Background

Bladder cancer (BC) is the 9^th most common cancer diagnosis worldwide. Low grade (LG) represents 70% of all BCs, characterized by recurrence and rare ability (10–15%) to progress to high grade (HG) and invade. The remaining 30% is high grade (HG), fast invasive BC, which is resistant to therapy. Identifying biomarkers for predicting those tumors able to progress is a key goal for patient outcome improvement. This study focuses on the most promising prognostic markers.

Materials and methods

TP53 and FGFR3 mutational status, Survivin, CK19, CK20, E-cadherin and CD44 gene expression analysis were performed on 66 BCs.

Results

Survivin was found associated to tumor grade (p<0.05). Moreover, Survivin correlated with CD44 in TP53 wild type (p = 0.0242) and FGFR3 wild type (p = 0.0036) tumors. In particular the Survivin-CD44 correlation was associated to HG FGFR3 wild type BCs (p = 0.0045). Unsupervised hierarchical clustering based on gene expression data identified four distinct molecular groups reflecting the patient histology (p = 0.038).

Conclusion

We suggest Survivin, both as a biomarker associated to G3 BCs but negatively related to TP53 mutational status, and as a potential novel therapeutic target.

中文翻译：

---

低度和高度膀胱癌的分子表征

背景

膀胱癌（BC）是全球^第9大最常见的癌症诊断。低品位（LG）占所有BC的70％，其特征是复发和罕见的能力（10–15％）可以发展到高品位（HG）和入侵。剩下的30％是对治疗有抵抗力的高品位（HG），快速浸润性BC。鉴定用于预测那些能够进展的肿瘤的生物标志物是改善患者预后的关键目标。这项研究的重点是最有前途的预后指标。

材料和方法

对66个BCs进行了TP53和FGFR3突变状态，Survivin，CK19，CK20，E-cadherin和CD44基因表达分析。

结果

发现存活蛋白与肿瘤等级相关（p ＜0.05）。此外，Survivin与TP53野生型（p = 0.0242）和FGFR3野生型（p = 0.0036）肿瘤中的CD44相关。特别是，Survivin-CD44相关性与HG FGFR3野生型BC相关（p = 0.0045）。基于基因表达数据的无监督分层聚类确定了反映患者组织学的四个不同分子组（p = 0.038）。

结论

我们建议生存素，既是与G3 BCs相关的生物标志物，但与TP53突变状态负相关，并作为潜在的新型治疗靶标。