Li Tian-Hao, Wang Yuan-Yang, Zhao Bang-Bo, Qin Cheng, Li Ze-Ru, Wang Wei-Bin
State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Division of Plastic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Heliyon. 2022 Aug 28;8(9):e10416. doi: 10.1016/j.heliyon.2022.e10416. eCollection 2022 Sep.
Phospholipase A/acyltransferase (PLAAT) family exhibits O- and N-acyltransferase activity and biosynthesize N-acylated ethanolamine phospholipids. Previously, PLAAT4 was seen as a tumor suppressor, but the exact function of PLAAT4 in pancreatic cancer was still unknown. In this study, we investigated the relationship of PLAAT4 and pancreatic cancer.
Using the data from the cancer genome atlas (TCGA), Genotype-Tissue Expression (GTEx) database and Gene Expression Omnibus (GEO) datasets we compared the expression of PLAAT4 in normal and tumor tissues and analyzed the connections between PLAAT4 and several clinicopathological factors. Further, we conducted Gene ontology (GO) analysis, Gene set enrichment analysis (GSEA), single sample gene set enrichment analysis (ssGSEA) and estimate analysis to explore the association between PLAAT4 and biological function and immune infiltration. In addition, Kaplan-Meier (KM) analysis, univariate and multivariate Cox analysis were used to explore the association between PLAAT4 and prognosis. In addition, we plotted a nomogram according to the multivariate cox analysis visualizing the predictive ability of PLAAT4 on prognosis. In addition, we explore the influence of PLAAT4 on malignant behaviors of the pancreatic cancer cells in vitro.
After comparing the expression of PLAAT4 in normal and tumor tissues, we found that the expression of PLAAT4 was significantly high in pancreatic ductal adenocarcinoma (PDAC) samples. In addition, the results of GO and GSEA found that the expression of PLAAT4 was related to cell cycle checkpoints, M phase, regulation by p53, cell cycle mitotic and etc. Further, ssGSEA has shown that PLAAT4 was positively related to the abundance of aDC, Th1 cells, Th2 cells and negatively related to the Th17 cells. Subsequently, KM analysis, univariate and multivariate Cox analysis were used to analyze the correlation between PLAAT4 and prognosis. Additionally, we found that higher expression of PLAAT4 was related to T stage, N stage, histologic grade, etc (P < 0.05) and has a significant correlation with poor Overall Survival (OS), Disease-Specific Survival (DSS) and Progression-Free Interval (PFI). At last, we proved that PLAAT4 contributed to the malignant behaviors of the pancreatic cancer cells.
This study indicated PLAAT4 as a novel prognostic biomarker and an important molecular that mediated immune response in pancreatic cancer.
磷脂酶A/酰基转移酶(PLAAT)家族具有O-和N-酰基转移酶活性,并能生物合成N-酰化乙醇胺磷脂。此前,PLAAT4被视为一种肿瘤抑制因子,但PLAAT4在胰腺癌中的具体功能仍不清楚。在本研究中,我们调查了PLAAT4与胰腺癌的关系。
利用癌症基因组图谱(TCGA)、基因型-组织表达(GTEx)数据库和基因表达综合数据库(GEO)的数据,我们比较了PLAAT4在正常组织和肿瘤组织中的表达,并分析了PLAAT4与几种临床病理因素之间的联系。此外,我们进行了基因本体(GO)分析、基因集富集分析(GSEA)、单样本基因集富集分析(ssGSEA)和估计分析,以探讨PLAAT4与生物学功能和免疫浸润之间的关联。另外,采用Kaplan-Meier(KM)分析、单因素和多因素Cox分析来探讨PLAAT4与预后的关系。此外,我们根据多因素Cox分析绘制了列线图,以直观显示PLAAT4对预后的预测能力。此外,我们还在体外研究了PLAAT4对胰腺癌细胞恶性行为的影响。
在比较了PLAAT4在正常组织和肿瘤组织中的表达后,我们发现PLAAT4在胰腺导管腺癌(PDAC)样本中的表达显著升高。此外,GO和GSEA结果发现,PLAAT4的表达与细胞周期检查点、M期、p53调控、细胞周期有丝分裂等有关。进一步的ssGSEA表明,PLAAT4与aDC、Th1细胞、Th2细胞的丰度呈正相关,与Th17细胞呈负相关。随后,采用KM分析、单因素和多因素Cox分析来分析PLAAT4与预后的相关性。此外,我们发现PLAAT4的高表达与T分期、N分期、组织学分级等有关(P<0.05),并且与总生存期(OS)、疾病特异性生存期(DSS)和无进展生存期(PFI)差显著相关。最后,我们证明了PLAAT4促进了胰腺癌细胞的恶性行为。
本研究表明PLAAT4是一种新的预后生物标志物,也是介导胰腺癌免疫反应的重要分子。