio 3.6) independent of node involvement and overall stage. The expression of three miRNAs ( @entity65105 and miR-199a_3p and _5p) was also associated with the presence of lymph node @entity3 . CONCLUSIONS: These results suggest miRNA expression profiling could provide prognostic utility in staging @entity5 @entity1 and treatment planning with endoscopic and neoadjuvant therapies. The alterations of specific miRNAs may further elucidate steps in the metastatic pathway and allow for development of targeted therapy.
