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CD58表达上调与胰腺导管腺癌患者的临床病理特征及不良预后相关。

Upregulated CD58 is associated with clinicopathological characteristics and poor prognosis of patients with pancreatic ductal adenocarcinoma.

作者信息

Zhang Yalu, Liu Qiaofei, Liu Jingkai, Liao Quan

机构信息

Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.

出版信息

Cancer Cell Int. 2021 Jun 30;21(1):327. doi: 10.1186/s12935-021-02037-0.

Abstract

BACKGROUND

CD58 has been demonstrated to be abnormally expressed in multiple hematopoietic malignancies and solid tumors and plays an essential role in tumorigenesis and progression; however, its clinical significance and prognostic value in pancreatic ductal adenocarcinoma (PDAC) remain unknown.

METHODS

Based on diverse online public databases and 81 PDAC samples of tissue microarray-based immunohistochemistry (IHC), we evaluated CD58 expression in PDAC patients and analyzed its association with clinicopathological characteristics, clinical outcomes, and infiltration of immune cells in PDAC. Furthermore, the correlation between CD58 and the cancer stem cell (CSC)-related, epithelial-mesenchymal transition (EMT)-related, and immune-related markers were detected. Besides, the functional enrichment analysis and related pathways were analyzed and visualized.

RESULTS

CD58 expression was elevated in pancreatitis and PDAC tissues than normal pancreas or adjacent nontumor tissues. The positive cases of CD58 (e.g. more than 50% positive cells) in PDAC account for 95.06% (77/81). Upregulated CD58 in cancer tissues was associated with worse histological grade, larger tumor size, and poorer overall survival and disease-free survival in PDAC patients. Furthermore, Cox multivariate regression analysis revealed that CD58 was an independent prognostic factor in PDAC. CD58 expression was correlated with infiltrations of neutrophils, CD8 T cells, and dendritic cells (DCs). In addition, correlation gene analysis indicated that CD58 expression was strongly correlated with immune-related, EMT-related, and CSC-related markers. Functional enrichment analysis and KEGG pathway manifested that CD58 might be involved in PDAC initiation and progression.

CONCLUSIONS

CD58 expression is upregulated in PDAC tissues and its high expression is notably related to poor survival of PDAC. Therefore, CD58 may serve as a novel and effective marker for predicting the prognosis of PDAC patients.

摘要

背景

已证实CD58在多种血液系统恶性肿瘤和实体瘤中异常表达,并在肿瘤发生和进展中起重要作用;然而,其在胰腺导管腺癌(PDAC)中的临床意义和预后价值仍不清楚。

方法

基于多种在线公共数据库以及81例基于组织芯片免疫组化(IHC)的PDAC样本,我们评估了PDAC患者中CD58的表达,并分析了其与临床病理特征、临床结局以及PDAC中免疫细胞浸润的相关性。此外,检测了CD58与癌症干细胞(CSC)相关、上皮-间质转化(EMT)相关和免疫相关标志物之间的相关性。此外,还进行了功能富集分析并对相关途径进行了分析和可视化。

结果

胰腺炎和PDAC组织中CD58的表达高于正常胰腺或相邻非肿瘤组织。PDAC中CD58阳性病例(例如阳性细胞超过50%)占95.06%(77/81)。癌组织中CD58上调与PDAC患者的组织学分级更差、肿瘤尺寸更大以及总生存期和无病生存期更差相关。此外,Cox多因素回归分析显示CD58是PDAC的独立预后因素。CD58表达与中性粒细胞、CD8 T细胞和树突状细胞(DC)的浸润相关。此外,相关基因分析表明CD58表达与免疫相关、EMT相关和CSC相关标志物密切相关。功能富集分析和KEGG途径表明CD58可能参与PDAC的发生和进展。

结论

PDAC组织中CD58表达上调,其高表达与PDAC患者的不良生存显著相关。因此,CD58可能作为预测PDAC患者预后的一种新型有效标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96ff/8243423/5a2c0db9d139/12935_2021_2037_Fig1_HTML.jpg

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