Chen Yajun, Liu Yiming, Wang Menghao
Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Int J Gen Med. 2022 Mar 19;15:3199-3213. doi: 10.2147/IJGM.S353849. eCollection 2022.
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 and by immunohistochemistry in tumor tissues and adjacent normal tissues. In vitro, we silenced and 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 and 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 obviously inhibited the proliferation, migration, and invasion of PANC-1 cells.
Pyroptosis-related genes play important roles in predicting the prognosis of PAAD, and and affect the metastasis of PAAD.
胰腺腺癌（PAAD）是一种高度恶性的肿瘤，预后极差。已证明细胞焦亡在肿瘤预后中起重要作用。然而，PAAD中细胞焦亡相关基因的表达及其与预后的相关性仍不清楚。
在本研究中，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个细胞焦亡相关基因。基于这些差异表达基因（DEGs），在TCGA队列中应用最小绝对收缩和选择算子Cox回归建立了一个五基因特征，并在GEO队列中进行了验证。基于风险模型的DEGs的基因本体论和京都基因与基因组百科全书分析表明，免疫相关的生物学过程和途径得到了富集。在体内，我们通过免疫组织化学检测了肿瘤组织和相邻正常组织中[具体基因1]和[具体基因2]的表达。在体外，我们沉默了[具体基因1]和[具体基因2]以探讨它们对胰腺癌细胞的影响。
低风险组的PAAD患者比高风险组患者具有显著更高的生存可能性。在体内，肿瘤组织中[具体基因1]和[具体基因2]的表达高于相邻正常组织。敲低CASP4显著抑制了PANC-1细胞的侵袭和迁移，但不影响其增殖。敲低[具体基因2]明显抑制了PANC-1细胞的增殖、迁移和侵袭。
细胞焦亡相关基因在预测PAAD的预后中起重要作用，[具体基因]和[具体基因]影响PAAD的转移。
