Medicines Discovery Catapult, Alderly Park, Cheshire, UK.
Division of Cancer Sciences, University of Manchester, Manchester, UK.
Commun Biol. 2024 Jun 18;7(1):737. doi: 10.1038/s42003-024-06426-9.
Muscle invasive bladder cancer (MIBC) is a molecularly diverse disease with varied clinical outcomes. Molecular studies typically employ bulk sequencing analysis, giving a transcriptomic snapshot of a section of the tumour. However, tumour tissues are not homogeneous, but are composed of distinct compartments such as the tumour and stroma. To investigate the molecular profiles of bladder cancer, whilst also maintaining the spatial complexity of the tumours, we employed whole transcriptome Digital Spatial Profiling (DSP). With this method we generated a dataset of transcriptomic profiles of tumour epithelium, stroma, and immune infiltrate. With these data we investigate the spatial relationship of molecular subtype signatures and ligand signalling events. We find that Basal/Squamous and Classical subtypes are mostly restricted to tumour regions, while the stroma-rich subtype signatures are abundant within the stroma itself. Additionally, we identify ligand signalling events occurring between tumour, stroma, and immune infiltrate regions, such as immune infiltrate derived GPNMB, which was highly correlated with VEGFA expression within the tumour. These findings give us new insights into the diversity of MIBC at a molecular level and provide a dataset with detailed spatial information that was not available before in bladder cancer research.
肌层浸润性膀胱癌 (MIBC) 是一种分子多样性疾病，具有不同的临床结果。分子研究通常采用批量测序分析，对肿瘤的一部分进行转录组快照分析。然而，肿瘤组织不是均匀的，而是由不同的区域组成，如肿瘤和基质。为了研究膀胱癌的分子特征，同时保持肿瘤的空间复杂性，我们采用了全转录组数字空间分析 (DSP)。通过这种方法，我们生成了肿瘤上皮、基质和免疫浸润的转录组特征数据集。利用这些数据，我们研究了分子亚型特征和配体信号事件的空间关系。我们发现基底/鳞状和经典亚型主要局限于肿瘤区域，而富含基质的亚型特征则在基质本身中大量存在。此外，我们还鉴定了发生在肿瘤、基质和免疫浸润区域之间的配体信号事件，例如源自免疫浸润的 GPNMB，它与肿瘤中 VEGFA 的表达高度相关。这些发现为我们提供了在分子水平上对 MIBC 多样性的新认识，并提供了以前在膀胱癌研究中无法获得的具有详细空间信息的数据集。
