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LAMC2+ Epithelial Cells Drive Bladder Cancer Progression and Predict Immunotherapy Response via SERPINB3/STAT3/CD44
Yutong Chen1, Yunzhong Jiang1, Zezhong Yang1
1Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Cancer Science
|August 5, 2026
Summary
Laminin subunit gamma 2 (LAMC2) promotes bladder cancer progression and predicts poor immunotherapy response. Targeting LAMC2 with compounds like diosmetin offers a potential new treatment strategy for bladder cancer.
Area of Science:
- Extracellular matrix biology
- Cancer research
- Urothelial carcinoma studies
Background:
- Laminin subunit gamma 2 (LAMC2) is implicated in various cancers, but its role in bladder cancer (BCa) remains unclear.
- Understanding LAMC2's function is crucial for developing targeted BCa therapies.
Purpose of the Study:
- To investigate the biological role, molecular mechanisms, and therapeutic potential of LAMC2 in bladder cancer.
- To identify LAMC2-associated biomarkers for prognosis and immunotherapy response.
Main Methods:
- Integrated analysis of single-cell RNA sequencing and public datasets (TCGA-BLCA, GSE13507, IMvigor210).
- Bioinformatic analyses including subclustering, pathway enrichment, GSVA, HdWGCNA, and RNA sequencing.
- In vitro and in vivo validation using LAMC2 knockdown, immunohistochemistry, immunofluorescence, and a xenograft model.
- Drug screening via molecular docking and in vitro assays.
Main Results:
- LAMC2 is upregulated in a malignant epithelial cell subgroup of BCa, correlating with higher tumor grade, advanced stage, poor prognosis, and reduced immunotherapy response.
- LAMC2 drives BCa cell proliferation, migration, and invasion via the SerpinB3/STAT3/CD44 signaling pathway.
- Diosmetin effectively suppresses LAMC2-mediated signaling in BCa cells.
Conclusions:
- LAMC2 serves as a potential biomarker for BCa progression and immunotherapy outcomes.
- The SerpinB3/STAT3/CD44 axis is a key downstream pathway regulated by LAMC2 in BCa.
- Diosmetin demonstrates therapeutic promise for targeting LAMC2 in bladder cancer treatment.
