种植体周围炎中铁死亡的生物信息学分析与实验验证

doi:10.13591/j.cnki.kqyx.2024.07.008

Abstract

Abstract:

Objective To investigate the key genes associated with ferroptosis in peri-implantitis and explore the potential mechanisms regulating peri-implantitis. Methods Several datasets were obtained from the GEO database. Differential expressed genes were screened, and GO and KEGG analyses were performed. A PPI network was constructed using the STRING website. Key genes were validated using a test set, and the diagnostic value of key genes was determined. The content and proportion of 22 immune cells in peri-implantitis tissues were obtained through immune infiltration analysis. Key genes were validated by qRT-PCR and Western Blot(WB). Results There were 1 138 differential genes between peri-implantitis tissues and normal gingival tissues, of which 29 were related to ferroptosis. The gene expression in peri-implantitis tissues mainly involved processes such as immune response activation. Five key genes in the ferroptosis-related differential genes, namely SOX2, GJA1, IL1B, GPX2 and CHAC1, were differentially expressed in peri-implantitis tissues and had high diagnostic value. Immune infiltration analysis showed significant changes in immune cells such as memory B cells and plasma cells in peri-implantitis tissues. qRT-PCR and WB confirmed significant differential expression of mRNA and the protein transcribed by key genes. Conclusion Differential genes between peri-implantitis and ferroptosis are screened using bioinformatics analysis and biological validation, providing new insights into the study on peri-implantitis.

Key words: GEO database, bioinformatics, peri-implantitis, ferroptosis, differential expressed genes

CLC Number:

R318.04

ZHANG Zhewei, WANG Jiaohong, WU Wei, DONG Shuo, LI Guoqing, TANG Chunbo. Bioinformatics analysis and experimental validation of ferroptosis in peri-implantitis[J]. Stomatology, 2024, 44(7): 527-535.

Figures/Tables 14

Tab.1

Fig.1

Fig.2

Fig.3

Tab.2

Tab.3

Fig.4

Fig.5

Fig.6

Fig.7

Fig.8

Fig.9

Fig.10

Fig.11

References 20

[1]	Berglundh T, Armitage G, Araujo MG, et al. Peri-implant diseases and conditions: Consensus report of workgroup 4 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions[J]. J Clin Periodontol, 2018, 45(Suppl 20): S286-S291.
[2]	Pan SF, Li Y, He HK, et al. Identification of ferroptosis, necroptosis, and pyroptosis-associated genes in periodontitis-affected human periodontal tissue using integrated bioinformatic analysis[J]. Front Pharmacol, 2023, 13: 1098851.
[3]	Wu XG, Li Y, Zhang SC, et al. Ferroptosis as a novel therapeutic target for cardiovascular disease[J]. Theranostics, 2021, 11(7): 3052-3059. doi: 10.7150/thno.54113 pmid: 33537073
[4]	Mumford DB. ROC analysis[J]. Br J Psychiatry, 1990, 157(2): 301.
[5]	Davis S, Meltzer PS. GEOquery: A bridge between the Gene Expression Omnibus(GEO)and BioConductor[J]. Bioinformatics, 2007, 23(14): 1846-1847. doi: 10.1093/bioinformatics/btm254 pmid: 17496320
[6]	Gustavsson EK, Zhang D, Reynolds RH, et al. Ggtranscript: An R package for the visualization and interpretation of transcript isoforms using ggplot2[J]. Bioinformatics, 2022, 38(15): 3844-3846. doi: 10.1093/bioinformatics/btac409 pmid: 35751589
[7]	Consortium TGO. The Gene Ontology Resource: 20 years and still GOing strong[J]. Nucleic Acids Res, 2019, 47(D1): D330-D338. doi: 10.1093/nar/gky1055
[8]	Hashimoto K, Goto S, Kawano S, et al. KEGG as a glycome informatics resource[J]. Glycobiology, 2006, 16(5): 63R-70R. pmid: 16014746
[9]	Zhou N, Yuan XQ, Du QS, et al. FerrDb V2: Update of the manually curated database of ferroptosis regulators and ferroptosis-disease associations[J]. Nucleic Acids Res, 2023, 51(D1): D571-D582.
[10]	Doncheva NT, Morris JH, Gorodkin J, et al. Cytoscape StringApp: Network analysis and visualization of proteomics data[J]. J Proteome Res, 2019, 18(2): 623-632. doi: 10.1021/acs.jproteome.8b00702 pmid: 30450911
[11]	Ritchie ME, 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.
[12]	Jiang XJ, Stockwell BR, Conrad M. Ferroptosis: Mechanisms, biology and role in disease[J]. Nat Rev Mol Cell Biol, 2021, 22(4): 266-282.
[13]	Che CY, Liu J, Yang JJ, et al. Osteopontin is essential for IL-1β production and apoptosis in peri-implantitis[J]. Clin Implant Dent Relat Res, 2018, 20(3): 384-392.
[14]	Wang Y, Niu HC, Li LY, et al. Anti-CHAC1 exosomes for nose-to-brain delivery of miR-760-3p in cerebral ischemia/reperfusion injury mice inhibiting neuron ferroptosis[J]. J Nanobiotechnology, 2023, 21(1): 109.
[15]	Xiao RX, Wang SS, Guo J, et al. Ferroptosis-related gene NOX4, CHAC1 and HIF1A are valid biomarkers for stomach adenocarcinoma[J]. J Cell Mol Med, 2022, 26(4): 1183-1193. doi: 10.1111/jcmm.17171 pmid: 35023280
[16]	Kajiwara Y, Wang EM, Wang MH, et al. GJA1(connexin43)is a key regulator of Alzheimer’s disease pathogenesis[J]. Acta Neuropathol Commun, 2018, 6(1): 144.
[17]	Raza IGA, Clarke AJ. B cell metabolism and autophagy in autoimmunity[J]. Front Immunol, 2021, 12: 681105.
[18]	Eibel H, Kraus H, Sic H, et al. B cell biology: An overview[J]. Curr Allergy Asthma Rep, 2014, 14(5): 434.
[19]	Pahl JHW, Koch J, Götz JJ, et al. CD16A activation of NK cells promotes NK cell proliferation and memory-like cytotoxicity against cancer cells[J]. Cancer Immunol Res, 2018, 6(5): 517-527. doi: 10.1158/2326-6066.CIR-17-0550 pmid: 29514797
[20]	Yao F, Deng YL, Zhao Y, et al. A targetable LIFR-NF-κB-LCN2 axis controls liver tumorigenesis and vulnerability to ferroptosis[J]. Nat Commun, 2021, 12(1): 7333. doi: 10.1038/s41467-021-27452-9 pmid: 34921145

基因名称	引物序列(5'—3')
SOX2-F	GACAGTTACGCGCACATGAA
SOX2-R	GTTCATGTAGGTCTGCGAGC
GJA1-L	CTCGCCTATGTCTCCTCCTG
GJA1-R	CCCAGTTTTGCTCACTTGCT
GPX2-L	ATGTGAGGTGAATGGGCAGA
GPX2-R	ATGATGAGCTTGGGATCGGT
CHAC1-L	GATCATGAGGGCTGCACTTG
CHAC1-R	CCACAGAGCTGCATGAAGTC
IL1B-L	CGAATCTCCGACCACCACTA
IL1B-R	AGCCTCGTTATCCCATGTG

通路	基因数目	富集评分	校正后的归一化的富集评分值	P
造血细胞谱系	91	0.66	2.34	1.03×10^-10
细胞因子与细胞因子受体相互作用	267	0.54	2.19	1.00×10^-10
NF-κB信号通路	96	0.62	2.24	2.61×10^-9
趋化因子信号通路	179	0.52	2.04	7.13×10^-9
类风湿性关节炎	83	0.63	2.22	1.96×10^-8

通路描述	基因数目	富集评分	校正后的归一化的富集评分值	P
B细胞增殖	96	0.72	2.59	1.00×10^-10
B细胞增殖调节	63	0.73	2.45	1.00×10^-10
免疫应答调节细胞表面受体信号通路	291	0.59	2.43	1.00×10^-10
B细胞受体信号通路	64	0.72	2.40	1.00×10^-10
适应性免疫应答	450	0.56	2.40	1.00×10^-10

Bioinformatics analysis and experimental validation of ferroptosis in peri-implantitis

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 14

References 20

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	CHEN Yiren, ZHAO Zhenyuan, ZHENG Yangyu, ZHANG Wei, SONG Xiaomeng. FBXW7 promotes ferroptosis in head and neck squamous cell carcinoma cells through inhibiting c-Myc/SOX2/SLC7A11 [J]. Stomatology, 2024, 44(6): 426-432.
[2]	WANG Yiwei, SHU Rong, XIE Yufeng, QIAN Jielei, LIN Zhikai. A short-time non-randomized controlled clinical study on adjunctive photodynamic therapy in the treatment of peri-implantitis [J]. Stomatology, 2024, 44(6): 414-420.
[3]	ZHANG Zhihao, YANG Yi, WANG Yueqiu, SUN Siyi, CHEN Hong, SHU Fei, LIU Mei. Immune-related genes shared between Crohn's disease and periodontitis and their potential as diagnostic biomarkers [J]. Stomatology, 2024, 44(3): 184-191.
[4]	TANG Jinxin, TANG Chunbo, SONG Xin, RUI Na, XUE Chang'ao. Establishment of risk prediction model for peri-implantitis after dental implants in patients with periodontitis [J]. Stomatology, 2023, 43(8): 706-710.
[5]	DAI Yuwei, LI Jie, SUN Yuanyuan, WU Yiqun, MENG Jian. Research progress and application of rodents model construction of peri-implantitis [J]. Stomatology, 2023, 43(2): 182-187.
[6]	ZHOU Yi,CHEN Jiajie. Re-osseointegration of peri-implantitis affected and failed implants [J]. Stomatology, 2023, 43(1): 35-38.
[7]	ZHANG Cheng, LU Di, LIU Zongxiang, WANG Penglai. Advances of research on melatonin in oral implantation therapy [J]. Stomatology, 2022, 42(2): 184-187.
[8]	. Clinical application of smooth-collared implant [J]. , 2021, 41(8): 746-750.
[9]	. [J]. , 2021, 41(10): 865-871.
[10]	. Exploration of differential expression genes between ameloblastoma and odontogenic keratocyst based on GEO database [J]. , 2020, 40(11): 1009-1014.
[11]	. Flap surgery is required when “saucer-like” marginal bone loss amounted to 3 mm below implant shoulder after 1-year loading [J]. , 2019, 39(2): 161-163.
[12]	. Neither open flap debridement nor bone grafting when “saucer-like” marginal bone loss amounts to 3 mm below the implant shoulder after 1-year functional loading [J]. , 2019, 39(2): 164-166.
[13]	. Research progress of animal models of peri-implantitis [J]. , 2018, 38(8): 747-751.
[14]	. Review on photodynamic therapy in treatment of peri-implantitis [J]. , 2018, 38(6): 569-572.
[15]	. Effect of probiotics on common oral diseases [J]. , 2018, 38(2): 185-188.