Related Experiment Video
Updated: Aug 5, 2026
Optimized Preparation of Whole Murine Tumor-Bearing Lung Tissue for Flow Cytometry and Single-Cell RNA-Sequencing
Published on: May 22, 2026
Dynamic evolution of chaperone-mediated autophagy is associated with tumor microenvironment remodeling and prognostic
Kaihong Han1, Wenyu Han2, Wenyao Xie3
1Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Background:
Lung adenocarcinoma (LUAD) shows prognostic heterogeneity, and tumor-node-metastasis (TNM) staging is limited for individualized management. Chaperone-mediated autophagy (CMA) maintains proteostasis, but its role during adenocarcinoma in situ (AIS)-minimally invasive adenocarcinoma (MIA)-invasive adenocarcinoma (IAC) progression remains unclear.
Methods:
Single-cell RNA sequencing (scRNA-seq) data from GSE189357 and bulk transcriptomes from The Cancer Genome Atlas (TCGA)-LUAD and Gene Expression Omnibus (GEO) cohorts were integrated. CMA activity, cell-cell communication, weighted gene co-expression network analysis (WGCNA), tumor-normal differential expression, machine-learning survival modeling, tumor microenvironment (TME) features, drug sensitivity, and EPC1 function were analyzed.
Results:
CMA-high tumor epithelial cells increased from AIS (58.1%) to MIA (65.7%) but declined in IAC (44.4%; p < 0.001). CMA-low cells preferentially received fibroblast-derived extracellular matrix cues. A CMA-negatively correlated module identified 69 core genes. Random survival forest (RSF) performed best among 117 machine-learning combinations (mean concordance index > 0.873). High-risk patients had worse survival across cohorts, and the risk score was independently associated with overall survival (hazard ratio = 16.013, 95% confidence interval: 9.579-26.768, p < 0.001). High-risk tumors showed proliferative activation and M0 macrophage enrichment, whereas low-risk tumors showed stronger immune-related signaling. EPC1 overexpression suppressed malignant phenotypes in A549 cells.
Conclusion:
CMA dynamics are associated with stromal and immune remodeling during LUAD progression. A CMA-based model provides robust prognostic stratification and may offer a basis for future TME-guided studies.
