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胶质瘤中 pyroptosis 相关亚型的预后特征和肿瘤微环境浸润分析。

Prognostic characterization of the pyroptosis-related subtypes and tumor microenvironment infiltration in glioma.

出版信息

Cancer Biomark. 2023;37(3):161-177. doi: 10.3233/CBM-220362.

Abstract

BACKGROUND

Pyroptosis could regulate tumor cell trafficking, invasion, and metastasis, as well as the tumor microenvironment (TME). However, prognostic characteristics of pyroptosis-related genes (PRGs) and their effect on the progression of glioma remain insufficient.

METHODS

The genetic, transcriptional, and survival data of patients with glioma used for bioinformatic analysis were obtained from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases.

RESULTS

Screening of two different molecular subtypes revealed that PRG variations were associated with characteristics of TME cell infiltration, clinicopathological characteristics, and prognosis of patients with glioma. After Cox regression of differentially expressed genes, a risk score for predicting overall survival (OS) and progression-free survival (PFS) were calculated. Its predictive accuracy in patients with glioma was validated. The high-risk group of PRG signature had a poorer OS than the low-risk group (training cohort, P< 0.001; validation cohort, P< 0.001). A high risk score implies more immune cell infiltration and better immunotherapy response to immune checkpoint blockers. In addition, the differential expression of three pyroptosis-pairs in tumor and normal tissues was identified. Furthermore, the risk score was significantly associated with chemotherapeutic drug sensitivity and cancer stem cell (CSC) index. Subsequently, a highly accurate nomogram was established to facilitate applicability in the preliminary clinical application of risk score.

CONCLUSION

Our findings may provide the basis for future research targeting pyroptosis in glioma and evaluation of prognosis and development of more effective immunotherapy strategies.

摘要

背景

细胞焦亡可调节肿瘤细胞的迁移、侵袭和转移,以及肿瘤微环境(TME)。然而,细胞焦亡相关基因(PRGs)的预后特征及其对胶质瘤进展的影响仍不足。

方法

用于生物信息学分析的胶质瘤患者的遗传、转录和生存数据从中国胶质瘤基因组图谱(CGGA)和癌症基因组图谱(TCGA)数据库中获得。

结果

两种不同分子亚型的筛选表明,PRG 变异与 TME 细胞浸润、临床病理特征和胶质瘤患者预后有关。对差异表达基因进行 Cox 回归后,计算了预测总生存期(OS)和无进展生存期(PFS)的风险评分。验证了其在胶质瘤患者中的预测准确性。PRG 特征的高危组 OS 明显差于低危组(训练队列,P<0.001;验证队列,P<0.001)。高风险评分意味着更多的免疫细胞浸润和更好的免疫治疗对免疫检查点抑制剂的反应。此外,还鉴定了肿瘤和正常组织中三种细胞焦亡对的差异表达。此外,风险评分与化疗药物敏感性和癌症干细胞(CSC)指数显著相关。随后,建立了一个高度准确的列线图,以促进风险评分在初步临床应用中的适用性。

结论

我们的研究结果可能为未来针对胶质瘤细胞焦亡的研究以及预后评估和开发更有效的免疫治疗策略提供依据。

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