AUTHOR=Kuang Wenbin , Wang Xiao , Ding Jiayu , Li Jiaxing , Ji Minghui , Chen Weijiao , Wang Liping , Yang Peng 

TITLE=PTPN2, A Key Predictor of Prognosis for Pancreatic Adenocarcinoma, Significantly Regulates Cell Cycles, Apoptosis, and Metastasis

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.805311

DOI=10.3389/fimmu.2022.805311

ISSN=1664-3224

ABSTRACT=<sec><title>Objective</title><p>This study conducted a comprehensive analysis of the members of the PTPN family and emphasized the key role of <italic>PTPN2</italic> as a potential therapeutic target and diagnostic biomarker in improving the survival rate of PAAD.</p></sec><sec><title>Method</title><p>Oncomine was used to analyze the pan-cancer expression of the PTPN gene family. The Cancer Genome Atlas (TCGA) data as well as Genotype-Tissue Expression (GTEx) data were downloaded to analyze the expression and prognosis of PTPNs. The diagnosis of PTPNs was evaluated by the experimental ROC curve. The protein-protein interaction (PPI) network was constructed by combining STRING and Cytoscape. The genes of 50 proteins most closely related to PTPN2 were screened and analyzed by GO and KEGG enrichment. The differentially expressed genes of <italic>PTPN2</italic> were found by RNA sequencing, and GSEA enrichment analysis was carried out to find the downstream pathways and targets, which were verified by online tools and experiments. Finally, the relationship between <italic>PTPN2</italic> and immune cell infiltration in PAAD, and the relationship with immune score and immune checkpoint were studied.</p></sec><sec><title>Result</title><p>The expression patterns and the prognostic value of multiple PTPNs in PAAD have been reported through bioinformatic analyzes. Among these members, <italic>PTPN2</italic> is the most important prognostic signature that regulates the progression of PAAD by activating JAK-STAT signaling pathway. Comparison of two PAAD cell lines with normal pancreatic epithelial cell lines revealed that <italic>PTPN2</italic> expression was up-regulated as a key regulator of PAAD, which was associated with poor prognosis. Knockdown of <italic>PTPN2</italic> caused a profound decrease in PAAD cell growth, migration, invasion, and induced PAAD cell cycle and apoptosis. In addition, we conducted a series of enrichment analyses to investigate the <italic>PTPN2</italic>-binding proteins and the <italic>PTPN2</italic> expression-correlated genes. We suggest that <italic>STAT1</italic> and <italic>EGFR</italic> are the key factors to regulate <italic>PTPN2</italic>, which are involved in the progression of PAAD. Meanwhile, the silencing of <italic>PTPN2</italic> induced the repression of <italic>STAT1</italic> and <italic>EGFR</italic> expression.</p></sec><sec><title>Conclusion</title><p>These findings provide a comprehensive analysis of the PTPN family members, and for PAAD, they also demonstrate that <italic>PTPN2</italic> is a diagnostic biomarker and a therapeutic target.</p></sec>