Background
Methods
Cell lines and reagents
Transgenic mouse and establishment of KRAS-mutant lung cancer models
Reverse transcription, quantitative real-time PCR and Western blot
Clinical Specimens and Immunohistochemistry (IHC) staining
Screening of differentially expressed genes (DEGs) and identification of the abundance of tumor immune infiltration
Phylogenetic analysis of SDPR
Bioinformatics mining of SDPR
Statistical analysis
Results
The discovery of gene expression signature in KRAS-oncogene-driven lung cancer
Structure and phylogenetic conservative analysis of SDPR
SDPR is downregulated in human lung adenocarcinoma, including KRAS-mutant group
Low expression of SDPR is associated with a poor prognosis in NSCLC patients
Clinicopathologic variablea | HR | 95% CI | P value |
---|---|---|---|
a. SDPR expression associations with overall survival in KRAS-mutant patients (GSE72094) using Cox regression | |||
Expression (low vs high) | 0.55 | 0.31–0.98 | 0.04 |
Clinicopathologic variableb | HR | 95% CI | P value |
---|---|---|---|
b. Multivariate survival model in KRAS-mutant patients (GSE72094) using Cox regression | |||
SDPR expression (low vs high) | 0.53 | 0.29–0.96 | 0.04 |
Gender | 0.77 | 0.41–1.45 | 0.42 |
Smoking | 0.75 | 0.37–1.51 | 0.42 |
Pathological stage (I vs II–IV) | 2.05 | 1.13–3.70 | 0.02 |
c. Impaction of SDPR and clinicopathologic characteristics on overall survival | |||
Clinicopathologic variablea | HR | 95% CI | P value |
---|---|---|---|
d. SDPR expression associations with overall survival in lung cancer patients (GSE72094) using Cox regression | |||
SDPR expression (low vs high) | 0.44 | 0.30–0.64 | < 0.001 |
Clinicopathologic variableb | HR | 95% CI | P value |
---|---|---|---|
e. Multivariate survival model using Cox regression | |||
SDPR expression (low vs high) | 0.47 | 0.32–0.70 | < 0.001 |
Gender | 0.55 | 0.38–0.82 | < 0.001 |
Smoking | 0.78 | 0.503–1.21 | 0.26 |
Pathological stage | < 0.001 | ||
Stage I | 0.75 | 0.16–3.54 | 0.71 |
Stage II | 0.25 | 0.12–0.54 | < 0.001 |
Stage III | 0.48 | 0.21–1.07 | 0.07 |
Stage IV | 0.82 | 0.37–1.83 | 0.63 |
f. Impaction of SDPR and clinicopathologic characteristics on overall survival | |||
Construction of competing endogenous RNA (ceRNA) network of SDPR in KRAS-mutant lung adenocarcinoma pathway
Biological enrichment analysis of SDPR downstream pathway
Correlation between SDPR, immune negative regulatory molecules and immune infiltration models
Infiltrates | rho | p | adj.p |
---|---|---|---|
B cell memory_CIBERSORT | 0.14 | 0.00 | 0.00 |
B cell memory_CIBERSORT-ABS | 0.18 | 0.00 | 0.00 |
B cell plasma_XCELL | − 0.21 | 0.00 | 0.00 |
B cell_EPIC | 0.10 | 0.03 | 0.07 |
B cell_MCPCOUNTER | 0.15 | 0.00 | 0.00 |
B cell_QUANTISEQ | 0.12 | 0.01 | 0.02 |
Cancer associated fibroblast_EPIC | − 0.09 | 0.04 | 0.10 |
Cancer associated fibroblast_XCELL | 0.36 | 0.00 | 0.00 |
Common lymphoid progenitor_XCELL | − 0.21 | 0.00 | 0.00 |
Common myeloid progenitor_XCELL | 0.17 | 0.00 | 0.00 |
Endothelial cell_EPIC | 0.51 | 0.00 | 0.00 |
Endothelial cell_MCPCOUNTER | 0.61 | 0.00 | 0.00 |
Endothelial cell_XCELL | 0.47 | 0.00 | 0.00 |
Eosinophil_XCELL | 0.15 | 0.00 | 0.00 |
Granulocyte-monocyte progenitor_XCELL | 0.39 | 0.00 | 0.00 |
Hematopoietic stem cell_XCELL | 0.62 | 0.00 | 0.00 |
Macrophage M0_CIBERSORT | − 0.33 | 0.00 | 0.00 |
Macrophage M0_CIBERSORT-ABS | − 0.22 | 0.00 | 0.00 |
Macrophage M1_CIBERSORT | − 0.12 | 0.01 | 0.03 |
Macrophage M1_QUANTISEQ | 0.24 | 0.00 | 0.00 |
Macrophage M2_CIBERSORT | 0.22 | 0.00 | 0.00 |
Macrophage M2_CIBERSORT-ABS | 0.38 | 0.00 | 0.00 |
Macrophage M2_QUANTISEQ | 0.40 | 0.00 | 0.00 |
Macrophage M2_XCELL | 0.29 | 0.00 | 0.00 |
Macrophage_EPIC | 0.14 | 0.00 | 0.01 |
Macrophage_TIMER | 0.19 | 0.00 | 0.00 |
Macrophage_XCELL | 0.10 | 0.03 | 0.07 |
Mast cell activated_CIBERSORT | 0.38 | 0.00 | 0.00 |
Mast cell activated_CIBERSORT-ABS | 0.42 | 0.00 | 0.00 |
Mast cell resting_CIBERSORT | − 0.23 | 0.00 | 0.00 |
Mast cell resting_CIBERSORT-ABS | − 0.20 | 0.00 | 0.00 |
Mast cell_XCELL | 0.32 | 0.00 | 0.00 |
MDSC_TIDE | − 0.50 | 0.00 | 0.00 |
Monocyte_CIBERSORT | 0.34 | 0.00 | 0.00 |
Monocyte_CIBERSORT-ABS | 0.40 | 0.00 | 0.00 |
Monocyte_QUANTISEQ | − 0.22 | 0.00 | 0.00 |
Monocyte_XCELL | 0.18 | 0.00 | 0.00 |
Myeloid dendritic cell activated_CIBERSORT | 0.13 | 0.00 | 0.01 |
Myeloid dendritic cell activated_CIBERSORT-ABS | 0.17 | 0.00 | 0.00 |
Myeloid dendritic cell activated_XCELL | 0.15 | 0.00 | 0.00 |
Myeloid dendritic cell resting_CIBERSORT | 0.13 | 0.00 | 0.01 |
Myeloid dendritic cell resting_CIBERSORT-ABS | 0.17 | 0.00 | 0.00 |
Myeloid dendritic cell_MCPCOUNTER | 0.29 | 0.00 | 0.00 |
Myeloid dendritic cell_QUANTISEQ | − 0.19 | 0.00 | 0.00 |
Myeloid dendritic cell_TIMER | 0.17 | 0.00 | 0.00 |
Myeloid dendritic cell_XCELL | 0.29 | 0.00 | 0.00 |
Neutrophil_MCPCOUNTER | 0.33 | 0.00 | 0.00 |
Neutrophil_QUANTISEQ | 0.18 | 0.00 | 0.00 |
Neutrophil_TIMER | 0.11 | 0.01 | 0.03 |
NK cell activated_CIBERSORT-ABS | 0.09 | 0.04 | 0.10 |
NK cell_EPIC | − 0.10 | 0.03 | 0.07 |
Plasmacytoid dendritic cell_XCELL | − 0.15 | 0.00 | 0.00 |
T cell CD4 + (non-regulatory)_XCELL | 0.09 | 0.04 | 0.08 |
T cell CD4 + effector memory_XCELL | 0.12 | 0.01 | 0.02 |
T cell CD4 + memory activated_CIBERSORT | − 0.24 | 0.00 | 0.00 |
T cell CD4 + memory activated_CIBERSORT-ABS | − 0.23 | 0.00 | 0.00 |
T cell CD4 + memory resting_CIBERSORT | 0.28 | 0.00 | 0.00 |
T cell CD4 + memory resting_CIBERSORT-ABS | 0.37 | 0.00 | 0.00 |
T cell CD4 + Th1_XCELL | − 0.38 | 0.00 | 0.00 |
T cell CD4 + Th2_XCELL | − 0.38 | 0.00 | 0.00 |
T cell CD4 + _EPIC | 0.30 | 0.00 | 0.00 |
T cell CD8 + naive_XCELL | − 0.21 | 0.00 | 0.00 |
T cell CD8 + _CIBERSORT-ABS | 0.16 | 0.00 | 0.00 |
T cell CD8 + _EPIC | 0.24 | 0.00 | 0.00 |
T cell CD8 + _TIMER | 0.17 | 0.00 | 0.00 |
T cell follicular helper_CIBERSORT | − 0.11 | 0.01 | 0.03 |
T cell regulatory (Tregs)_CIBERSORT | − 0.17 | 0.00 | 0.00 |
T cell regulatory (Tregs)_QUANTISEQ | 0.34 | 0.00 | 0.00 |