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鉴定与宫颈癌预后相关的焦亡特征。

Identification of pyroptosis-related signature for cervical cancer predicting prognosis.

机构信息

Department of Gynecology, Southern Medical University Affiliated Maternal and Child Health Hospital of Foshan, Foshan 528000, Guangdong, China.

Department of Maternity Centre, Southern Medical University Affiliated Maternal and Child Health Hospital of Foshan, Foshan 528000, Guangdong, China.

出版信息

Aging (Albany NY). 2021 Nov 27;13(22):24795-24814. doi: 10.18632/aging.203716.

Abstract

Cervical cancer (CC) is one of the most common malignancies encountered in gynecology practice. However, there is a paucity of information about specific biomarkers that assist in the diagnosis and prognosis of CC. Pyroptosis is a form of programmed cell death whose different elements are related to the occurrence, invasion, and metastasis of tumors. However, the role of pyroptosis phenomena in the progression of CC has not yet been elucidated. This study focuses on the development of a pyroptosis-associated prognostic signature for CC using integrated bioinformatics to delineate the relationships among the signature, tumor microenvironment, and immune response of the patients. In this respect, we identified a prognostic signature that depends on eight pyroptosis-related genes (PRGs) that designate with better prognostic survival in the low-risk group (P<0.05) and where AUC values were greater than 0.7. A multi-factor Cox regression analysis indicated that such a signature could be used as an independent prognostic factor, and both the DCA and the Nomogram suggested that the proposed prognostic signature had good predictive capabilities. Interestingly, this prognostic signature can be applied to multiple tumors and thus, is versatile from a clinical point of view. In addition, there were significant differences in the tumor microenvironment and immune infiltration status between the high- and low-risk groups (P<0. 05). The core gene granzyme B (GZMB) was screened and the CC-associated regulatory axis, GZMB/ miR-378a/TRIM52-AS1, was constructed, which may promote CC progression, and further experimentation is needed to validate these results.

摘要

宫颈癌(CC)是妇科临床实践中最常见的恶性肿瘤之一。然而,关于有助于 CC 诊断和预后的特定生物标志物的信息很少。细胞焦亡是一种程序性细胞死亡形式,其不同元素与肿瘤的发生、侵袭和转移有关。然而,细胞焦亡现象在 CC 进展中的作用尚未阐明。本研究使用集成的生物信息学方法开发了一个与细胞焦亡相关的 CC 预后特征,以阐明特征与患者肿瘤微环境和免疫反应之间的关系。在这方面,我们确定了一个依赖于 8 个与细胞焦亡相关的基因(PRGs)的预后特征,该特征在低风险组中指定了更好的预后生存(P<0.05),并且 AUC 值大于 0.7。多因素 Cox 回归分析表明,该特征可作为独立的预后因素,DCA 和 Nomogram 均表明所提出的预后特征具有良好的预测能力。有趣的是,该预后特征可应用于多种肿瘤,因此从临床角度来看具有通用性。此外,高风险组和低风险组之间的肿瘤微环境和免疫浸润状态存在显著差异(P<0.05)。筛选了核心基因 granzyme B(GZMB),并构建了与 CC 相关的调节轴 GZMB/miR-378a/TRIM52-AS1,可能促进 CC 进展,需要进一步实验来验证这些结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68c8/8660613/b8661c5e6d16/aging-13-203716-g001.jpg

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