The Landscape of Cell Death Processes with Associated Immunogenic and Fibrogenic Effects in Arrhythmogenic Cardiomyopathy
Abstract
:1. Background
2. Methods
2.1. Collection and Processing of RNA-seq Data
2.2. Signature Gene Sets of Cell Death, Immune Cells, and Pathways
2.3. Differentially Expressed Cell Death Signature Genes
2.4. Comprehensive Analysis of Cell Death and Immune Responses Based on ssGSEA
2.5. Identification of Functional Coexpression Modules by WGCNA
2.6. Additional Methods and Statistics
3. Results
3.1. Differentially Expressed Cell Death Signature Genes
3.2. Comparisons and Correlation Analysis of Cell Death Processes
3.3. Relationships between Cell Death and Immune Responses
3.4. Clustering of ARVC Samples Based on Cell Death Scores
3.5. Correlations between Cell Death, Immune Responses, and Fibrosis in ARVC
3.6. Identifying the Functional Coexpression Module
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Cell Death Category | Up-Regulated in ARVC Samples | Down-Regulated in ARVC Samples |
---|---|---|
Immunogenic cell death (n = 30) | PRF1, IL1R1, P2RX7, CASP8, NLRP3, BAX (n = 6) | TNF (n = 1) |
Apoptosis (n = 87) | TNFRSF10C, NTRK1, NFKBIA, IL1R1, PIK3R5, PRKAR2B, BCL2, IL1RAP, CASP8, IKBKB, PIK3CG, AKT3, PIK3CD, CASP3, BAX, APAF1, IRAK4, TP53, AKT1, PRKX, CAPN2 (n = 21) | TNF, PRKACA, BID, AIFM1, CYCS, PIK3R3, TNFRSF10A, CASP9, PRKAR2A, BIRC2, CHUK, XIAP (n = 12) |
Necroptosis (n = 67) | LEF1, HDAC9, PANX1, BACH2, BCL2, CASP8, CYLD, BRAF, HSPA4, USP22, APP (n = 11) | TNF, IDH2, SPATA2, GATA3, ID1, SIRT3 (n = 6) |
Pyroptosis (n = 50) | NLRP6, NLRP7, GZMB, TP63, NLRP1, GSDMB, IL18, CASP8, NLRP3, CASP3, BAX, CASP4, NOD1, PLCG1, TP53 (n = 15) | GSDMC, TNF, PRKACA, CYCS, CASP9, BAK1, CHMP7 (n = 7) |
Necrosis (n = 62) | NLRP6, SLC6A6, BOK, PYGL, CASP8, BAX, TP53, CYLD, OGT (n = 9) | ATG9B, MT3, TNF, SPATA2, PPIF, SLC25A4, MAP3K5, PGAM5, BIRC2, ATG9A, ASAH1, DNM1L (n = 12) |
Ferroptosis (n = 60) | AKR1C2, AKR1C1, CD44, AKR1C3, ALOX5, ZEB1, AIFM2, TP53, CARS (n = 9) | LPCAT3, CS, STEAP3, GOT1, CRYAB, NCOA4, GCLM, ACSL3, ACO1, FDFT1, HMGCR (n = 11) |
Autophagy (n = 35) | ATG7 (n = 1) | ULK3 (n = 1) |
Key TF | Description | p-Value | FDR | List of Overlapped Genes |
---|---|---|---|---|
HIF1A | Hypoxia inducible factor 1, alpha subunit | 0.000005 | 0.0002 | MMP2, RECK, LOX, VIM, TGFB3, NT5E, TWIST2 |
TFAP2C | Transcription factor AP-2 gamma | 0.00006 | 0.001 | MMP2, ESR1, ECM1 |
TP53 | Tumor protein p53 | 0.0004 | 0.006 | TP53, CABLES1, VCAN, TRIM22, ESR1, APAF1, MMP2 |
VHL | Von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase | 0.0005 | 0.006 | SPARC, TCF4, TP53 |
ETV4 | Ets variant 4 | 0.0007 | 0.006 | MMP14, VIM, MMP2 |
STAT3 | Signal transducer and activator of transcription 3 | 0.001 | 0.007 | MMP2, NOX4, AKAP12, TWIST2, TP53, MMP14 |
HDAC2 | Histone deacetylase 2 | 0.001 | 0.007 | COL1A2, IGF1, APAF1 |
LEF1 | Lymphoid enhancer-binding factor 1 | 0.002 | 0.007 | ESR1, TCF4, NT5E |
NCOR1 | Nuclear receptor corepressor 1 | 0.001 | 0.007 | IGF1, ESR1 |
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Lu, W.; Rao, Y.; Li, Y.; Dai, Y.; Chen, K. The Landscape of Cell Death Processes with Associated Immunogenic and Fibrogenic Effects in Arrhythmogenic Cardiomyopathy. J. Cardiovasc. Dev. Dis. 2022, 9, 301. https://doi.org/10.3390/jcdd9090301
Lu W, Rao Y, Li Y, Dai Y, Chen K. The Landscape of Cell Death Processes with Associated Immunogenic and Fibrogenic Effects in Arrhythmogenic Cardiomyopathy. Journal of Cardiovascular Development and Disease. 2022; 9(9):301. https://doi.org/10.3390/jcdd9090301
Chicago/Turabian StyleLu, Wenzhao, Yanfang Rao, Yao Li, Yan Dai, and Keping Chen. 2022. "The Landscape of Cell Death Processes with Associated Immunogenic and Fibrogenic Effects in Arrhythmogenic Cardiomyopathy" Journal of Cardiovascular Development and Disease 9, no. 9: 301. https://doi.org/10.3390/jcdd9090301