Phospholipase A/acyltransferase 4 is a prognostic biomarker and correlated with immune infiltrates in pancreatic cancer

Tian-Hao Li; Yuan-Yang Wang; Bang-Bo Zhao; Cheng Qin; Ze-Ru Li; Wei-Bin Wang

doi:10.1016/j.heliyon.2022.e10416

Phospholipase A/acyltransferase 4 is a prognostic biomarker and correlated with immune infiltrates in pancreatic cancer

Heliyon. 2022 Aug 28;8(9):e10416. doi: 10.1016/j.heliyon.2022.e10416. eCollection 2022 Sep.

Authors

Tian-Hao Li^{1

2}, Yuan-Yang Wang^{1

3}, Bang-Bo Zhao^{1

3}, Cheng Qin^{1

3}, Ze-Ru Li^{1

3}, Wei-Bin Wang^{1

3}

Affiliations

¹ 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.
² Division of Plastic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
³ Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: This study indicated PLAAT4 as a novel prognostic biomarker and an important molecular that mediated immune response in pancreatic cancer.

Keywords: Biomarker; Immune infiltration; Nomogram; PLAAT4; Pancreatic cancer; The cancer genome atlas (TCGA).