Identification of a Pyroptosis-Related Gene Signature and Effect of Silencing the CHMP4C and CASP4 in Pancreatic Adenocarcinoma.
Identification of a Pyroptosis-Related Gene Signature and Effect of Silencing the CHMP4C and CASP4 in Pancreatic Adenocarcinoma.
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DOI：
10.2147/ijgm.s353849
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发表时间：
2022
影响因子：
2.3
通讯作者：
Wang M
中科院分区：
文献类型：
--
作者：
Chen Y;Liu Y;Wang M
胰腺癌（PAAD）是一种高度恶性的肿瘤，预后极差。焦亡已被证明在肿瘤预后中发挥重要作用。然而，PAAD中焦亡相关基因的表达及其与预后的相关性仍不清楚。在这项研究中，通过“limma”R 包鉴定了正常胰腺组织和 PAAD 组织之间差异表达的 36 个焦亡相关基因。基于这些差异表达基因（DEG），通过在 TCGA 队列中应用最小绝对收缩和选择算子 Cox 回归建立了五基因特征，并在 GEO 队列中进行了验证。基于风险模型的基因本体论和京都基因和基因组百科全书对DEG的分析表明，免疫相关的生物过程和途径得到了丰富。在体内，我们通过免疫组化检测了肿瘤组织和癌旁正常组织中CASP4和CHMP4C的表达。在体外，我们沉默了 CASP4 和 CHMP4C 以探索它们对胰腺癌细胞的影响。低风险组的 PAAD 患者比高风险组的患者表现出显着更高的生存可能性。体内CASP4、CHMP4C在肿瘤组织中的表达量高于癌旁正常组织。 CASP4的敲低显着抑制PANC-1细胞的侵袭和迁移，但不抑制其增殖。 CHMP4C的敲低明显抑制PANC-1细胞的增殖、迁移和侵袭。焦亡相关基因在预测PAAD预后中发挥重要作用，CASP4和CHMP4C影响PAAD的转移。
Pancreatic adenocarcinoma (PAAD) is a highly malignant tumor with an extremely poor prognosis. Pyroptosis has been demonstrated to play an important role in tumor prognosis. However, the expression of pyroptosis-related genes in PAAD and their correlations with prognosis remains unclear. In this study, the 36 pyroptosis-related genes that were differentially expressed between normal pancreatic tissues and PAAD tissues were identified via the “limma” R package. Based on these differentially expressed genes (DEGs), a five-gene signature was established by applying the least absolute shrinkage and selection operator Cox regression in the TCGA cohort and was validated in the GEO cohort. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of DEGs based on the risk model indicated that immune-associated biological processes and pathways were enriched. In vivo, we detected the expressions of CASP4 and CHMP4C by immunohistochemistry in tumor tissues and adjacent normal tissues. In vitro, we silenced CASP4 and CHMP4C to explore their effects on pancreatic cancer cells. PAAD patients in the low-risk group showed significantly higher survival possibilities than those in the high-risk group. The expressions of CASP4 and CHMP4C in tumor tissue were higher than those in the adjacent normal tissues in vivo. The knockdown of CASP4 significantly inhibited the invasion and migration but not the proliferation of PANC-1 cells. The knockdown of CHMP4C obviously inhibited the proliferation, migration, and invasion of PANC-1 cells. Pyroptosis-related genes play important roles in predicting the prognosis of PAAD, and CASP4 and CHMP4C affect the metastasis of PAAD.