Gene expression
Can single-cell plus bulk RNA-seq predict LUAD survival?
Open access · cc by · source: Europe PMC
From 8,170 lung cells and TCGA LUAD bulk data, a six-gene score (CP, GOLM1, CYP4B1, DAPK2, NFIX, FHL2) stratified survival (1-/3-/5-year AUC 0.67/0.67/0.64) and tracked TP53, TMB, and PD-L1.
Study at a glance
- Design
- Computational / modelling — Integrated 10x scRNA-seq (GSE149655) with TCGA bulk RNA-seq; LASSO/Cox risk model validated in GSE31210 and GSE13213.
- N
- N=8170 · 8,170 QC’d cells from 4 scRNA-seq samples (2 LUAD, 2 normal); bulk model built in TCGA and validated in two GEO LUAD cohorts.
- Population
- Human LUAD and normal lung single-cell samples plus TCGA/GEO lung adenocarcinoma transcriptomes.
- Outcome
- Six-gene overall-survival risk score, NMF subtypes, TMB/PD-L1 and immune features.
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Key findings
High-risk patients had worse OS. Risk was independent of usual clinicopathology. High-risk tumors had more TP53 mutation, higher TMB, PD-L1 upregulation, and cell-cycle/DNA-replication programs. NMF found two bulk subtypes with different immune classes.
Methodology
Integrated GSE149655 10x scRNA-seq (UMAP, 13 clusters, 9 cell types), found DEGs, WGCNA (329 genes), NMF subtypes in TCGA, then univariate Cox → LASSO → multivariate Cox to build a median-split risk score, validated in GSE31210 and GSE13213.
Limitations
Retrospective public data, modest AUCs (~0.64–0.67), and scRNA n=4 samples; the score is not a prospective clinical test and does not prove the six genes cause LUAD.
How this study connects
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