Da Yiqiang, Lu Zirong, Zhu Zijian, Tai Hongrui, Liu Yuan, Zhu Yichao
The First Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, China.
School of Pediatrics, Nanjing Medical University, Nanjing, Jiangsu, China.
Front Oncol. 2025 Aug 22;15:1604609. doi: 10.3389/fonc.2025.1604609. eCollection 2025.
Bladder cancer (BLCA) is one of the most common urogenital malignancies in the world. The stroma of the tumor microenvironment (TME) largely affects the progression of BLCA. However, a stroma-relevant biomarker for predicting BLCA progression is still lacking.
We obtained gene expression profiles and clinical data from the Cancer Genome Atlas (TCGA) datasets via UCSC Xena. The amount of stroma was evaluated using a stromal score and a stroma-tumor ratio (STR). The STR was independently assessed by two pathologists. The stromal score, derived from the R package "ESTIMATE," was used to calculate the relative proportions of the stroma. We performed cell viability, wound healing, and Boyden chamber assays to determine cell behavior and utilized a BLCA in-house cohort to validate the results of our bioinformatics analysis.
Patients with a higher stromal content showed a worse prognosis. We found that to the high amount of stroma shaped a more immunosuppressive TME in BLCA. Next, we found that stroma could predict molecular subtypes and different therapy options in BLCA. A high stromal content shaped an immune overdrive TME. Cytological experiments revealed that collagen, the main component of the stroma, elevates BLCA cell viability, migration, and invasion. The results from the BLCA in-house cohort also showed that a high stromal content is associated with a worse prognosis and a higher PDL1 expression.
A high stromal content shapes a more immunosuppressive tumor microenvironment and can predict not only the immune phenotypes but also the clinical phenotypes in BLCA. A high stromal content predicts a worse prognosis. STR exhibits great potential as a biomarker for evaluating the immunogenicity of BLCA and its likelihood of responding to immunotherapy.
膀胱癌（BLCA）是世界上最常见的泌尿生殖系统恶性肿瘤之一。肿瘤微环境（TME）的基质在很大程度上影响BLCA的进展。然而，仍缺乏用于预测BLCA进展的与基质相关的生物标志物。
我们通过UCSC Xena从癌症基因组图谱（TCGA）数据集中获取基因表达谱和临床数据。使用基质评分和基质-肿瘤比率（STR）评估基质的量。STR由两名病理学家独立评估。源自R包“ESTIMATE”的基质评分用于计算基质的相对比例。我们进行了细胞活力、伤口愈合和博伊登室试验以确定细胞行为，并利用一个BLCA内部队列来验证我们生物信息学分析的结果。
基质含量较高的患者预后较差。我们发现，在BLCA中，大量的基质形成了一个更具免疫抑制性的TME。接下来，我们发现基质可以预测BLCA的分子亚型和不同的治疗选择。高基质含量形成了一个免疫亢进的TME。细胞学实验表明，基质的主要成分胶原蛋白可提高BLCA细胞的活力、迁移和侵袭能力。BLCA内部队列的结果还表明，高基质含量与较差的预后和较高的PDL1表达相关。
高基质含量形成了一个更具免疫抑制性的肿瘤微环境，不仅可以预测BLCA的免疫表型，还可以预测其临床表型。高基质含量预示着更差的预后。STR作为评估BLCA免疫原性及其对免疫治疗反应可能性的生物标志物具有巨大潜力。
