目的：探讨肝母细胞瘤（hepatoblastoma,HB）患者血清活性氧调节剂1（ROS modulator 1,ROMO1）、活性氧（reactive oxygen species,ROS）、C反应蛋白（C-reactive protein,CRP）的水平及其与临床病理特征的相关性。方法：选取济南市人民医院与济南市第二妇幼保健院2019年9月至2024年6月收治的74例HB患儿为研究对象（肝母细胞瘤组）,另选取同期入院检查的70例健康儿童作为对照（健康组）。检测并比较两组血清ROMO1、ROS、CRP水平;进一步分析不同临床病理特征下HB患者血清ROMO1、ROS、CRP水平变化;采用Spearman分析血清ROMO1、ROS、CRP水平与病情严重程度之间的相关性。绘制受试者工作特征曲线（receiver operator characteristic curve,ROC）曲线分析ROMO1、ROS、CRP水平对HB的诊断效能。结果：HB患者血清ROMO1、ROS、CRP水平均显著高于健康组[（131.74±9.83）pg/mL vs（92.63±7.71）pg/mL、（286.15±25.47）nmol/mL vs （236.82±15.69）nmol/mL、（6.83±2.03）mg/L vs（4.89±1.15）mg/L],差异均有统计学意义;不同肿瘤直径、病理分型HB患者血清ROMO1、ROS、CRP水平差异无统计学意义;不同甲胎蛋白、TNM分期、分化程度及肿瘤侵袭或转移患者血清ROMO1、ROS、CRP水平具有统计学意义;Spearman相关性分析显示,血清ROMO1、ROS、CRP水平与TNM分期均呈显著正相关（r=0.8757、0.8392、0.8109,P<0.001）。ROC曲线分析结果显示,血清ROMO1、ROS、CRP单一检测及联合诊断HB均具有一定的诊断价值,三项联合诊断效能[AUC=0.992（0.863~0.981）],P<0.05）明显高于单一诊断。结论：HB患者血清ROMO1、ROS、CRP水平升高与病情严重程度呈正相关,且对HB具有一定的诊断价值,可能是监测HB严重程度和治疗效果的重要参数。
Abstract
Objective To explore the serum levels of ROS modulator 1 (ROMO1), reactive oxygen species (ROS) and C-reactive protein (CRP) in patients with hepatoblastoma (HB) and their correlation with clinicopathological features. Methods Seventy-four HB children admitted to Jinan People's Hospital and Jinan Second Maternal and Child Health Hospital from September 2019 to June 2024 were selected as the study objects and included in the hepatoblastoma group, and 70 healthy patients admitted to the hospital for examination during the same period were selected as the healthy group. The serum levels of ROMO1, ROS and CRP were detected and compared between the two groups. The serum levels of ROMO1, ROS and CRP in HB patients were further analyzed under different clinicopathological characteristics. The correlation between serum levels of ROMO1, ROS, CRP and the severity of the disease was analyzed by Spearman. ROC curve analysis was performed to evaluate the diagnostic efficacy of ROMO1, ROS, and CRP levels in HB. Results The serum ROMO1, ROS and CRP levels in HB patients were significantly higher than those in the healthy group [(131.74±9.83 vs 92.63±7.71) pg/mL, (286.15±25.47 vs 236.82±15.69) nmol/mL, (6.83±2.03 vs 4.89±1.15) mg/L], the difference was statistically significant; There was no significant difference in serum levels of ROMO1, ROS and CRP among HB patients with different tumor diameter and pathological type. and the differences in serum ROMO1, ROS, and CRP levels among patients with different alpha-fetoprotein, TNM staging, degree of differentiation, and tumor invasion or metastasis were statistically significant; Spearman correlation analysis showed that serum ROMO1, ROS, CRP levels were significantly positively correlated with TNM stage (r=0.8757, 0.8392, 0.8109, P<0.001). The ROC curve analysis results showed that the single detection and combined diagnosis of serum ROMO1, ROS, CRP all have certain diagnostic value for HB, and the combined diagnostic efficiency of the three items [AUC: 0.992 (0.863-0.981), P<0.05] is significantly higher than that of single diagnosis. Conclusions The elevated levels of serum ROMO1, ROS, and CRP in patients with HB are positively correlated with the severity of the disease and have certain diagnostic value for HB. They may be important parameters for monitoring the severity of HB and treatment efficacy.
关键词
肝母细胞瘤 /
活性氧调节剂1 /
活性氧 /
C反应蛋白
Key words
hepatoblastoma /
reactive oxygen species modulator 1 /
reactive oxygen species /
C-reactive protein
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参考文献
[1] ZHANG Y, SOLINAS A, CAIRO S, et al.Molecular Mechanisms of Hepatoblastoma[J]. Semin Liver Dis, 2021, 41(1): 28-41.
[2] WU Z, XIA F, WANG W, et al.Worldwide burden of liver cancer across childhood and adolescence, 2000-2021: a systematic analysis of the Global Burden of Disease Study 2021[J]. EClinicalMedicine, 2024, 75: 102765.
[3] LIM I, BONDOC A J, GELLER J I, et al.Hepatoblastoma-The Evolution of Biology, Surgery, and Transplantation[J]. Children (Basel), 2018, 6(1): 1.
[4] HAFBERG E, BORINSTEIN S C, ALEXOPOULOS S P.Contemporary management of hepatoblastoma[J]. Curr Opin Organ Transplant, 2019, 24(2): 113-117.
[5] ZHENG C, YE S, LIU W, et al.Prognostic value of systemic inflammation response index in hepatoblastoma patients receiving preoperative neoadjuvant chemotherapy[J]. Front Oncol, 2023, 13: 1276175.
[6] FUCHS J, RABAUX-EYGASIER L, RUPING F, et al.Reappraisal of liver resection as an alternative to transplantation in locally advanced hepatoblastoma: A systematic review and analysis of pooled individual patient data[J]. Pediatr Blood Cancer, 2024, 71(12): e31339.
[7] DEMBOWSKA-BAGINSKA B, WIECKOWSKA J, BROZYNA A, et al.Health Status in Long-Term Survivors of Hepatoblastoma[J]. Cancers (Basel), 2019, 11(11): 1777.
[8] JAMAR N H, KRITSILIGKOU P, GRANT C M.The non-stop decay mRNA surveillance pathway is required for oxidative stress tolerance[J]. Nucleic Acids Res, 2017, 45(11): 6881-6893.
[9] WANG L, LIU X, LIU Z, et al.Network models of prostate cancer immune microenvironments identify ROMO1 as heterogeneity and prognostic marker[J]. Sci Rep, 2022, 12(1): 192.
[10] AMINI M A, TALEBI S S, KARIMI J.Reactive Oxygen Species Modulator 1 (ROMO1), a New Potential Target for Cancer Diagnosis and Treatment[J]. Chonnam Med J, 2019, 55(3): 136-143.
[11] KINOSHITA T, GOTO T.Links between Inflammation and Postoperative Cancer Recurrence[J]. J Clin Med, 2021, 10(2): 228.
[12] HART P C, RAJAB I M, ALEBRAHEEM M, et al.C-Reactive Protein and Cancer-Diagnostic and Therapeutic Insights[J]. Front Immunol, 2020, 11: 595835.
[13] RI M, TZORTZAKAKIS A, SOTIROVA I, et al.CRP as an early indicator for anastomotic leakage after esophagectomy for cancer: a single tertiary gastro-esophageal center study[J]. Langenbecks Arch Surg, 2023, 408(1): 436.
[14] 倪鑫. 儿童肝母细胞瘤诊疗规范(2019年版)[J]. 临床肝胆病杂志, 2019, 35(11): 2431-2434.
[15] MORIN C E, ARTUNDUAGA M, SCHOOLER G R, et al.Imaging for Staging of Pediatric Abdominal Tumors: An Update, From the AJR Special Series on Cancer Staging[J]. AJR Am J Roentgenol, 2021, 217(4): 786-799.
[16] REN H, ZHUO Z J, DUAN F, et al.ALKBH5 Gene Polymorphisms and Hepatoblastoma Susceptibility in Chinese Children[J]. J Oncol, 2021, 2021: 6658480.
[17] HOOKS K B, AUDOUX J, FAZLI H, et al.New insights into diagnosis and therapeutic options for proliferative hepatoblastoma[J]. Hepatology, 2018, 68(1): 89-102.
[18] CARRILLO-REIXACH J, TORRENS L, SIMON-COMA M, et al.Epigenetic footprint enables molecular risk stratification of hepatoblastoma with clinical implications[J]. J Hepatol, 2020, 73(2): 328-341.
[19] SUN R, LI S, ZHAO K, et al.Identification of Ten Core Hub Genes as Potential Biomarkers and Treatment Target for Hepatoblastoma[J]. Front Oncol, 2021, 11: 591507.
[20] LIU W, CHEN S, LIU B.Diagnostic and prognostic values of serum exosomal microRNA-21 in children with hepatoblastoma: a Chinese population-based study[J]. Pediatr Surg Int, 2016, 32(11): 1059-1065.
[21] ZHENG D, LIU J, PIAO H, et al.ROS-triggered endothelial cell death mechanisms: Focus on pyroptosis, parthanatos, and ferroptosis[J]. Front Immunol, 2022, 13: 1039241.
[22] CHEUNG E C, VOUSDEN K H.The role of ROS in tumour development and progression[J]. Nat Rev Cancer, 2022, 22(5): 280-297.
[23] KUO C L, PONNERI B A, LIN Y C, et al.Mitochondrial oxidative stress in the tumor microenvironment and cancer immunoescape: foe or friend?[J]. J Biomed Sci, 2022, 29(1): 74.
[24] JO M J, KIM B G, PARK S H, et al.Romo1 Inhibition Induces TRAIL-Mediated Apoptosis in Colorectal Cancer[J]. Cancers (Basel), 2020, 12(9): 2358.
[25] SUN G, CAO Y, QIAN C, et al.Romo1 is involved in the immune response of glioblastoma by regulating the function of macrophages[J]. Aging (Albany NY), 2020, 12(2): 1114-1127.
[26] YE L, MAO S, FANG S, et al.Increased Serum Romo1 Was Correlated with Lung Function, Inflammation, and Oxidative Stress in Chronic Obstructive Pulmonary Disease[J]. Inflammation, 2019, 42(5): 1555-1560.
[27] WANG M, CHEN S, HE X, et al.Targeting inflammation as cancer therapy[J]. J Hematol Oncol, 2024, 17(1): 13.
[28] IKWEGBUE P C, MASAMBA P, OYINLOYE B E, et al.Roles of Heat Shock Proteins in Apoptosis, Oxidative Stress, Human Inflammatory Diseases, and Cancer[J]. Pharmaceuticals (Basel), 2017, 11(1): 2.
[29] LV J, WU Y, LI W, et al.High Expression of ROMO1 Aggravates the Malignancy of Hepatoblastoma[J]. J Oncol, 2021, 2021: 2341719.
[30] SATO Y, KOKUBU A, FUKUSHIMA K, et al.Fluctuations in C-reactive protein in a hepatoblastoma patient with thrombocytosis[J]. Clin Pract, 2011, 1(3): e56.
基金
山东省济南市卫生健康委员会科技计划项目“ROMO1 高表达加重肝母细胞瘤恶性程度的相关性研究” （2022-2-56）
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