研究动态
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泌尿道膀胱癌分子亚型的转移和复发模式。

Metastasis and recurrence patterns in the molecular subtypes of urothelial bladder cancer.

发表日期:2023 Sep 06
作者: Gottfrid Sjödahl, Pontus Eriksson, Karin Holmsten, Johan Abrahamsson, Mattias Höglund, Carina Bernardo, Anders Ullén, Fredrik Liedberg
来源: Brain Structure & Function

摘要:

泌尿膜的尿液癌经常转移到淋巴结、肺、肝脏和骨骼。已经存在了一种用于分子分类的分类法,但是不知道分子亚型是否对不同器官具有热带性。在这里,我们研究了146例初发转移性疾病或治愈性治疗后复发的患者。我们使用两种转录组方法和免疫染色对原发肿瘤进行分类,并使用排列检验来确定分子亚型在转移性部位的富集和贫化。我们观察到基底/鳞状分子亚型骨转移显著贫化,而尿液状亚型则对骨转移富集。基因组不稳定亚型肺转移贫化,但对包括七例中的六例脑转移在内的非典型部位富集。组织富含基质的原发肿瘤样本与局部复发相关,但与远处部位无关。此外,脑或睾丸转移的比例在全身化疗方案(GC vs MVAC)之间有所不同,表明存在庇护效应。总之,泌尿膜膀胱癌的分子亚型与特定的转移部位显著相关,这表明特定于亚型的分子决定因子可能存在于转移级联的各个步骤中。© 2023 The Authors. 由Wiley & Sons公司代表UICC出版的《国际癌症杂志》。
Urothelial cancer of the urinary bladder frequently metastasizes to lymph-nodes, lungs, liver and bone. A taxonomy for molecular classification exists, but it is unknown if molecular subtypes show tropism for different organs. Here, we study 146 patients with de novo metastatic disease or recurrence after curative treatment. We classify primary tumors using two transcriptomic methods and immunostaining and identify enrichment and depletion of metastatic sites in molecular subtypes using permutation tests. We observed significant depletion of bone metastases in the Basal/squamous molecular subtype, whereas the Urothelial-like subtype entailed an enrichment for metastases to bone. The Genomically unstable subtype was depleted of lung metastases, but enriched for atypical sites, including six out of seven patients with brain metastases. Stroma-rich primary tumor samples were associated with local recurrence, but not with distant sites. Additionally, the proportion with brain or testis metastases differed between systemic chemotherapy regimens (GC vs MVAC) suggesting a sanctuary effect. In conclusion, molecular subtypes of urothelial bladder cancer are significantly associated with specific metastatic sites, suggesting that subtype-specific molecular determinants could exist at various steps in the metastatic cascade.© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.