Abstract Many bladder cancer (BC) patients with early disease are asymptomatic and diagnosed at advanced stage when the therapeutic options are limited. This necessitates the development of reliable predictive molecular biomarkers that will ensure a positive therapeutic response in every patient. The aim of this study was to screen for alterations in gene expression levels related to drug sensitivity and resistance that may be further explored as potential predictive therapeutic biomarkers. Gene expression analysis of the 168 genes from two panels for Cancer drug resistance and metabolism (PAHS004) and Cancer Drug Targets (PAHS507z) was performed. A total of 47 transitorial cell bladder cancer samples of stage pTa, pT1, pT2 were investigated using the pooling method, which allows reducing the effect of biological variation and detecting only significant expression changes. Differential gene expression was calculated using the ΔΔCt method with GPDH as a housekeeping gene. The 4.0-fold change in gene expression was used as the cut-off threshold to determine upregulation or downregulation compared to normal bladder tissue (negative control). Significance of the differences in the expression profiles was assessed by nonparametric one-way analysis of variance (ANOVA) with Dunn’s multiple comparison tests and Mann-Witney test. We demonstrated a correlation of tumor invasion and several up-regulated genes related to chemotherapy resistance. For the first time, this study demonstrated overexpression of CDK8, CDK9, FIGF, HDAC11, IGF1 and PDGFRA genes in muscle-invasive bladder carcinomas. These genes and their proteins could be used as potential biomarkers for bladder cancer progression or prospective therapeutic targets.

中文翻译：

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肌肉侵袭性和非侵袭性膀胱肿瘤的表达谱，用于与耐药性、敏感性和肿瘤进展相关的生物标志物鉴定

摘要 许多早期膀胱癌（BC）患者无症状，在治疗选择有限的情况下被诊断为晚期。这需要开发可靠的预测性分子生物标志物，以确保每位患者都能获得积极的治疗反应。本研究的目的是筛选与药物敏感性和耐药性相关的基因表达水平的变化，这些变化可以作为潜在的预测性治疗生物标志物进一步探索。对来自癌症耐药性和代谢 (PAHS004) 和癌症药物靶标 (PAHS507z) 的两个小组的 168 个基因进行了基因表达分析。使用合并方法研究了总共 47 个 pTa、pT1、pT2 期的膀胱移行细胞癌样本，这允许减少生物变异的影响并仅检测显着的表达变化。差异基因表达使用ΔΔCt方法计算，GPDH作为看家基因。与正常膀胱组织（阴性对照）相比，基因表达的 4.0 倍变化用作确定上调或下调的截止阈值。表达谱差异的显着性通过非参数单向方差分析 (ANOVA) 与 Dunn 多重比较检验和 Mann-Witney 检验进行评估。我们证明了肿瘤侵袭和几个与化疗耐药相关的上调基因的相关性。该研究首次证明了肌层浸润性膀胱癌中 CDK8、CDK9、FIGF、HDAC11、IGF1 和 PDGFRA 基因的过度表达。