ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1604609
This article is part of the Research TopicCommunity Series in The Immunosuppressive Tumor Microenvironment and Strategies to Revert its Immune Regulatory Milieu for Cancer Immunotherapy: Volume IIView all 8 articles
High stroma-tumor ratio is associated with immuno-suppressive tumor microenvironment and poor prognosis in bladder cancer
Provisionally accepted
- Nanjing Medical University, Nanjing, China
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Purpose: Bladder cancer (BLCA) is one of the most common urogenital malignancies in the world. The stroma of tumor microenvironment (TME) largely affects the progression of BLCA. However, a stroma-relevant biomarker for predicting BLCA progression is still lacking.We obtained the gene expression profiles and clinical data of The Cancer Genome Atlas (TCGA) datasets via UCSC Xena. Stroma content was evaluated using stromalscore and stroma-tumor ratio (STR)The STR was assessed by two pathologists independently. The stromalscore, derived from the R package "ESTIMATE", was used to calculate the relative proportions of stroma. We performed cell viability assay, wound healing assay and Boyden chamber assay to determine cell behaviors, and utilized a BLCA inhouse cohort to validate our bioinformatics analysis results.Results: Patients with higher stroma showed worse prognosis. We found that high stroma shaped a more immuno-suppressive TME and in BLCA. Next, we found that stroma could predict the molecular subtype and different therapy options in BLCA.High stroma shaped an immune overdrive TME. Cytological experiments revealed that collagen, the main content of stroma, elevates BLCA cell viability, migration and invasion. The BLCA inhouse cohort results also showed high stroma tend to behave worse prognosis with higher PDL1 expression.High stroma shapes a more immuno-suppressive tumor microenvironment and can not only predict the immune phenotypes but also predict the clinical phenotypes in BLCA. High stroma predicts worse prognosis, STR is a biomarker full of prospects for identifying the immunogenicity and immune-therapy probability of BLCA.
Keywords: stroma-tumor ratio, stromal score, Bladder cancer, Collagen, Bioinformatics analysis
Received: 02 Apr 2025; Accepted: 21 Jul 2025.
Copyright: © 2025 Da, Lu, Zhu, Tai, Liu and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yiqiang Da, Nanjing Medical University, Nanjing, China
Hongrui Tai, Nanjing Medical University, Nanjing, China
Yuan Liu, Nanjing Medical University, Nanjing, China
Yichao Zhu, Nanjing Medical University, Nanjing, China
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