直肠癌患者血清MAGEA3、MAGEA4水平与临床病理特征和预后的关系

The relationship between serum MAGEA3 and MAGEA4 levels and clinical pathological features and prognosis in rectal cancer patients

摘要:

目的 探讨直肠癌患者血清黑色素瘤抗原A3（MAGEA3）、黑色素瘤抗原A4（MAGEA4）水平及其与临床病理特征和预后的关系。方法 选取2020年10月—2021年12月浙江中医药大学附属第二医院94例直肠癌患者作为观察组，另同期选取该院50例健康志愿者作为对照组。检测血清MAGEA3和MAGEA4水平，并分析其与临床病理特征的关系。所有患者术后进行为期3年的随访，Kaplan-Meier法绘制生存曲线，分析血清MAGEA3和MAGEA4的表达水平与预后的关系。采用多因素一般Logistic回归模型分析影响患者预后的独立因素。绘制受试者工作特征（ROC）曲线分析MAGEA3和MAGEA4对直肠癌术后生存的预测价值。结果 观察组血清中MAGEA3和MAGEA4水平均高于对照组（P <0.05）。MAGEA3、MAGEA4水平均与分化程度、TNM分期及淋巴结转移有关（P <0.05），在低分化、Ⅲ期及有淋巴结转移患者中水平更高。Kaplan-Meier分析结果显示，MAGEA3和MAGEA4高水平组的3年总生存率均低于低水平组（P <0.05）。多因素一般Logistic回归分析结果显示，TNM分期为Ⅲ期［O^R =14.463（95% CI：1.915，109.216）］、低分化［O^R =47.179（95% CI：3.175，701.090）］、淋巴结转移［O^R =34.908（95% CI：2.876，423.724）］、血清MAGEA3水平高［O^R =1.121（95% CI：1.018，1.233）］和MAGEA4水平高［O^R =1.283（95% CI：1.070，1.538）］均为直肠癌患者预后不良的危险因素（P <0.05）。ROC曲线分析结果显示，MAGEA3和MAGEA4联合预测时的敏感性为95.7%（95% CI：0.878，0.989），特异性为85.4%（95% CI：0.722，0.939），曲线下面积为0.966（95% CI：0.935，0.997）。结论 血清MAGEA3和MAGEA4在直肠癌患者中均表达上调，且与患者的临床病理特征关系密切。血清MAGEA3、MAGEA4联合检测具有较高的预测价值，可作为直肠癌患者预后的独立指标，为临床提供新的生物标志物，并为免疫治疗提供靶向依据。

Abstract:

Objective This study aims to investigate the levels of melanoma-associated antigen A3 (MAGEA3) and melanoma-associated antigen A4 (MAGEA4) in the serum of rectal cancer patients and their correlation with clinical pathological features and prognosis.Methods This retrospective study included 94 rectal cancer patients admitted to our hospital from October 2020 to December 2021 as the observation group, and 50 healthy volunteers as the control group. Serum MAGEA3 and MAGEA4 protein levels were measured, and their association with clinical pathological features was analyzed. All patients were followed up for 3 years after surgery, and Kaplan-Meier survival curves were used to explore the relationship between serum MAGEA3 and MAGEA4 expression and prognosis. Multivariate logistic regression analysis was used to identify independent prognostic factors, and ROC curves were used to evaluate the predictive value of MAGEA3 and MAGEA4 for postoperative survival in rectal cancer patients.Results Serum levels of MAGEA3 and MAGEA4 were higher in the observation group than in the control group (P < 0.05). There were significant differences in serum MAGEA3 and MAGEA4 levels among patients with different differentiation grades, TNM stages, and lymph node metastasis (P < 0.05), with higher levels observed in patients with poor differentiation, stage III disease, and lymph node metastasis. Kaplan-Meier survival analysis showed that the 3-year overall survival rate was lower in the high MAGEA3 and MAGEA4 expression groups compared to the low expression groups (P < 0.05). Comparison of TNM stage, differentiation grade, lymph node metastasis, and serum MAGEA3 and MAGEA4 levels between the survival and death groups showed statistically significant differences (P < 0.05). Multivariate logistic regression analysis revealed that TNM stage [O^R = 14.463 (95% CI: 1.915, 109.216) ], poor differentiation grade [O^R = 47.179 (95% CI: 3.175, 701.090) ], lymph node metastasis [O^R = 34.908 (95% CI: 2.876, 423.724) ], MAGEA3 [O^R = 1.121 (95% CI: 1.018, 1.233) ], and MAGEA4[O^R = 1.283 (95% CI: 1.070, 1.538) ] were independent risk factors for poor prognosis in rectal cancer patients (P < 0.05). ROC curve analysis showed that When MAGEA3 and MAGEA4 were used in combination, the sensitivity and specificity were 95.7% (95% CI: 0.878, 0.989) and 85.4% (95% CI: 0.722, 0.939), respectively, with an AUC of 0.966 (95% CI: 0.935, 0.997).Conclusion Serum MAGEA3 and MAGEA4 are upregulated in rectal cancer patients and are closely related to clinical pathological features. The combined detection of MAGEA3 and MAGEA4 has high diagnostic value and can serve as an independent prognostic marker for rectal cancer patients. These biomarkers may also provide a basis for immunotherapy targeting.