多发性骨髓瘤患者骨髓活检组织中肿瘤坏死因子α、5-氨基咪唑-4-羟酰胺核糖核酸甲酰基转移酶的表达及临床意义

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摘要目的探讨多发性骨髓瘤(MM)患者骨髓活检组织中肿瘤坏死因子 α(TNF-α)、5-氨基咪唑-4-羟酰胺核糖核酸甲酰基转移酶(ATIC)的表达情况及临床意义。方法收集 2021 年 5 月至 2023 年 6 月在延安市人民医院收治的 90 例 MM 患者作为 MM 组。另采用随机数字表法选取同期住院的 55 例良性血液病患者作为对照组。采用免疫组化法检测骨髓组织中 TNF-α、ATIC 表达水平。 Spearman 秩相关分析 MM 组中 TNF-α 表达与 ATIC 的关系。采用 Kaplan-Meier 曲线分析 TNF-α、 ATIC 表达与预后的关系。采用 Cox 比例风险回归模型分析 MM 患者预后的影响因素。受试者操作特征(ROC)曲线分析骨髓组织中 TNF-α、ATIC 表达对 MM 患者预后的预测价值。结果与对照组相比,MM 组骨髓组织中 TNF-α、ATIC 蛋白阳性率较高(P<0. 05)。 TNF-α、ATIC 阳性表达与国际分期系统( ISS) 有关(P>0. 05)。 Spearman 秩相关分析结果显示,MM 组织中 TNF-α 表达与 ATIC 呈正相关(r = 0. 374,P<0. 001)。生存曲线显示:TNF-α、ATIC 阳性表达组患者 3 年生存率低于阴性表达组患者(P<0. 05)。单因素 Cox 比例风险回归分析显示,ISS 分期Ⅲ期、TNF-α 阳性、ATIC 阳性与 MM 患者死亡有关(P< 0. 05)。多因素 Cox 比例风险回归分析显示,TNF-α 阳性、ATIC 阳性是 MM 患者死亡的危险因素(P<0. 05)。 MM 组骨髓组织中 TNF-α、ATIC 预测 MM 患者预后的曲线下面积(AUC)值分别为 0. 640(95% CI = 0. 523 ~ 0. 756)、0. 714(95% CI = 0. 604 ~ 0. 824),敏感度分别为 67. 57%、72. 97%,特异度分别为 60. 38%、69. 81%。 Hosmer-Lemeshow 拟合优度检验显示:ISS 分期、 TNF-α、ATIC 模型拟合度较好(χ 2 = 3. 061,P= 0. 216)。结论 MM 患者骨髓组织中 TNF-α、ATIC 阳性表达率较高,均为 MM 患者预后的影响因素。

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	1陈玥
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	1 任巧微

关键词 ：多发性骨髓瘤, 肿瘤坏死因子 α, 5-氨基咪唑-4-羟酰胺核糖核酸甲酰基转移酶, 骨髓组织, 生存情况, 影响因素, 预测模型, 预后

Abstract：Objective To investigate the expression and clinical significance of tumor necrosis factor - α TNF - α and 5 - aminoimidazole-4-carboxamide nucleotide transformylase ATIC in bone marrow biopsy tissues of patients with multiple myeloma MM . Method A total of 90 patients with MM admitted to Yan'an People's Hospital between May 2021 and June 2023 were included in the MM group. Additionally 55 patients with benign haematological disorders admitted during the same period were selected using a random number table method to form the control group. Immunohistochemistry was used to detect TNF-α and ATIC in bone marrow tissue. Spearman ' s rank correlation analysis of the relationship between TNF - α expression and ATIC in MM organisations. Kaplan-Meier curve was used to analyze the relationship between TNF - α ATIC and prognosis. The Cox proportional hazards regression model was employed to analyse the prognostic factors influencing patients with MM. Result For the control group the MM group had a higher positive rate of TNF-α and ATIC proteins in bone marrow tissue P<0. 05 . The positive expression of TNF-α and ATIC was associated with the international staging system ISS P>0. 05 . Spearman's rank correlation analysis revealed a positive correlation between TNF-α expression in MM tissue and ATIC r = 0. 374 P<0. 001 . Survival curves showed that the 3-year survival rate of patients in the TNF-α ATIC positive expression group was lower than that of patients in the negative expression group P< 0. 05 . Univariate Cox regression showed that ISS stage Ⅲ TNF-α positivity and ATIC positivity were associated with mortality in MM P<0. 05 . Multivariate Cox proportional hazards regression analysis revealed that TNF-α positivity and ATIC positivity constitute risk factors for mortality in MM patients P<0. 05 . The AUC values of TNF-αand ATIC in bone marrow tissues of the MM group for predicting the prognosis of MM patients were 0. 640 95% CI = 0. 523-0. 756 and 0. 714 95% CI = 0. 604-0. 824 with a sensitivity of 67. 57% and 72. 97% respectively and a specificity of 60. 38% and 69. 81% respectively. The Hosmer - Lemeshow goodness-of-fit test showed that the ISS staging TNF-α and ATIC models fitted better χ 2 = 3. 061 P = 0. 216 . Conclusion The positive expression rates of TNF-α and ATIC in the bone marrow tissue of MM patients are relatively high both serving as prognostic factors for MM patients.

Key words： Multiple myeloma Tumor necrosis factor-α 5-aminoimidazole- 4-carboxamide nucleotide transformylase Bonemarrow tissue Survival status Influencing factors Predictive models Prognosis

基金资助:陕西省自然科学基础研究计划项目(S2020-JC-YB-1284)

通讯作者: 任巧微,电子邮箱:13468877309@ 163. com

引用本文:

1陈玥,2 白顺宁,1 任巧微. 多发性骨髓瘤患者骨髓活检组织中肿瘤坏死因子α、5-氨基咪唑-4-羟酰胺核糖核酸甲酰基转移酶的表达及临床意义[J]. 肿瘤代谢与营养电子杂志, 2025, 12(6): 771-778.
1Chen Yue,2Bai Shunning,1Ren Qiaowei. Expression and clinical significance of TNF-α and ATIC in bone marrow biopsy tissue of patients with multiple myeloma. Electron J Metab Nutr Cancer, 2025, 12(6): 771-778.