弥漫性星形细胞瘤弹性的原子力显微镜纳米压痕分析：与肿瘤组织病理学的关系

Atomic Force Microscope Nanoindentation Analysis of Diffuse Astrocytic Tumor Elasticity: Relation with Tumor Histopathology.

作者信息

Tsitlakidis Abraham, Tsingotjidou Anastasia S, Kritis Aristeidis, Cheva Angeliki, Selviaridis Panagiotis, Aifantis Elias C, Foroglou Nicolas

机构信息

First Department of Neurosurgery, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece.

Laboratory of Anatomy, Histology and Embryology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.

出版信息

Cancers (Basel). 2021 Sep 10;13(18):4539. doi: 10.3390/cancers13184539.

DOI:10.3390/cancers13184539

PMID:34572766

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8465072/

Abstract

This study aims to investigate the influence of isocitrate dehydrogenase gene family (IDH) mutations, World Health Organization (WHO) grade, and mechanical preconditioning on glioma and adjacent brain elasticity through standard monotonic and repetitive atomic force microscope (AFM) nanoindentation. The elastic modulus was measured ex vivo on fresh tissue specimens acquired during craniotomy from the tumor and the peritumoral white matter of 16 diffuse glioma patients. Linear mixed-effects models examined the impact of tumor traits and preconditioning on tissue elasticity. Tissues from IDH-mutant cases were stiffer than those from IDH-wildtype ones among anaplastic astrocytoma patients ( = 0.0496) but of similar elasticity to IDH-wildtype cases for diffuse astrocytoma patients ( = 0.480). The tumor was found to be non-significantly softer than white matter in anaplastic astrocytomas ( = 0.070), but of similar elasticity to adjacent brain in diffuse astrocytomas ( = 0.492) and glioblastomas ( = 0.593). During repetitive indentation, both tumor ( = 0.002) and white matter ( = 0.003) showed initial stiffening followed by softening. Stiffening was fully reversed in white matter ( = 0.942) and partially reversed in tumor ( = 0.015). Tissue elasticity comprises a phenotypic characteristic closely related to glioma histopathology. Heterogeneity between patients should be further explored.

摘要

本研究旨在通过标准单调和重复原子力显微镜（AFM）纳米压痕技术，研究异柠檬酸脱氢酶基因家族（IDH）突变、世界卫生组织（WHO）分级以及机械预处理对胶质瘤和相邻脑区弹性的影响。对16例弥漫性胶质瘤患者开颅手术期间获取的新鲜组织标本进行离体弹性模量测量，测量部位包括肿瘤组织和肿瘤周围白质。线性混合效应模型用于检验肿瘤特征和预处理对组织弹性的影响。在间变性星形细胞瘤患者中，IDH突变型病例的组织比IDH野生型病例的组织更硬（P = 0.0496），但在弥漫性星形细胞瘤患者中，其弹性与IDH野生型病例相似（P = 0.480）。研究发现，间变性星形细胞瘤中的肿瘤组织比白质稍软，但差异无统计学意义（P = 0.070），而在弥漫性星形细胞瘤（P = 0.492）和胶质母细胞瘤（P = 0.593）中，肿瘤组织与相邻脑区的弹性相似。在重复压痕过程中，肿瘤组织（P = 0.002）和白质（P = 0.003）均表现出初始变硬，随后变软。白质中的变硬完全恢复（P = 0.942），而肿瘤组织中的变硬部分恢复（P = 0.015）。组织弹性是与胶质瘤组织病理学密切相关的表型特征。患者之间的异质性有待进一步探索。