Citation: | QIAN Han, CAO Mengfei, LYU Shumei, YUAN Wei. Bioinformatics study on potential biomarkers of myocardial infarction[J]. Journal of Clinical Medicine in Practice, 2023, 27(3): 21-28, 34. DOI: 10.7619/jcmp.20223235 |
To find potential biomarkers of myocardial infarction from the perspective of peripheral blood mononuclear cells (PBMCs).
The sequencing dataset GSE59867 of peripheral blood mononuclear cells from patients with myocardial infarction was downloaded from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network (WGCNA) and differentially expressed genes (DEGs) were used to investigate the biological changes during process of myocardial infarction and to find common genes. Common transcription factors for these genes were predicted. Finally, hub genes were identified by LASSO regression analysis. Receiver operating characteristic curve (ROC) analysis was used to evaluate the clinical value of hub genes. Gene set enrichment analysis (GSEA) was used to explore the biological changes related to hub genes, and the expression of hub genes was verified based on myocardial infarction dataset GSE123342.
Myocardial infarction was accompanied by an immune inflammatory response. Six novel hub genes were identified (CD163, RNASE2, HP, FAM20A, MCEMP1, and FAM198B). ROC analysis showed that the expression of these hub genes had good diagnostic for myocardial infarction. The expression of these genes also decreased significantly during recovery from infarction during recovering from myocardial infarction. GSEA results suggested that most of these hub genes were related to glucose and lipid metabolism, reactive oxygen species, immune inflammation and so on.
Based on the analysis of PBMCs, this study find that CD163, RNASE2, HP, FAM20A, MCEMP1 and FAM198B genes are associated with myocardial infarction, which may provide new insights for the early diagnosis of myocardial infarction and the monitoring, evaluation and management of infarction recovery.
[1] |
ZHAO D, LIU J, WANG M, et al. Epidemiology of cardiovascular disease in China: current features and implications[J]. Nat Rev Cardiol, 2019, 16(4): 203-212. doi: 10.1038/s41569-018-0119-4
|
[2] |
商广芸, 高燕飞, 曹洪波, 等. 急性心肌梗死的危险因素分析[J]. 实用临床医药杂志, 2020, 24(12): 48-50. https://www.cnki.com.cn/Article/CJFDTOTAL-XYZL202012015.htm
|
[3] |
WEIL B R, NEELAMEGHAM S. Selectins and immune cells in acute myocardial infarction and post-infarction ventricular remodeling: pathophysiology and novel treatments[J]. Front Immunol, 2019, 10: 300. doi: 10.3389/fimmu.2019.00300
|
[4] |
DE WINTER R J, KOSTER R W, STURK A, et al. Value of myoglobin, troponin T, and CK-MBmass in ruling out an acute myocardial infarction in the emergency room[J]. Circulation, 1995, 92(12): 3401-3407. doi: 10.1161/01.CIR.92.12.3401
|
[5] |
DE LEMOS J A, DRAZNER M H, OMLAND T, et al. Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population[J]. JAMA, 2010, 304(22): 2503-2512. doi: 10.1001/jama.2010.1768
|
[6] |
GE Y, WANG T J. Identifying novel biomarkers for cardiovascular disease risk prediction[J]. J Intern Med, 2012, 272(5): 430-439. doi: 10.1111/j.1365-2796.2012.02589.x
|
[7] |
WANG Y, ZHANG X Y, DUAN M, et al. Identification of potential biomarkers associated with acute myocardial infarction by weighted gene coexpression network analysis[J]. Oxid Med Cell Longev, 2021, 2021: 5553811.
|
[8] |
SEN P, KEMPPAINEN E, OREŠIC M. Perspectives on systems modeling of human peripheral blood mononuclear cells[J]. Front Mol Biosci, 2017, 4: 96.
|
[9] |
BARRETT T, WILHITE S E, LEDOUX P, et al. NCBI GEO: archive for functional genomics data sets: update[J]. Nucleic Acids Res, 2013, 41(Database issue): D991-D995.
|
[10] |
MACIEJAK A, KILISZEK M, MICHALAK M, et al. Gene expression profiling reveals potential prognostic biomarkers associated with the progression of heart failure[J]. Genome Med, 2015, 7(1): 26. doi: 10.1186/s13073-015-0149-z
|
[11] |
LANGFELDER P, HORVATH S. WGCNA: an R package for weighted correlation network analysis[J]. BMC Bioinformatics, 2008, 9: 559. doi: 10.1186/1471-2105-9-559
|
[12] |
DAS S, MEHER P K, RAI A, et al. Statistical approaches for gene selection, hub gene identification and module interaction in gene co-expression network analysis: an application to aluminum stress in soybean (glycine max l. )[J]. PLoS One, 2017, 12(1): e0169605. doi: 10.1371/journal.pone.0169605
|
[13] |
朱宝华, 孙岩. 冠状动脉疾病差异基因富集和加权基因共表达网络分析[J]. 实用临床医药杂志, 2021, 25(17): 15-21. doi: 10.7619/jcmp.20212119
|
[14] |
YU G C, WANG L G, HAN Y Y, et al. clusterProfiler: an R package for comparing biological themes among gene clusters[J]. OMICS, 2012, 16(5): 284-287. doi: 10.1089/omi.2011.0118
|
[15] |
RITCHIE M E, PHIPSON B, WU D, et al. Limma Powers differential expression analyses for RNA-sequencing and microarray studies[J]. Nucleic Acids Res, 2015, 43(7): e47. doi: 10.1093/nar/gkv007
|
[16] |
KEENAN A B, TORRE D, LACHMANN A, et al. ChEA3: transcription factor enrichment analysis by orthogonal omics integration[J]. Nucleic Acids Res, 2019, 47(W1): W212-W224. doi: 10.1093/nar/gkz446
|
[17] |
FU Z J, XU Y Q, CHEN Y, et al. Construction of miRNA-mRNA-TF regulatory network for diagnosis of gastric cancer[J]. Biomed Res Int, 2021, 2021: 9121478.
|
[18] |
SZKLARCZYK D, GABLE A L, NASTOU K C, et al. The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets[J]. Nucleic Acids Res, 2021, 49(D1): D605-D612. doi: 10.1093/nar/gkaa1074
|
[19] |
SHANNON P, MARKIEL A, OZIER O, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks[J]. Genome Res, 2003, 13(11): 2498-2504. doi: 10.1101/gr.1239303
|
[20] |
MCELIGOT A J, POYNOR V, SHARMA R, et al. Logistic LASSO regression for dietary intakes and breast cancer[J]. Nutrients, 2020, 12(9): 2652. doi: 10.3390/nu12092652
|
[21] |
ENGEBRETSEN S, BOHLIN J. Statistical predictions with glmnet[J]. Clin Epigenetics, 2019, 11(1): 123. doi: 10.1186/s13148-019-0730-1
|
[22] |
ROBIN X, TURCK N, HAINARD A, et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves[J]. BMC Bioinformatics, 2011, 12: 77. doi: 10.1186/1471-2105-12-77
|
[23] |
SUBRAMANIAN A, TAMAYO P, MOOTHA V K, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles[J]. Proc Natl Acad Sci USA, 2005, 102(43): 15545-15550. doi: 10.1073/pnas.0506580102
|
[24] |
GUO L, AKAHORI H, HARARI E, et al. CD163+ macrophages promote angiogenesis and vascular permeability accompanied by inflammation in atherosclerosis[J]. J Clin Invest, 2018, 128(3): 1106-1124. doi: 10.1172/JCI93025
|
[25] |
WU T F, CHEN Y X, YANG L Y, et al. Ribonuclease A family member 2 promotes the malignant progression of glioma through the PI3K/Akt signaling pathway[J]. Front Oncol, 2022, 12: 921083. doi: 10.3389/fonc.2022.921083
|
[26] |
LI L L, SAIYIN W, ZHANG H, et al. FAM20A is essential for amelogenesis, but is dispensable for dentinogenesis[J]. J Mol Histol, 2019, 50(6): 581-591. doi: 10.1007/s10735-019-09851-x
|
[27] |
RAMAN K, O'DONNELL M J, CZLONKOWSKA A, et al. Peripheral blood MCEMP1 gene expression as a biomarker for stroke prognosis[J]. Stroke, 2016, 47(3): 652-658. doi: 10.1161/STROKEAHA.115.011854
|
[28] |
QIU L, LIU X. Identification of key genes involved in myocardial infarction[J]. Eur J Med Res, 2019, 24(1): 22. doi: 10.1186/s40001-019-0381-x
|
[29] |
KILISZEK M, BURZYNSKA B, MICHALAK M, et al. Altered gene expression pattern in peripheral blood mononuclear cells in patients with acute myocardial infarction[J]. PLoS One, 2012, 7(11): e50054. doi: 10.1371/journal.pone.0050054
|
[30] |
GURUNG R L, YIAMUNAA M, LIU S, et al. Association of haptoglobin phenotype with incident acute myocardial infarction in Chinese patients with type 2 diabetes[J]. Cardiovasc Diabetol, 2019, 18(1): 65. doi: 10.1186/s12933-019-0867-4
|
[31] |
BLUM S, ASAF R, GUETTA J, et al. Haptoglobin genotype determines myocardial infarct size in diabetic mice[J]. J Am Coll Cardiol, 2007, 49(1): 82-87. doi: 10.1016/j.jacc.2006.08.044
|
[32] |
HSU C Y, CHANG G C, CHEN Y J, et al. FAM198B is associated with prolonged survival and inhibits metastasis in lung adenocarcinoma via blockage of ERK-mediated MMP-1 expression[J]. Clin Cancer Res, 2018, 24(4): 916-926. doi: 10.1158/1078-0432.CCR-17-1347
|