低级别和高级别膀胱癌的分子特征。

Molecular characterization of low grade and high grade bladder cancer.

机构信息

Genetic Unit of Biology Department, University of Pisa, Pisa, Italy.

Department of Pathology, University Hospital of Pisa, Pisa, Italy.

出版信息

PLoS One. 2019 Jan 16;14(1):e0210635. doi: 10.1371/journal.pone.0210635. eCollection 2019.

BACKGROUND

Bladder cancer (BC) is the 9th 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.

背景

膀胱癌（BC）是全球第 9 大常见癌症诊断。低级别（LG）占所有 BC 的 70%，其特征为复发，仅有 10-15%的罕见能力进展为高级别（HG）并侵犯。其余 30%为高级别（HG），快速侵袭性 BC，对治疗有抗性。确定预测那些有进展潜力的肿瘤的生物标志物是改善患者预后的关键目标。本研究集中于最有前途的预后标志物。

材料和方法

对 66 例 BC 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

Survivin 与肿瘤分级相关（p<0.05）。此外，Survivin 在 TP53 野生型（p = 0.0242）和 FGFR3 野生型（p = 0.0036）肿瘤中与 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层次聚类鉴定了四个不同的分子群，反映了患者的组织学（p = 0.038）。