Single-cell stemness analysis highlights Midkine-LRP1 pathway and identifies new bladder cancer subtypes

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Bladder cancer (BC) is a prevalent malignancy globally.
• Tumor stem cells significantly influence BC recurrence and progression.
• Understanding stem cell interactions is crucial for improving BC management.

Purpose of the Study:

• Identify bladder cancer stem cells and their associated genes.
• Investigate stem cell communication pathways.
• Develop a prognostic model for bladder cancer.

Main Methods:

• Single-cell RNA sequencing to identify tumor stem cells.
• Differential gene expression analysis to find high-risk stemness genes (HRSGs).
• Construction of a prognostic risk model based on stemness genes and patient stratification.

Main Results:

• Identified 91 upregulated genes in BC stem cells; 67 defined as HRSGs.
• The MDK-LRP1 axis was identified as a key communication pathway involving 31 HRSGs.
• A risk model stratified patients into two stemness clusters (ST cluster A and B), with ST cluster B indicating poorer prognosis.
• ACTN1 was identified as a key gene associated with poor survival and advanced BC stages.

Conclusions:

• Stem cell-driven progression and communication pathways like MDK-LRP1 are critical in bladder cancer.
• A novel prognostic model based on HRSGs effectively stratifies BC patients.
• ACTN1 and potential Midkine interactions present therapeutic targets for bladder cancer.