The crosstalk effect of cancer stem cells in the progression of pediatric medulloblastoma through signaling expression of CD133, CD44, and OCT4 with and without Wnt-b-catenin activation.

IF 1.5 4区 医学 Q4 NEUROSCIENCES
Maher Kurdi, Alaa Alkhotani, Motaz Fadul, Huda Alghefari, Awab T Tayyib, Thamer Alsharif, Majid Almansouri, Yazid Maghrabi, Shadi Alkhayyat, Taghreed Alsinani, Ahmed Bamaga, Saleh Baeesa
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引用次数: 0

Abstract

Introduction: Cancer stem cells (CSCs) are principal drivers in medulloblastoma (MB) initiation, growth, and progression. Our study aimed to explore the expression of CD133, CD44, and OCT4 signaling markers and their effects on the progression of MB.

Material and methods: A retrospective cohort analysis was conducted on brain tissue of 24 pediatric cases of MB from 2016-2020. Protein expression levels of CSC markers CD133, CD44, and OCT4 were evaluated immunohistochemically and their correlation with b-catenin activity was statistically analyzed.

Results: The mean age of patients was 10.2 years (range 3-17), with 18 (75%) males and 6 (25%) females. b-catenin was expressed in 20 (83.3%) tumors, and 4 (16.7%) tumors showed no expression. CD133 was minimally expressed in 6 (25%) tumors and 18 tumors (75%) showed no expression. CD44 was highly expressed in 6 (25%) tumors and 18 (75%) tumors showed minimal to no expression. OCT4 was expressed in all tumors. Despite MBs with positive b-catenin expression and absent CD133 expression having longer progression-free survival (PFS), this impact on PFS did not reach statistical significance ( p = 0.76). However, statistically significant differences in PFS were observed in MBs with positively expressed b-catenin and minimal or no CD44 expression, which showed prolonged PFS ( p = 0.0064). MB patients who did not express CD133 and received combined radiotherapy (RTx) and chemotherapy (CTx) showed longer PFS compared to MB patients with minimal CD133 expression. However, this association was statistically insignificant ( p = 0.42). The impact of CD44 expression and chemoradiation on PFS was statistically significant ( p = 0.0035). MB patients with absent or minimal CD44 expression who received RTx and CTx showed the longest PFS.

Conclusions: Medulloblastomas not expressing CSC markers (CD133, CD44) are associated with prolonged PFS and less resistance to chemoradiation. However, b-catenin is considered the main predictor for prognosis when compared to CSC markers.

在Wnt-b-catenin激活和不激活的情况下,肿瘤干细胞通过CD133、CD44和OCT4信号表达在小儿髓母细胞瘤进展中的串扰效应
肿瘤干细胞(CSCs)是髓母细胞瘤(MB)发生、生长和进展的主要驱动因素。本研究旨在探讨CD133、CD44和OCT4信号标志物的表达及其对MB进展的影响。材料和方法:对2016-2020年24例MB患儿脑组织进行回顾性队列分析。免疫组织化学检测CSC标志物CD133、CD44、OCT4蛋白表达水平,并统计分析其与b-连环蛋白活性的相关性。结果:患者平均年龄10.2岁(3-17岁),男性18例(75%),女性6例(25%)。B-catenin在20例(83.3%)肿瘤中表达,4例(16.7%)肿瘤未表达。CD133在6例(25%)肿瘤中最低表达,18例(75%)肿瘤不表达。CD44在6例(25%)肿瘤中高表达,18例(75%)肿瘤低表达或不表达。OCT4在所有肿瘤中均表达。尽管b-catenin阳性表达和CD133缺失表达的MBs具有更长的无进展生存期(PFS),但这对PFS的影响没有达到统计学意义(p = 0.76)。然而,在阳性表达b-catenin且CD44表达极少或不表达的MBs中,PFS差异有统计学意义,PFS延长(p = 0.0064)。与CD133表达极少的MB患者相比,不表达CD133并接受联合放疗(RTx)和化疗(CTx)的MB患者的PFS更长。然而,这种关联在统计学上不显著(p = 0.42)。CD44表达和放化疗对PFS的影响有统计学意义(p = 0.0035)。CD44表达缺失或极少的MB患者接受RTx和CTx治疗的PFS最长。结论:不表达CSC标志物(CD133, CD44)的髓母细胞瘤与PFS延长和放化疗耐药程度低相关。然而,与CSC标志物相比,b-连环蛋白被认为是预后的主要预测因子。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Folia neuropathologica
Folia neuropathologica 医学-病理学
CiteScore
2.50
自引率
5.00%
发文量
38
审稿时长
>12 weeks
期刊介绍: Folia Neuropathologica is an official journal of the Mossakowski Medical Research Centre Polish Academy of Sciences and the Polish Association of Neuropathologists. The journal publishes original articles and reviews that deal with all aspects of clinical and experimental neuropathology and related fields of neuroscience research. The scope of journal includes surgical and experimental pathomorphology, ultrastructure, immunohistochemistry, biochemistry and molecular biology of the nervous tissue. Papers on surgical neuropathology and neuroimaging are also welcome. The reports in other fields relevant to the understanding of human neuropathology might be considered.
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