Identification of Downstream Genes of the mTOR Pathway that Predict Recurrence and Progression in Non-Muscle Invasive High-Grade Urothelial Carcinoma of the Bladder.

Identification of Downstream Genes of the mTOR Pathway that Predict Recurrence and Progression in Non-Muscle Invasive High-Grade Urothelial Carcinoma of the Bladder. J Korean Med Sci. 2017 Aug;32(8):1327-1336 Authors: Jin S, Chang IH, Kim JW, Whang YM, Kim HJ, Hong SA, Lee TJ Abstract Microarray analysis was used to investigate the lack of identified mammalian target of rapamycin (mTOR) pathway downstream genes to overcome cross-talk at non-muscle invasive high-grade (HG)-urothelial carcinoma (UC) of the bladder, gene expression patterns, gene ontology, and gene clustering by triple (p70S6K, S6K, and eIF4E) small interfering RNAs (siRNAs) or rapamycin in 5637 and T24 cell lines. We selected mTOR pathway downstream genes that were suppressed by siRNAs more than 2-fold, or were up-regulated or down-regulated by rapamycin more than 2-fold. We validated mTOR downstream genes with immunohistochemistry using a tissue microarray (TMA) of 125 non-muscle invasive HG-UC patients and knockout study to evaluate the synergistic effect with rapamycin. The microarray analysis selected mTOR pathway downstream genes consisting of 4 rapamycin up-regulated genes (FABP4, H19, ANXA10, and UPK3A) and 4 rapamycin down-regulated genes (FOXD3, ATP7A, plexin D1, and ADAMTS5). In the TMA, FABP4, and ATP7A were more expressed at T1 and FOXD3 was at Ta. ANXA10 and ADAMTS5 were more expressed in tumors ≤ 3 cm in diameter. In a multivariate Cox regression model,...
Source: J Korean Med Sci - Category: General Medicine Authors: Tags: J Korean Med Sci Source Type: research