Abstract
Purpose
Mitophagy and aging (MiAg) are very important pathophysiological mechanisms contributing to tumorigenesis. MiAg-related genes have prognostic value in lung adenocarcinoma (LUAD). However, prognostic, and immune correlation studies of MiAg-related genes in LUAD are lacking.
Methods
MiAg differentially expressed genes (DEGs) in LUAD were obtained from public sequencing datasets. A prognostic model including MiAg DEGs was constructed according to patients divided into low- and high-risk groups. Gene Ontology, gene set enrichment analysis, gene set variation analysis, CIBERSORT immune infiltration analysis, and clinical characteristic correlation analyses were performed for functional annotation and correlation of MiAgs with prognosis in patients with LUAD.
Results
Seven MiAg DEGs of LUAD were identified: CAV1, DSG2, DSP, MYH11, NME1, PAICS, PLOD2, and the expression levels of these genes were significantly correlated (P < 0.05). The RiskScore of the MiAg DEG prognostic model demonstrated high predictive ability of overall survival of patients diagnosed with LUAD. Patients with high and low MiAg phenotypic scores exhibited significant differences in the infiltration levels of eight types of immune cells (P < 0.05). The multi-factor DEG regression model showed higher efficacy in predicting 5-year survival than 3- and 1-year survival of patients with LUAD.
Conclusions
Seven MiAg-related genes were identified to be significantly associated with the prognosis of patients diagnosed with LUAD. Moreover, the identified MiAg DEGs might affect the immunotherapy strategy of patients with LUAD.
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Data availability
The datasets generated during and/or analysed during the current study are available in the TCGA (https://portal.gdc.cancer.gov/) and GEO (GSE10072, GSE30219 and GSE3141).
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Acknowledgements
This work was supported by National Key R&D Program of China (Grant Nos. 2020YFE02022200).
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This work was supported by National Key R&D Program of China (Grant no. 2020YFE02022200).
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Data collection: XM, WS; Data analysis: XM, WS, ML; Manuscript writing: XM, BZ; Study design: YG, XM.
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432_2023_5390_MOESM1_ESM.tif
Supplementary file1Fig. S1 TCGA-LUAD dataset normalization. (a-b) Boxplot of TCGA-LUAD dataset pre (a) and post (b) normalization. (c-d) Principal component analysis plot of TCGA-LUAD dataset pre (c) and post (d) normalization (TIF 3930 KB)
432_2023_5390_MOESM2_ESM.tif
Supplementary file2Fig. S2 Normalization of the GEO LUAD datasets. (a-b) Boxplot of the GSE10072 dataset before (A) and after (B) normalization. (c-d) Boxplot of the GSE30219 dataset pre (c) and post (d) normalization (TIF 3234 KB)
432_2023_5390_MOESM3_ESM.tif
Supplementary file3Fig. S3 Correlation analysis of mitophagy-aging differentially expressed genes (MiAg DEGs) in lung adenocarcinoma (LUAD) in the (a) GSE30219 and (d) GSE10072dataset. (a) Correlation heat map of MiAg DEGs. Correlation scatter plots of MiAg DEGs MYH11 and NME1 (b-c) and NME1 and PAICS (e-f). ns, not significant (P ≥ 0.05); *P < 0.05; **P < 0.01; ***P < 0.001. In a correlation scatter diagram, the strength of the correlation coefficient (r) is determined by its absolute value. Absolute value > 0.8: strong correlation; 0.5–0.8: moderately correlated; 0.3–0.5: weak correlation; <0.3 weak and irrelevant correlation (TIF 718 KB)
432_2023_5390_MOESM4_ESM.tif
Supplementary file4Fig. S4 Differential expression analysis of mitophagy-aging differentially expressed genes (MiAg DEGs) in the GSE10072 dataset. (a) Group comparison chart of the differential expression analysis of MiAg DEGs. (b–h) Receiver operating characteristic curve of MiAg DEGs CAV1 (b), DSG2 (c), DSP (d), MYH11 (e), NME1 (f), PAICS (g), PLOD2 (h). ns, not significant (P ≥ 0.05); *P < 0.05; **P < 0.01; ***P < 0.001. The closer the area under the curve (AUC) is to 1, the better the diagnostic effect. AUC = 0.5–0.7: low accuracy; 0.7–0.9: certain accuracy; >0.9: high accuracy (TIF 939 KB)
432_2023_5390_MOESM5_ESM.tif
Supplementary file5Fig. S5 Differential expression analysis of mitophagy-aging-related differentially expressed genes (MiAg DEGs) in the GSE30219 dataset. (a) Group comparison chart of the differential expression analysis of MiAg DEGs. (b–h) Receiver operating characteristic curve results of MiAg DEGs CAV1 (b), DSG2 (c), DSP (d), MYH11 (e), NME1 (f), PAICS (g), PLOD2 (h). ns, not significant (P ≥ 0.05); *P < 0.05; **P < 0.01; ***P < 0.001. The closer the area under the curve (AUC) value is to 1, the better the diagnostic effect. AUC = 0.5–0.7: low accuracy; 0.7–0.9: certain accuracy; > 0.9: high accuracy (TIF 935 KB)
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Meng, X., Song, W., Zhou, B. et al. Prognostic and immune correlation analysis of mitochondrial autophagy and aging-related genes in lung adenocarcinoma. J Cancer Res Clin Oncol 149, 16311–16335 (2023). https://doi.org/10.1007/s00432-023-05390-x
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DOI: https://doi.org/10.1007/s00432-023-05390-x