急性髓系白血病患者血清ENO1、LAMA4的表达水平及对预后的价值分析

Predictive value of serum ENO1 and LAMA4 for prognosis in patients with acute myeloid leukemia

摘要:

目的 探讨血清烯醇化酶1（ENO1）、层粘连蛋白α4亚基（LAMA4）对急性髓系白血病（AML）患者预后的价值。方法 选取2020年1月—2023年1月中国人民解放军联勤保障部队第九八〇医院收治的221例AML患者的临床资料作为训练集，其中7例患者失访，作为删失数据处理。根据危险度分级标准，将所有患者分为高危组、中危组和低危组，分别有59、105、50例。比较各组血清ENO1、LAMA4水平，Spearman相关性分析血清ENO1、LAMA4水平与AML风险分级的相关性。所有患者经治疗后病情好转出院。出院后随访2年，根据患者生存情况分为生存组和死亡组，分别有171、43例。比较生存组和死亡组临床资料，Cox回归分析AML患者死亡的影响因素，绘制受试者工作特征（ROC）曲线分析各影响因素对AML预后的价值，Delong检验分析各指标间曲线下面积（AUC）差异，采用Kaplan-Meier法进行生存曲线分析，并利用Log-rank χ²检验比较生存曲线的差异。按训练集同标准选取2023年2月—2023年12月该院收治的92例AML患者的临床资料作为验证集，以风暴统计平台绘制列线图、训练集和验证集的ROC曲线、校准曲线及决策曲线。结果 高危组血清ENO1、LAMA4水平均高于中危组和低危组（P <0.05），中危组高于低危组（P <0.05）。Spearman相关性分析显示，血清ENO1水平和LAMA4水平与AML风险等级均呈正相关（r_s =0.610、0.620，均P <0.05）。死亡组高危占比、骨髓原始细胞占比、ENO1、LAMA4水平均高于生存组（P <0.05）。多因素一般Cox回归分析结果显示，ENO1水平高［H^R=1.163（95% CI：1.066，1.270）］和LAMA4水平高［H^R=17.670（95% CI：5.907，52.851）］均为AML患者随访期间死亡的危险因素（P <0.05）。ROC曲线分析结果显示，ENO1、LAMA4联合检测对AML患者预后情况的AUC为0.864（95% CI：0.785，0.888），敏感性为72.09%（95% CI：0.563，0.847），特异性为90.64%（95% CI：0.853，0.946）。ENO1≤59.36 ng/mL组总的生存率高于ENO1>59.36 ng/mL组，LAMA4≤1.59组总生存率高于LAMA4>1.59组（P <0.05）。训练集和验证集ROC曲线的AUC分别为0.860（95% CI：0.730，0.980）、0.840（95% CI：0.750，0.920），预测价值良好。训练集和验证集校准曲线显示，预测价值与实际相仿。决策曲线显示，阈值在30%～90%具有较高正收益。结论 血清ENO1、LAMA4水平越高，AML患者危险度越高，且两者联合预测AML患者预后情况价值较高，具有一定临床推广价值。

Abstract:

Objective To investigate the value of serum enolase 1 (ENO1) and laminin subunit alpha 4 (LAMA4) in predicting the prognosis of patients with acute myeloid leukemia (AML).Methods A total of 221 AML patients admitted to our hospital from January 2020 to January 2023 were retrospectively selected as the training cohort, among which 7 patients lost to follow-up and were treated as censored data. According to the risk classification criteria, all patients were divided into a high-risk group (n = 59), an intermediate-risk group (n = 105), and a low-risk group (n = 50). Serum ENO1 and LAMA4 levels were compared among the three groups, and Spearman correlation analysis was used to assess the correlations between serum ENO1 and LAMA4 levels and the AML risk classification. All patients responded to treatment, and they were discharged after improvement and followed up for 2 years. Based on survival outcomes, patients were divided into the survival group (n = 171) and the death group (n = 43). Clinical data were compared between the survival and death groups, and Cox regression analysis was performed to identify risk factors for mortality in AML patients. Receiver operating characteristic (ROC) curves were plotted to assess the prognostic value of each influencing factor, and the Delong test was used to compare the area under the curve (AUC) differences among indicators. The Kaplan-Meier method was used for survival analysis, and the log-rank test was applied to compare survival curves. According to the same criteria as the training cohort, clinical data of 92 AML patients admitted to our hospital from February 2023 to December 2023 were selected as the validation cohort. Nomograms, ROC curves, calibration curves, and decision curves for both the training and validation cohorts were plotted using the Storm Statistical Platform.Results Serum ENO1 and LAMA4 levels were significantly higher in the high-risk group than in the intermediate- and low-risk groups (P < 0.05), and levels in the intermediate-risk group were also higher than those in the low-risk group (P < 0.05). Spearman correlation analysis showed that serum ENO1 and LAMA4 levels were positively correlated with the AML risk stratification (r_s = 0.610 and 0.620, respectively; both P < 0.05). Compared with the survival group, the death group had a higher proportion of high-risk classification, a higher percentage of bone marrow blasts, and significantly higher ENO1 and LAMA4 levels (all P < 0.05). Multivariable Cox regression analysis demonstrated that elevated ENO1 [H^R = 1.163 (95% CI: 1.066, 1.270) ] and elevated LAMA4 [H^R = 17.670 (95% CI: 5.907, 52.851) ] were independent risk factors for mortality during follow-up in patients with AML (both P < 0.05). ROC curve analysis showed that the combined detection of ENO1 and LAMA4 yielded an AUC of 0.864 (95% CI: 0.785, 0.888), with a sensitivity of 72.09% (95% CI: 0.563, 0.847) and a specificity of 90.64% (95% CI: 0.853, 0.946) for predicting AML prognosis. Patients with ENO1 ≤ 59.36 ng/mL had significantly higher overall survival than those with ENO1 > 59.36 ng/mL, and similar results were observed for LAMA4 (≤ 1.59 vs > 1.59) (both P < 0.05). In the training and validation cohorts, the AUC values were 0.86 (95% CI: 0.73, 0.98) and 0.84 (95% CI: 0.75, 0.92), respectively, indicating good predictive performance. Calibration curves demonstrated good agreement between predicted and observed outcomes in both cohorts. Decision curve analysis showed favorable net clinical benefit across threshold probabilities ranging from 30% to 90%.Conclusion Higher serum ENO1 and LAMA4 levels are associated with higher risk stratification in patients with AML, and the combined assessment of both markers demonstrates a relatively high prognostic predictive value for AML, with potential clinical applicability.