A Pyroptosis-Related Gene Panel for Predicting the Prognosis and Immune Microenvironment of Cervical Cancer.
A Pyroptosis-Related Gene Panel for Predicting the Prognosis and Immune Microenvironment of Cervical Cancer.
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用于预测宫颈癌预后和免疫微环境的焦亡相关基因组
DOI：
10.3389/fonc.2022.873725
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发表时间：
2022
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
宫颈癌是女性生殖系统最常见的恶性肿瘤之一。而患者免疫系统的紊乱导致其发病率和死亡率不断上升。焦亡是一种免疫系统相关的程序性细胞死亡途径，通过释放促炎细胞内成分产生全身性炎症。然而，脓毒性相关基因（PRG）在CC中的诊断意义尚不清楚。因此，我们从TCGA数据库中鉴定了52个PRG，并筛选了三个与宫颈癌预后相关的差异表达的热解相关基因（DEPRG）：CHMP 4C，GZMB，TNF。然后使用最小绝对收缩和选择算子（LASSO）回归分析和多变量考克斯回归分析来构建基于三个预后DEPRG的基因面板。根据小组的中位风险评分，将患者分为高风险组和低风险组。根据Kaplan-Meier曲线，两组患者的生存率有很大差异，高危组的生存率明显低于低危组。PCA和t-SNE分析显示，该小组能够将患者区分为高风险组和低风险组。ROC曲线下面积（AUC）显示预后组具有高灵敏度和特异性。风险评分可以作为一个独立的预后因素，使用单变量和多变量考克斯回归分析与临床数据配对。GO和KEGG功能富集的差异表达基因（DEG）在高，低风险组的分析表明，这些基因主要参与免疫反应和炎症细胞趋化。为了进一步说明CC患者中的免疫细胞浸润，我们使用ssGSEA来比较高风险组和低风险组之间的免疫相关细胞和免疫途径活化。在用“CIBERSORT”评估TCGA队列中的免疫细胞浸润后，仍在讨论三种预后DEPRG与免疫相关细胞之间的联系。此外，使用GEPIA数据库和qRT-PCR分析来验证预后DEPRG的表达水平。结论：PRG在肿瘤免疫中起重要作用，可用于预测CC的预后。
Cervical cancer (CC) is one of the most common malignant tumors of the female reproductive system. And the immune system disorder in patients results in an increasing incidence rate and mortality rate. Pyroptosis is an immune system-related programmed cell death pathway that produces systemic inflammation by releasing pro-inflammatory intracellular components. However, the diagnostic significance of pyroptosis-related genes (PRGs) in CC is still unclear. Therefore, we identified 52 PRGs from the TCGA database and screened three Differentially Expressed Pyroptosis-Related Genes (DEPRGs) in the prognosis of cervical cancer: CHMP4C, GZMB, TNF. The least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate COX regression analysis were then used to construct a gene panel based on the three prognostic DEPRGs. The patients were divided into high-and low-risk groups based on the median risk score of the panel. According to the Kaplan-Meier curve, there was a substantial difference in survival rates between the two groups, with the high-risk group’s survival rate being significantly lower than the low-risk group’s. The PCA and t-SNE analyses revealed that the panel was able to differentiate patients into high-and low-risk groups. The area under the ROC curve (AUC) shows that the prognostic panel has high sensitivity and specificity. The risk score could then be employed as an independent prognostic factor using univariate and multivariate COX regression analyses paired with clinical data. The analyses of GO and KEGG functional enrichment of differentially expressed genes (DEGs) in the high-and low-risk groups revealed that these genes were primarily engaged in immune response and inflammatory cell chemotaxis. To illustrate immune cell infiltration in CC patients further, we used ssGSEA to compare immune-related cells and immune pathway activation between the high-and low-risk groups. The link between three prognostic DEPRGs and immune-related cells was still being discussed after evaluating immune cell infiltration in the TCGA cohort with “CIBERSORT.” In addition, the GEPIA database and qRT-PCR analysis were used to verify the expression levels of prognostic DEPRGs. In conclusion, PRGs are critical in tumor immunity and can be utilized to predict the prognosis of CC.
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影响因子：
5.1
作者：
Islami, Farhad;Fedewa, Stacey A.;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
DOI：
10.1016/j.apsb.2021.02.006
发表时间：
2021-09
期刊：
Acta pharmaceutica Sinica. B
影响因子：
--
作者：
Burdette BE;Esparza AN;Zhu H;Wang S
通讯作者：
Wang S
DOI：
10.1007/s00018-017-2686-7
发表时间：
2018-03
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Ostroumov D;Fekete-Drimusz N;Saborowski M;Kühnel F;Woller N
通讯作者：
Woller N
影响因子：
2.4
作者：
Guzman, Valeska B.;Silva, Ismael D. C. G.;Gerbase-DeLima, Maria
通讯作者：
Gerbase-DeLima, Maria
影响因子：
2.6
作者：
Lin, Shu-Li;Wang, Mei;Li, Qing
通讯作者：
Li, Qing