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[弥漫性大B细胞淋巴瘤患者外周血循环肿瘤细胞中不同蛋白表达水平分析及其对复发的预测效能]

[Analysis of different protein expression levels in peripheral blood circulating tumor cells from patients with diffuse large B-cell lymphoma and their predictive efficiency for recurrence].

作者信息

Wang C, Zhou X, Liu G Y, Qu C Y, Yuan C Y, Zhang Y X

机构信息

Department of Hematology, Linyi People's Hospital of Shandong Province, Linyi 276000, China.

Department of Oncology, Linyi People's Hospital of Shandong Province, Linyi 276000, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2023 May 9;103(17):1328-1333. doi: 10.3760/cma.j.cn112137-20220817-01753.

DOI:10.3760/cma.j.cn112137-20220817-01753
PMID:37150683
Abstract

To analyze the expression levels of differentiation cluster 47 (CD47), signal regulatory protein α (SIRP-α), proto-oncogene (MYC) and proliferating cell associated antigen (Ki67) proteins in peripheral blood circulating tumor cells (CTC) from patients with diffuse large B-cell lymphoma and their predictive efficiency for tumor recurrence. The data of 82 patients with diffuse large B-cell lymphoma who were confirmed by histopathology and were in remission after chemotherapy in the Hematology Department of Linyi People's Hospital from January 2018 to January 2021 were retrospectively analyzed. There were 44 males and 38 females, and aged from 50 to 75 (63.8±4.6) years. The patients were divided into recurrent group (=36) and non-recurrent group (=46) according to their recurrence within 1 year after remission. The fasting peripheral venous blood samples (4 ml) from patients in the morning were collected, and the CTC were isolated. The expression levels of CD47, SIRP-α, MYC and Ki67 proteins in CTC were detected by Western blotting. The correlations between CD47 expression level and SIRP-α, MYC and Ki67 expression levels were analyzed by Pearson correlation analysis. The predictive efficiency of CD47, SIRP-α, MYC and Ki67 expression levels on tumor recurrence was evaluated by receiver operating characteristic (ROC) curves, and the areas under the curve (AUC) were calculated. The expression levels of CD47, SIRP-α, MYC and Ki67 in recurrent group were 2.24±0.23, 1.17±0.12, 1.98±0.20 and 2.63±0.27, while those in non-recurrent group were 2.04±0.21, 1.31±0.13, 1.53±0.16 and 2.24±0.25. The expression levels of CD47, MYC and Ki67 in the recurrent group were higher than those in the non-recurrent group, while the expression levels of SIRP-α were lower than those in the non-recurrent group (all <0.001). In 82 patients, the expression levels of CD47, SIRP-α, MYC and Ki67 were 2.13±0.22, 1.25±0.13, 1.73±0.18 and 2.41±0.26, respectively. The expression level of CD47 was negatively correlated with the expression level of SIRP-α (=-0.308, =0.005), but positively correlated with the expression level of MYC and Ki67 (=0.484 and 0.332, =0.012 and 0.003). The sensitivity of CD47, SIRP-α, MYC and Ki67 expression levels in predicting recurrence of diffuse large B-cell lymphoma was 66.7%, 72.2%, 72.2% and 66.7%, with the specificity of 67.4%, 71.7%, 67.4% and 71.7%, and AUC (95%) of 0.694 (0.582-0.791), 0.693 (0582-0.790), 0.714 (0.603-0.808) and 0.709 (0.598-0.804), respectively. The sensitivity of the combined detection of the above four indicators was 83.3%, with the specificity of 78.3% and the AUC (95%) of 0.864 (0.771-0.930), which was higher than those of the individual detection of each indicator (all <0.05). The expression level of CD47 was negatively correlated with the expression level of SIRP-α, but positively correlated with the expression level of MYC and Ki67. The expression levels of CD47, SIRP-α, MYC and Ki67 have certain predictive value for tumor recurrence in patients with diffuse large B-cell lymphoma, and the predictive efficiency of combined detection is higher than single indicator detection.

摘要

分析弥漫性大B细胞淋巴瘤患者外周血循环肿瘤细胞(CTC)中分化簇47(CD47)、信号调节蛋白α(SIRP-α)、原癌基因(MYC)和增殖细胞相关抗原(Ki67)蛋白的表达水平及其对肿瘤复发的预测效能。回顾性分析2018年1月至2021年1月在临沂市人民医院血液科经组织病理学确诊且化疗后缓解的82例弥漫性大B细胞淋巴瘤患者的数据。其中男性44例,女性38例,年龄50~75(63.8±4.6)岁。根据缓解后1年内是否复发将患者分为复发组(n = 36)和未复发组(n = 46)。于清晨采集患者空腹外周静脉血样本(4 ml),分离CTC。采用蛋白质免疫印迹法检测CTC中CD47、SIRP-α、MYC和Ki67蛋白的表达水平。采用Pearson相关分析法分析CD47表达水平与SIRP-α、MYC和Ki67表达水平之间的相关性。采用受试者工作特征(ROC)曲线评估CD47、SIRP-α、MYC和Ki67表达水平对肿瘤复发的预测效能,并计算曲线下面积(AUC)。复发组CD47、SIRP-α、MYC和Ki67的表达水平分别为2.24±0.23、1.17±0.12、1.98±0.20和2.63±0.27,未复发组分别为2.04±0.21、1.31±0.13、1.53±0.16和2.24±0.25。复发组CD47、MYC和Ki67的表达水平高于未复发组,而SIRP-α的表达水平低于未复发组(均P <0.001)。82例患者中,CD47、SIRP-α、MYC和Ki67的表达水平分别为±、±、±和±。CD47的表达水平与SIRP-α的表达水平呈负相关(r = -0.308,P = 0.005),但与MYC和Ki67的表达水平呈正相关(r = 0.484和0.332,P = 0.012和0.003)。CD47、SIRP-α、MYC和Ki67表达水平预测弥漫性大B细胞淋巴瘤复发的敏感度分别为66.7%、72.2%、72.2%和66.7%,特异度分别为67.4%、71.7%、67.4%和71.7%,AUC(95%)分别为()、()、()和()。上述4项指标联合检测的敏感度为83.3%,特异度为78.3%,AUC(95%)为(),均高于各指标单独检测(均P <0.05)。CD47的表达水平与SIRP-α的表达水平呈负相关,但与MYC和Ki67的表达水平呈正相关。CD47、SIRP-α、MYC和Ki67的表达水平对弥漫性大B细胞淋巴瘤患者肿瘤复发具有一定的预测价值,联合检测的预测效能高于单项指标检测。

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