Interaction network analysis of differentially expressed genes and screening of cancer marker in the urine of patients with invasive bladder cancer

摘要

Objective: To detect the expression profile of bladder cancer and to delineate the interaction network of these genes in invasive bladder cancer. Methods: A total of 126 differentially expressed genes were identified, and input into STRING online database to delineate interaction network. The network data were screened with central nodes. The expression of genes with the most evident change in the exfoliated cells of urine was detected. RNA markers with over-expression in stage Ta tumor and/or Tsub1/sub to Tsub4/sub tumors but low expression in blood or inflammatory cells were characterized. Results: On the basis of assay of 21,639 whole-genome oligonucleotide microarray, a total of 126 differentially expressed genes were identified, of which 69 had up-regulated expression and 57 had down-regulated expression. STRING screening showed there were interactions among 103 genes in the bladder cancer which formed a complex network. A total of 23 central nodes were screened with Cytoscape and are involved in multiple signaling pathways related to tumorigenesis. The test specificity was 80% for the 30 control patients with urinary tract infections. The combination of BLCA-4 and HOXA13 could distinguish between low and high grade tumors, with specificity and sensitivity of 80%. Conclusion: The interaction network of differentially expressed genes, especially the central nodes of this network, can provide evidence for the early diagnosis and molecular targeted therapy of invasive bladder cancer, and combined detection of IGF-1, hTERT, BLCA-4 and HOXA13 genes is helpful to evaluate BTCC at different stages.