巢蛋白和CD133作为弥漫性胶质瘤癌干细胞标志物的意义及其与p53表达和异柠檬酸脱氢酶状态的关联。

Significance of Nestin and CD133 as cancer stem cell markers in diffuse glioma and association with p53 expression and IDH status.

作者信息

Selvaraj Sivaranjani, Srinivas Bheemanathi Hanuman, Verma Surendra Kumar, Ms Gopalakrishnan

机构信息

Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) Puducherry, India.

Department of Neurosurgery, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) Puducherry, India.

出版信息

Int J Clin Exp Pathol. 2024 Jul 15;17(7):208-218. doi: 10.62347/YXVS6225. eCollection 2024.

DOI:10.62347/YXVS6225

PMID:39114503

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11301415/

Abstract

BACKGROUND

Recent evidence suggests that the tumor stem cells that are responsible for the pathogenesis of gliomas have similar properties to those of neural stem cells. We have studied two of the most consistently expressed stem cell markers in gliomas, i.e., CD133 and Nestin, and compared them with respect to p53 expression and IDH status.

OBJECTIVES

To assess the level of expression of Nestin and CD133, and identify a correlation among various grades of diffuse glioma with IDH status and expression of p53.

MATERIALS AND METHODS

A cross-sectional retrospective study with 102 subjects for the expression of cancer stem cell markers; CD133 and Nestin and the correlation of their expression with that of p53 and IDH1 status in adult diffuse glioma. The study was conducted in the Departments of Pathology and Neurosurgery. The expression was assessed by immunohistochemistry on formalin-fixed paraffin-embedded sections. The scoring of expression of CD133 and Nestin was adapted from The scoring for p53 was adopted from Results: The diffuse gliomas were graded based on WHO into grade II (30.3%), grade III (28.4%), and grade IV (41.3%). Among WHO grade IV, 59.4% were primary, and 40.4% were secondary glioblastomas. 73% of the diffuse gliomas were IDH mutant, and p53 showed an overall expression of 76.4%. The expression of CD133 and Nestin were compared with the increasing grades of diffuse gliomas, which, when plotted on ROC curves, had AUCs of 0.6806 and 0.6119, respectively. Their expression showed a positive correlation with the IDH status of the tumor.

CONCLUSIONS

Cancer stem cell markers CD133 and Nestin are expressed in diffuse glioma and have a higher expression with increasing WHO grade of malignancy. These cancer stem cell markers have shown significant association with the IDH-1 mutant status of diffuse gliomas. Hence, it can be inferred that diffuse gliomas with a higher expression of CD133 and Nestin have a poorer prognosis. Further, these cancer stem cell markers may be used as therapeutic targets in the future.

摘要

背景

最近的证据表明，负责胶质瘤发病机制的肿瘤干细胞具有与神经干细胞相似的特性。我们研究了胶质瘤中两种最稳定表达的干细胞标志物，即CD133和巢蛋白，并比较了它们在p53表达和异柠檬酸脱氢酶（IDH）状态方面的情况。

目的

评估巢蛋白和CD133的表达水平，并确定不同级别弥漫性胶质瘤与IDH状态及p53表达之间的相关性。

材料与方法

一项横断面回顾性研究，纳入102例受试者，检测癌症干细胞标志物CD133和巢蛋白的表达，以及它们在成人弥漫性胶质瘤中的表达与p53和IDH1状态的相关性。该研究在病理科和神经外科进行。通过免疫组织化学方法在福尔马林固定石蜡包埋切片上评估表达情况。CD133和巢蛋白表达的评分采用[具体方法]，p53的评分采用[具体方法]。结果：弥漫性胶质瘤根据世界卫生组织（WHO）分级为II级（30.3%）、III级（28.4%）和IV级（41.3%）。在WHO IV级中，59.4%为原发性，40.4%为继发性胶质母细胞瘤。73%的弥漫性胶质瘤为IDH突变型，p53的总体表达率为76.4%。将CD133和巢蛋白的表达与弥漫性胶质瘤的分级增加情况进行比较，绘制ROC曲线时，其曲线下面积（AUC）分别为0.6806和0.6119。它们的表达与肿瘤的IDH状态呈正相关。