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晚期非小细胞肺癌患者CD47表达、临床特征与预后的相关性

Association between CD47 expression, clinical characteristics and prognosis in patients with advanced non-small cell lung cancer.

作者信息

Arrieta Oscar, Aviles-Salas Alejandro, Orozco-Morales Mario, Hernández-Pedro Norma, Cardona Andrés F, Cabrera-Miranda Luis, Barrios-Bernal Pedro, Soca-Chafre Giovanny, Cruz-Rico Graciela, Peña-Torres María de Lourdes, Moncada-Claudio Guadalupe, Ramirez-Tirado Laura-Alejandra

机构信息

Functional Unit of Thoracic Oncology and Personalized Medicine Laboratory, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.

Pathology Department, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.

出版信息

Cancer Med. 2020 Apr;9(7):2390-2402. doi: 10.1002/cam4.2882. Epub 2020 Feb 11.

Abstract

OBJECTIVE

CD47 is an antiphagocytic molecule that contributes to tumor cell resistance in host immune surveillance. CD47 overexpression correlated with tumor progression and shorter survival in lung cancer. However, the expression and functional significance of CD47 in Non-Small Cell Lung Cancer (NSCLC) has not been completely understood.

MATERIALS AND METHODS

In this retrospective study, CD47 expression was immunohistochemically examined in tumor biopsies from 169 NSCLC patients. The association of CD47 levels (H-score) with clinicopathological characteristics and survival outcomes was evaluated.

RESULTS

CD47 protein was detected in 84% of patients with a median expression of 80% (0-100). Tumor CD47 levels above 1% and 50% were found in 84% and 65.7% of patients, respectively. While, median CD47 staining index was 160 (0-300). Patients were divided into two groups according to CD47 expression (high or low), using a cutoff value of 150. High CD47 expression was associated with wood smoke exposure (71.1% vs 28.9%, P = .013) and presence of EGFR (+) mutations (66.7% vs 33.3%, P = .04). Survival analysis carried out in the whole population did not show any association of CD47 expression and survival outcome. However, in patients with EGFR (+) mutations, CD47 expression was associated with higher progression-free survival (PFS) (12.2 vs. 4.4 months, P = .032). When the survival analysis was performed according to CD47 levels (cut off value: 150), both, PFS and overall survival (OS) were shortened in patients with a high expression of CD47 (10.7 vs. NR, P = .156) and (29.2 vs. NR months P = .023), respectively.

CONCLUSIONS

CD47 overexpression is not a prognostic factor for PFS and OS in NSCLC patients. However, the presence of EGFR mutations and high expression of CD47 were associated with shortened PFS and OS. Coexpression of these markers represents a potential biomarker and characterizes a therapeutic niche for lung cancer.

摘要

目的

CD47是一种抗吞噬分子,在宿主免疫监视中有助于肿瘤细胞抵抗。CD47过表达与肺癌的肿瘤进展和较短生存期相关。然而,CD47在非小细胞肺癌(NSCLC)中的表达及功能意义尚未完全明确。

材料与方法

在这项回顾性研究中,对169例NSCLC患者的肿瘤活检组织进行免疫组织化学检测CD47表达。评估CD47水平(H评分)与临床病理特征及生存结果的相关性。

结果

84%的患者检测到CD47蛋白,中位表达为80%(0 - 100)。分别在84%和65.7%的患者中发现肿瘤CD47水平高于1%和50%。同时,中位CD47染色指数为160(0 - 300)。根据CD47表达(高或低)将患者分为两组,临界值为150。CD47高表达与接触木烟(71.1%对28.9%,P = 0.013)和存在表皮生长因子受体(EGFR)(+)突变(66.7%对33.3%,P = 0.04)相关。对整个人群进行的生存分析未显示CD47表达与生存结果有任何关联。然而,在有EGFR(+)突变的患者中,CD47表达与更高的无进展生存期(PFS)相关(12.2对4.4个月,P = 0.032)。当根据CD47水平(临界值:150)进行生存分析时,CD47高表达患者的PFS和总生存期(OS)均缩短(分别为10.7对未达到,P = 0.156)和(29.2对未达到月,P = 0.023)。

结论

CD47过表达不是NSCLC患者PFS和OS的预后因素。然而,EGFR突变的存在和CD47高表达与缩短的PFS和OS相关。这些标志物的共表达代表一种潜在的生物标志物,并为肺癌确定了一个治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff50/7131854/ac65335b9c7a/CAM4-9-2390-g001.jpg

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