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基于免疫组化标志物和国际预后指数评分的弥漫性大B细胞淋巴瘤预后列线图模型的建立及临床意义

[Establishment and Clinical Significance of Prognostic Nomogram Model for Diffuse Large B-Cell Lymphoma Based on Immunohistochemistry Markers and International Prognostic Index Scores].

作者信息

Xu Ya-Wen, Zhou Yu-Lan, Kong Fan-Cong, Chen Zhi-Wei, Li Fei

机构信息

Center of Hematology, The First Affiliated Hospital of Nanchang University; Institute of Hematology, Academy of Clinical Medicine of Jiangxi Province; Center of Clinical Trials and Research, Jiangxi Provincial People's Hospital, Nanchang 330006, Jiangxi Province, China.

Center of Hematology, The First Affiliated Hospital of Nanchang University; Institute of Hematology, Academy of Clinical Medicine of Jiangxi Province; Nanchang 330006, Jiangxi Province, China.

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023 Jun;31(3):753-761. doi: 10.19746/j.cnki.issn.1009-2137.2023.03.020.

Abstract

OBJECTIVE

To retrospectively analyze clinical characteristics and survival time of patients with diffuse large B-cell lymphoma (DLBCL), detect prognosis-related markers, and establish a nomogram prognostic model of clinical factors combined with biomarkers.

METHODS

One hundred and thirty-seven patients with DLBCL were included in this study from January 2014 to March 2019 in the First Affiliated Hospital of Nanchang University. The expression of GCET1, LMO2, BCL-6, BCL-2 and MYC protein were detected by immunohistochemistry (IHC), then the influences of these proteins on the survival and prognosis of the patients were analyzed. Univariate and multivariate Cox regression analysis were used to gradually screen the prognostic factors in nomogram model. Finally, nomogram model was established according to the result of multivariate analysis.

RESULTS

The positive expression of GCET1 protein was more common in patients with Ann Arbor staging I/II ( =0.011). Compared with negative patients, patients with positive expression of LMO2 protein did not often show B symptoms ( =0.042), and could achieve better short-term curative effect ( =0.005). The overall survival (OS) time of patients with positive expression of LMO2 protein was significantly longer than those with negative expression of LMO2 protein ( =0.018), though the expression of LMO2 protein did not correlate with progression-free survival (PFS) ( >0.05). However, the expression of GCET1 protein had no significant correlation with OS and PFS. Multivariate Cox regression analysis showed that nomogram model consisted of 5 prognostic factors, including international prognostic index (IPI), LMO2 protein, BCL-2 protein, MYC protein and rituximab. The C-index applied to the nomogram model for predicting 4-year OS rate was 0.847. Moreover, the calibrated curve of 4-year OS showed that nomogram prediction had good agreement with actual prognosis.

CONCLUSION

The nomogram model incorporating clinical characteristics and IHC biomarkers has good discrimination and calibration, which provides a useful tool for the risk stratification of DLBCL.

摘要

目的

回顾性分析弥漫性大B细胞淋巴瘤(DLBCL)患者的临床特征及生存时间,检测预后相关标志物,建立临床因素联合生物标志物的列线图预后模型。

方法

选取2014年1月至2019年3月在南昌大学第一附属医院收治的137例DLBCL患者。采用免疫组织化学(IHC)法检测GCET1、LMO2、BCL-6、BCL-2和MYC蛋白的表达,分析这些蛋白对患者生存及预后的影响。采用单因素和多因素Cox回归分析逐步筛选列线图模型中的预后因素。最后根据多因素分析结果建立列线图模型。

结果

Ann Arbor分期I/II期患者中GCET1蛋白阳性表达更为常见(P = 0.011)。与LMO2蛋白阴性患者相比,LMO2蛋白阳性表达患者较少出现B症状(P = 0.042),且能获得更好的短期疗效(P = 0.005)。LMO2蛋白阳性表达患者的总生存(OS)时间显著长于LMO2蛋白阴性表达患者(P = 0.018),尽管LMO2蛋白表达与无进展生存(PFS)无关(P>0.05)。然而,GCET1蛋白表达与OS和PFS均无显著相关性。多因素Cox回归分析显示,列线图模型由5个预后因素组成,包括国际预后指数(IPI)、LMO2蛋白、BCL-2蛋白、MYC蛋白和利妥昔单抗。应用于预测4年OS率的列线图模型的C指数为0.847。此外,4年OS的校准曲线显示列线图预测与实际预后具有良好的一致性。

结论

结合临床特征和IHC生物标志物的列线图模型具有良好的区分度和校准度,为DLBCL的风险分层提供了有用工具。

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