Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Currently at Department of Urology, The University of Toledo Medical Center, Toledo, Ohio.
J Urol. 2021 Sep;206(3):548-557. doi: 10.1097/JU.0000000000001788. Epub 2021 Apr 21.
We compared upper tract urothelial carcinoma (UTUC) and bladder urothelial carcinoma (BUC) in same-patient metachronous UTUC and synchronous UTUC and BUC using next-generation sequencing.
Consecutive untreated same-patient samples of UTUC and BUC were macrodissected from unstained formalin-fixed, paraffin-embedded slides after quality control. Samples were divided into 4 groups: 1) UTUC-metachronous BUC, 2) BUC-metachronous UTUC, 3) synchronous UTUC-BUC, 4) UTUC without BUC. Exclusions were inadequate clinical data or histological tumor purity <30%. Whole transcriptome RNA sequencing was performed. After quality assessment, gene expression clusters using unsupervised hierarchical consensus clustering and correlation with pertinent clinicopathologic variables, a prior RNASeq data set and other published data were performed.
RNAseq was performed on 95 samples (UTUC=61, BUC=34) from 40 untreated patients. Unsupervised consensus clustering segregated the tumors into 2 clusters that were enriched with BASE47 basal-like or luminal-like gene expression. Almost two-thirds (61.9%) of Group 2 tumors were basal-like, while the majority of Groups 1, 3, 4 (80.6%, 70.0% and 69.6%, respectively) were luminal-like (p=0.017). Further analyses revealed that the differences in basal-like and luminal-like gene expression were associated with differential fibroblast and immune cell gene expression signatures. In all, 87.5% of metachronous tumors maintained subtype membership.
Gene expression analysis of same-patient metachronous UTUC-BUC suggests that the majority of mUTUC developing after BUC appear more basal-like, while synchronous and initial UTUC tumors appear luminal-like. Metachronous tumors largely maintain molecular subtype membership of the initial tumor regardless of chronologic development or anatomical origin.
我们通过下一代测序技术比较了同一患者的上尿路尿路上皮癌（UTUC）和膀胱尿路上皮癌（BUC）的异时性 UTUC 和同步性 UTUC 和 BUC。
连续未经治疗的同一患者 UTUC 和 BUC 样本从未染色的福尔马林固定、石蜡包埋切片中通过质量控制进行宏观解剖。样本分为 4 组：1）UTUC-异时性 BUC，2）BUC-异时性 UTUC，3）同步性 UTUC-BUC，4）无 BUC 的 UTUC。排除标准为临床数据不足或组织学肿瘤纯度<30%。进行全转录组 RNA 测序。经过质量评估后，采用无监督层次共识聚类和与相关临床病理变量的相关性，对基因表达簇进行了分析，并与之前的 RNASeq 数据集和其他已发表的数据进行了比较。
对 40 名未经治疗患者的 95 个样本（UTUC=61，BUC=34）进行了 RNAseq 分析。无监督共识聚类将肿瘤分为 2 个簇，这些簇富含 BASE47 基底样或管腔样基因表达。大约三分之二（61.9%）的第 2 组肿瘤为基底样，而第 1、3、4 组（分别为 80.6%、70.0%和 69.6%）的大多数肿瘤为管腔样（p=0.017）。进一步的分析表明，基底样和管腔样基因表达的差异与不同的成纤维细胞和免疫细胞基因表达特征有关。总之，87.5%的异时性肿瘤保持了亚型成员身份。
对同一患者的异时性 UTUC-BUC 的基因表达分析表明，大多数在 BUC 之后发展的 mUTUC 表现出更基底样，而同步性和初始性 UTUC 肿瘤表现出管腔样。异时性肿瘤无论其发生的时间顺序或解剖学起源如何，很大程度上都保持了初始肿瘤的分子亚型成员身份。
