Preview

PDF, English Download (4MB) | Terms of use

Abstract

ANLN and TLE2 are associated with cancer patient survival and progression. The impact of their gene expression on survival of patients with MIBC treated with RC and subtype association has not yet been investigated. This study provides in silico and in vitro evidence supporting the prognostic potential of ANLN and TLE2 for patients with MIBC. In the Mannheim cohort, tumors with high ANLN expression were associated with lower OS and DSS, while high TLE2 expression was associated with a favorable OS. The TCGA cohort confirmed that high ANLN and low TLE2 expression was associated with shorter OS and DFS. In both cohorts, multivariable analyses showed ANLN and TLE2 expression as independent outcome predictors. Furthermore, ANLN was more highly expressed in cell lines and patients with the basal subtype, while TLE2 expression was higher in cell lines and patients with the luminal subtype. ANLN and TLE2 are promising biomarkers for individualized BLCA therapy including cancer subclassification and informed MIBC prognosis. These results indicate that developing ANLN and TLE2 as new biomarkers will help to further optimize personalized therapy for these patients. Growing evidence supports the pivotal role of lncRNAs in the regulation of cancer development and progression. Their expression patterns and biological function in MIBC remain elusive. In this study, a decreased expression of lncRNA MIR31HG was found in BLCA cells and tissues, except in the basal subtype. In vitro experiments revealed that knockdown of MIR31HG inhibits cell proliferation, colony formation and migration in BLCA. Survival analysis showed that high expression of MIR31HG was associated with poor OS and DFS in patients with MIBC of basal subtype. Two splice variants of MIR31HG lacking exon 1 (MIR31HGΔE1) and exon 3 (MIR31HGΔE3) were identified to have specific expression patterns in different subtypes of both MIBC cohorts. MIR31HGΔE3 was highly expressed in tumors with basal subtype. After knockdown of splice variants of MIR31HG, cell proliferation and migration assays showed corresponding roles for the full-length transcript. A high expression of MIR31HGΔE1 and MIR31HGΔE3 was associated with worse OS and DFS in the Mannheim cohort. This study demonstrates that MIR31HG and its splice variants could serve as biomarkers for the classification and prognosis prediction of patients with MIBC. Taking together, this thesis provides new insights into studies for the molecular classification and relevance of RNA variants in MIBC.