构建一种新型的无附著力细胞凋亡分子分型和评分系统，可区分低级别胶质瘤的不同预后风险和治疗反应性。

Construction of a novel molecular typing and scoring system for anoikis distinguishes between different prognostic risks and treatment responsiveness in low-grade glioma.

机构信息

Department of Oncology, Third Xiangya Hospital, Central South University, Changsha, China.

Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, China.

出版信息

Front Immunol. 2023 Apr 11;14:1105210. doi: 10.3389/fimmu.2023.1105210. eCollection 2023.

DOI:10.3389/fimmu.2023.1105210

PMID:37114037

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10126347/

Abstract

BACKGROUND

The main factors responsible for low-grade glioma (LGG)s' poor prognosis and treatment effectiveness include recurrence and malignant progression. A specific type of programmed cell death, known as anoikis, which is crucial for tumor invasion and metastasis, however, has not yet been investigated in LGGs.

METHODS

We downloaded data of 509 samples from the TCGA-LGG cohort, carried out cluster analysis for typing twice on the basis of 19 anoikis-associated genes, and the subtypes were evaluated the differences in clinicopathological and biological features. ESTIMATE and single-sample gene set enrichment analysis were employed to examine the immunological milieu of LGGs, and enrichment analysis was used to look into the underlying biological mechanisms in LGGs. Cox regression analysis and the Least Absolute Shrinkage and Selection Operator regression algorithm were used to create a prediction scoring system. The scoring system was used for classifying LGG into high- and low- anoikis riskscore (anoiS) groups. The impact of the anoiS on the prognosis, standard treatment, and immunotherapy of patients with LGG was assessed using survival analysis and drug sensitivity analysis. Cell experiments were employed for the verification of the differential expression between LGG cells and normal cells of the anoikis gene team that regard CCT5 as the core.

RESULTS

Based on the expression profiles of the 19 anoikis-associated genes, all individuals with LGG were classified into four subtypes and two macrosubtypes. The different macrosubtypes had significantly different biological characteristics, and the anoirgclusterBD subtype manifested a significantly bad prognosis and a high immune level of infiltration. And subsequent secondary genotyping also showed good prognostic discrimination. We further constructed an anoikis scoring system, anoiS. LGG patients having a high anoiS had a worse prognosis in comparison to those having a low anoiS. The high anoiS group exhibited larger levels of immune infiltration and superior immunotherapy efficacy than the low anoiS group. The high anoiS group was also more susceptible to temozolomide (TMZ) than the low anoiS group, according to a drug sensitivity analysis of TMZ.

CONCLUSION

This study constructed a scoring system for predicting the prognosis of patients with LGG and their responsive to TMZ and immunotherapy.

摘要

背景

导致低级别胶质瘤（LGG）预后不良和治疗效果不佳的主要因素包括复发和恶性进展。一种特定类型的程序性细胞死亡，称为细胞凋亡，对于肿瘤的侵袭和转移至关重要，但尚未在 LGG 中进行研究。

方法

我们从 TCGA-LGG 队列中下载了 509 个样本的数据，基于 19 个与细胞凋亡相关的基因进行了两次聚类分析，并对亚型进行了评估，以比较其在临床病理和生物学特征方面的差异。我们采用 ESTIMATE 和单样本基因集富集分析来评估 LGG 的免疫微环境，并进行富集分析以研究 LGG 中的潜在生物学机制。我们采用 Cox 回归分析和最小绝对收缩和选择算子回归算法来构建预测评分系统。该评分系统用于将 LGG 分为高和低细胞凋亡风险评分（anoiS）组。我们采用生存分析和药物敏感性分析来评估 anoiS 对 LGG 患者预后、标准治疗和免疫治疗的影响。我们通过细胞实验验证了以 CCT5 为核心的细胞凋亡基因团队中 LGG 细胞与正常细胞之间差异表达的验证。

结果

基于 19 个与细胞凋亡相关基因的表达谱，所有 LGG 患者被分为四个亚型和两个宏亚型。不同的宏亚型具有明显不同的生物学特征，而 anoirgclusterBD 亚型表现出明显的不良预后和高免疫浸润水平。随后的二次基因分型也显示出良好的预后区分能力。我们进一步构建了细胞凋亡评分系统，anoiS。与低 anoiS 组相比，高 anoiS 组的 LGG 患者预后更差。高 anoiS 组的免疫浸润水平更高，免疫治疗效果更好。药物敏感性分析表明，高 anoiS 组对替莫唑胺（TMZ）的敏感性高于低 anoiS 组。