Correlation between iron death⁃related gene expression level and myocardial dysfunction and prognosis in sepsis
Received date: 2024-11-07
Online published: 2025-03-31
目的 探讨铁死亡相关基因表达水平与脓毒症患者心肌功能障碍及预后的相关性。 方法 纳入2023年5月至2024年8月本院收治的85例脓毒症患者,根据心肌功能障碍发生情况分为障碍组(39例)和非障碍组(46例)。收集患者年龄、原发疾病等临床资料;采集肺组织标本,检测细胞色素p450氧化还原酶(POR)、溶质载体家族7成员5(SLC7A5)和信号转导和转录激活因子3(STAT3)铁死亡相关基因的mRNA表达水平。通过多因素logistic回归分析铁死亡相关基因表达水平与脓毒症心肌功能障碍(SIMD)的相关性;绘制Kaplan-Meier生存曲线分析铁死亡相关基因表达水平与脓毒症患者预后的相关性。 结果 障碍组脓毒症患者男性占比、年龄和POR、SLC7A5及STAT3表达水平均高于非障碍组(P < 0.05)。在排除性别、年龄等混杂因素的干扰后,POR、SLC7A5及STAT3表达水平是SIMD的独立影响因素(P < 0.05)。绘制ROC曲线显示,POR表达水平预测SIMD的AUC为0.677(95%CI:0.561 ~ 0.792),敏感度、特异度分别为87.20%、54.30%;SLC7A5表达水平预测SIMD的AUC为0.844(95%CI:0.749 ~ 0.939),敏感度、特异度分别为74.40%、93.50%;STAT3表达水平预测SIMD的AUC为0.690(95%CI:0.570 ~ 0.809),敏感度、特异度分别为69.20%、71.70%。随访期间,85例脓毒症患者中,有69例(81.18%)存活,16例(18.82%)死亡;绘制Kaplan-Meier生存曲线显示,POR、SLC7A5表达水平与脓毒症患者28 d生存率相关(χ 2 = 6.048/10.143,P < 0.05),STAT3表达水平与脓毒症患者28 d生存率无显著关联(χ 2 = 2.149,P > 0.05)。 结论 POR、SLC7A5及STAT3表达水平与SIMD密切相关,其中POR、SLC7A5表达水平与脓毒症患者预后显著相关。
段彤 , 吴奇 , 刘惠 . 铁死亡相关基因表达水平与脓毒症心肌功能障碍及预后的相关性[J]. 实用医学杂志, 2025 , 41(6) : 846 -851 . DOI: 10.3969/j.issn.1006-5725.2025.06.011
Objective To examine the correlation between ferroptosis-related gene expression levels and myocardial dysfunction as well as prognosis in sepsis patients. Methods Eighty-five sepsis patients admitted to our hospital from May 2023 to August 2024 were categorized into two groups based on the presence of myocardial dysfunction: the impaired group (n = 39) and the non-impaired group (n = 46). The mRNA expression levels of cytochrome P450 oxidoreductase (POR), solute carrier family 7 member 5 (SLC7A5), and signal transducer and activator of transcription 3 (STAT3) were measured. Multivariate logistic regression analysis was conducted to examine the correlation between the expression levels of iron death-related genes and sepsis-induced myocardial dysfunction (SIMD). Kaplan-Meier survival curves were plotted to evaluate the relationship between the expression levels of iron death-related genes and the prognosis of sepsis patients. Results In patients with sepsis, the disorder group exhibited higher male proportions, age, and expression levels of POR, SLC7A5, and STAT3 compared to the non-disorder group (P < 0.05). After adjusting for potential confounders such as gender and age, the expression levels of POR, SLC7A5, and STAT3 remained independent predictors of SIMD (P < 0.05). The ROC curve analysis revealed that the AUC for POR expression in predicting SIMD was 0.677 (95%CI: 0.561 ~ 0.792), with a sensitivity of 87.20% and specificity of 54.30%. For SLC7A5, the AUC was 0.844 (95%CI: 0.749 ~ 0.939), with a sensitivity of 74.40% and specificity of 93.50%. STAT3 had an AUC of 0.690 (95%CI: 0.570 ~ 0.809), with a sensitivity of 69.20% and specificity of 71.70%. During the follow-up period, 69 patients (81.18%) survived, while 16 (18.82%) did not. Kaplan-Meier survival analysis indicated that POR and SLC7A5 expression levels were significantly associated with the 28-day survival rate of septic patients (χ2 = 6.048/10.143, P < 0.05), whereas STAT3 expression showed no significant correlation (χ2 = 2.149, P > 0.05). Conclusion The expression levels of POR, SLC7A5 and STAT3 are closely related to SIMD, and the expression levels of POR and SLC7A5 are significantly related to the prognosis of sepsis patients.
Key words: iron death; sepsis; myocardial dysfunction; prognosis; correlation
| 1 | GAUER R, FORBES D, BOYER N. Sepsis: Diagnosis and Management[J]. Am Fam Physician, 2020,101(7):409-418. |
| 2 | RUDD K E, JOHNSON S C, AGESA K M, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: Analysis for the Global Burden of Disease Study[J]. Lancet, 2020,395(10219):200-211. doi:10.1016/s0140-6736(19)32989-7 |
| 3 | 刘敏,陈喜云,吕建磊,等. ALKBH5通过TRAF1/NF-κB通路减轻脓毒症心肌损伤的机制[J]. 实用医学杂志,2024,40(17):2381-2389. |
| 4 | CHEN M, KONG C, ZHENG Z, et al. Identification of Biomarkers Associated with Septic Cardiomyopathy Based on Bioinformatics Analyses[J]. J Comput Biol, 2020,27(1):69-80. doi:10.1089/cmb.2019.0181 |
| 5 | YAN H F, ZOU T, TUO Q Z, et al. Ferroptosis: Mechanisms and links with diseases[J]. Signal Transduct Target Ther, 2021,6(1):49. doi:10.1038/s41392-020-00428-9 |
| 6 | WANG C, YUAN W, HU A, et al. Dexmedetomidine alleviated sepsis?induced myocardial ferroptosis and septic heart injury[J]. Mol Med Rep, 2020,22(1):175-184. doi:10.3892/mmr.2020.11114 |
| 7 | LI N, WANG W, ZHOU H, et al. Ferritinophagy-mediated ferroptosis is involved in sepsis-induced cardiac injury[J]. Free Radic Biol Med, 2020,160(1):303-318. doi:10.1016/j.freeradbiomed.2020.08.009 |
| 8 | SONG J, REN K, ZHANG D, et al. A novel signature combing cuproptosis- and ferroptosis-related genes in sepsis-induced cardiomyopathy[J]. Front Genet, 2023,14(1):1170737. doi:10.3389/fgene.2023.1170737 |
| 9 | WANG P F, NEINER A, KHARASCH E D. Stereoselective Bupropion Hydroxylation by Cytochrome P450 CYP2B6 and Cytochrome P450 Oxidoreductase Genetic Variants[J]. Drug Metab Dispos, 2020,48(6):438-445. doi:10.1124/dmd.119.090407 |
| 10 | SINGER M, DEUTSCHMAN C S, SEYMOUR C W, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)[J]. JAMA, 2016,315(8):801-810. doi:10.1001/jama.2016.0287 |
| 11 | BEESLEY S J, WEBER G, SARGE T, et al. Septic Cardiomyopathy[J]. Crit Care Med, 2018,46(4):625-634. doi:10.1097/ccm.0000000000002851 |
| 12 | PARKER M M, SHELHAMER J H, BACHARACH S L, et al. Profound but reversible myocardial depression in patients with septic shock[J]. Ann Intern Med, 1984,100(4):483-490. doi:10.7326/0003-4819-100-4-483 |
| 13 | L'HEUREUX M, STERNBERG M, BRATH L, et al. Sepsis-Induced Cardiomyopathy: A Comprehensive Review[J]. Curr Cardiol Rep, 2020,22(5):35. doi:10.1007/s11886-020-01277-2 |
| 14 | 卢天龙,杨启英,杨世闻,等. 精氨酸甲基转移酶1调控铁死亡在肺癌细胞恶性生物学中的分子机制[J]. 实用医学杂志, 2023, 39(9):1098-1104. |
| 15 | FANG X, WANG H, HAN D, et al. Ferroptosis as a target for protection against cardiomyopathy[J]. Proc Natl Acad Sci U S A, 2019,116(7):2672-2680. doi:10.1073/pnas.1821022116 |
| 16 | YOSHIDA M, MINAGAWA S, ARAYA J, et al. Involvement of cigarette smoke-induced epithelial cell ferroptosis in COPD pathogenesis[J]. Nat Commun, 2019,10(1):3145. doi:10.1038/s41467-019-10991-7 |
| 17 | ZHU L, CHEN D, ZHU Y, et al. GPX4-Regulated Ferroptosis Mediates S100-Induced Experimental Autoimmune Hepatitis Associated with the Nrf2/HO-1 Signaling Pathway[J]. Oxid Med Cell Longev, 2021,2021(1):6551069. doi:10.1155/2021/6551069 |
| 18 | LIU Y, TAN S, WU Y, et al. The Emerging Role of Ferroptosis in Sepsis[J]. DNA Cell Biol, 2022,41(4):368-380. doi:10.1089/dna.2021.1072 |
| 19 | SUGISHIMA M, SATO H, WADA K, et al. Crystal structure of a NADPH-cytochrome P450 oxidoreductase (CYPOR) and heme oxygenase 1 fusion protein implies a conformational change in CYPOR upon NADPH/NADP(+) binding[J]. FEBS Lett, 2019,593(8):868-875. doi:10.1002/1873-3468.13360 |
| 20 | LIU J, KANG R, TANG D. Signaling pathways and defense mechanisms of ferroptosis[J]. FEBS J, 2022,289(22):7038-7050. doi:10.1111/febs.16059 |
| 21 | LI J, ZHOU L, LI Z, et al. Identification of Crucial Genes and Infiltrating Immune Cells Underlying Sepsis-Induced Cardiomyopathy via Weighted Gene Co-Expression Network Analysis[J]. Front Genet, 2021,12(1):812509. doi:10.3389/fgene.2021.812509 |
| 22 | 廖景龙, 罗涵深, 霍博. 皮肤黑色素瘤预后模型的构建:基于TCGA数据库的铁死亡相关基因[J]. 皮肤性病诊疗学杂志,2023,30(4):307-313. |
| 23 | CHEN Z, CAI H, YE W, et al. TP63 transcriptionally regulates SLC7A5 to suppress ferroptosis in head and neck squamous cell carcinoma[J]. Front Immunol, 2024,15(1):1445472. doi:10.3389/fimmu.2024.1445472 |
| 24 | ZHENG H, ZHANG X, LI C, et al. BCAA mediated microbiota-liver-heart crosstalk regulates diabetic cardiomyopathy via FGF21[J]. Microbiome, 2024,12(1):157. doi:10.1186/s40168-024-01872-3 |
| 25 | WANG Y, MOU Y K, LIU W C, et al. Machine learning developed a macrophage signature for predicting prognosis, immune infiltration and immunotherapy features in head and neck squamous cell carcinoma[J]. Sci Rep, 2024,14(1):19538. doi:10.1038/s41598-024-70430-6 |
| 26 | MAO J, MA X. Bioinformatics Identification of Ferroptosis-Associated Biomarkers and Therapeutic Compounds in Psoriasis[J]. J Oncol, 2022,2022(1):3818216. doi:10.1155/2022/3818216 |
| 27 | LAKSHMANACHETTY S, BALAIYA V, HIGH W A, et al. Loss of TP63 Promotes the Metastasis of Head and Neck Squamous Cell Carcinoma by Activating MAPK and STAT3 Signaling[J]. Mol Cancer Res, 2019,17(6):1279-1293. doi:10.1158/1541-7786.mcr-18-1355 |
| 28 | LEI W, LIU D, SUN M, et al. Targeting STAT3: A crucial modulator of sepsis[J]. J Cell Physiol, 2021,236(11):7814-7831. doi:10.1002/jcp.30394 |
| 29 | 孙永, 史兆博, 刘美香,等. 山药多糖对脓毒症大鼠心肌损伤及JAK2/STAT3信号通路的影响[J]. 中国动脉硬化杂志,2022,30(8):669-675. |
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