A novel refined pyroptosis and inflammasome-related genes signature for predicting prognosis and immune microenvironment in pancreatic ductal adenocarcinoma.
A novel refined pyroptosis and inflammasome-related genes signature for predicting prognosis and immune microenvironment in pancreatic ductal adenocarcinoma.
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DOI：
10.1038/s41598-022-22864-z
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发表时间：
2022-11-01
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
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焦亡是细胞死亡的一种炎症形式，在自身炎症和癌症的发展中起着关键作用。本研究旨在构建胰腺导管腺癌（PDAC）中焦亡和炎性小体相关基因，以预测PDAC的预后。本研究主要基于单因素方差分析、单变量考克斯回归分析、最小绝对收缩和选择算子（LASSO）考克斯回归、风险预后特征、基因集变异分析（GSVA）和免疫微环境分析，使用来自癌症基因组图谱和国际癌症基因组联盟数据库的PDAC数据分析676个焦亡和炎性小体的作用，从Reactome和GeneCards数据库检索的PDAC中的相关基因。最后，我们收集了六对PDAC和匹配的正常相邻组织样本，以验证通过定量实时PCR（qRT-PCR）的签名基因的表达。我们确定了18个候选的焦亡和炎性小体相关基因，这些基因在PDAC患者的病理级别（阶段）之间存在显着差异。单变量考克斯和LASSO分析指出六个基因是构建预后标记的最佳变量，包括ACTA 2、C1 QTNF 9、DNAH 8、GATM、LBP和NGF。风险预后模型的结果表明，1年、3年和5年的AUC均大于0.62。GSVA显示，“糖溶”、“P53通路”、“KRAS信号转导”和“炎症反应”标志基因集与风险评分相关。高风险组与预后不良相关，其特征在于参与抗肿瘤免疫的细胞浸润较低;而具有较高T细胞，NK细胞和巨噬细胞的低风险组显示出相对较好的生存率和细胞溶解评分和炎症评分的显著上调。此外，通过qRT-PCR进一步验证了关键的焦亡和炎性小体相关基因。我们的研究首次揭示了焦亡和炎性小体相关基因在PDAC中的预后作用。同时，PDAC的生物学和预后异质性也得到了证实，加深了我们对该肿瘤的分子认识。
Pyroptosis is an inflammatory form of cell death, which plays a key role in the development of auto-inflammation and cancer. This study aimed to construct a pyroptosis and inflammasome-related genes for predicting prognosis of the pancreatic ductal adenocarcinoma (PDAC). This study was based primarily on the one-way analysis of variance, univariate Cox regression analysis, Least absolute shrinkage and selection operator (LASSO) Cox regression, a risk-prognostic signature, gene set variation analysis (GSVA), and immune microenvironment analysis, using PDAC data from The Cancer Genome Atlas and International Cancer Genome Consortium databases for the analysis of the role of 676 pyroptosis and inflammasome-related genes in PDAC retrieved from the Reactome and GeneCards databases. Lastly, we collected six paired PDAC and matched normal adjacent tissue samples to verify the expression of signature genes by quantitative real-time PCR (qRT-PCR). We identified 18 candidate pyroptosis and inflammasome-related genes that differed significantly between pathologic grades (stages) of PDAC patients. The univariate Cox and LASSO analyses pointed to six genes as the best variables for constructing a prognostic signature, including ACTA2, C1QTNF9, DNAH8, GATM, LBP, and NGF. The results of the risk prognostic model indicated that the AUCs at 1, 3, and 5 years were greater than 0.62. GSVA revealed that ‘GLYCOLYSIS’, ‘P53 PATHWAY’, ‘KRAS SIGNALING UP’, and ‘INFLAMMATORY RESPONSE’ hallmark gene sets were associated with the risk score. The high-risk group was associated with poor prognosis and was characterized by a lower infiltration of cells involved in anti-tumor immunity; whereas the low-risk group with higher T cells, NK cells, and macrophages showed relatively better survival and significantly higher upregulation of cytolytic scores and inflammation scores. Additionally, crucial pyroptosis and inflammasome-related genes were further validated by qRT-PCR. Our study revealed the prognostic role of the pyroptosis and inflammasome-related genes in PDAC for the first time. Simultaneously, the biological and prognostic heterogeneity of PDAC had been demonstrated, deepening our molecular understanding of this tumor.
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影响因子：
6.1
作者：
Li, Hu;Mao, Xinru;Chen, Xingxiang
通讯作者：
Chen, Xingxiang
影响因子：
29
作者：
Maguire OA;Ackerman SE;Szwed SK;Maganti AV;Marchildon F;Huang X;Kramer DJ;Rosas-Villegas A;Gelfer RG;Turner LE;Ceballos V;Hejazi A;Samborska B;Rahbani JF;Dykstra CB;Annis MG;Luo JD;Carroll TS;Jiang CS;Dannenberg AJ;Siegel PM;Tersey SA;Mirmira RG;Kazak L;Cohen P
通讯作者：
Cohen P
DOI：
10.1084/jem.20161707
发表时间：
2017-06-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Daley D;Mani VR;Mohan N;Akkad N;Pandian GSDB;Savadkar S;Lee KB;Torres-Hernandez A;Aykut B;Diskin B;Wang W;Farooq MS;Mahmud AI;Werba G;Morales EJ;Lall S;Wadowski BJ;Rubin AG;Berman ME;Narayanan R;Hundeyin M;Miller G
通讯作者：
Miller G
影响因子：
28.2
作者：
Elyada, Ela;Bolisetty, Mohan;Tuveson, David A.
通讯作者：
Tuveson, David A.
影响因子：
7.5
作者：
Dong, Fangyuan;Yang, Qin;Bao, Zhijun
通讯作者：
Bao, Zhijun