%A Zhang,Yalu %A Liu,Qiaofei %A Cui,Ming %A Wang,Mengyi %A Hua,Surong %A Gao,Junyi %A Liao,Quan %D 2022 %J Frontiers in Immunology %C %F %G English %K FBXOs,Pancreatic Ductal Adenocarcinoma,Prognostic value,Immune infiltration,Bioinformatics analysis %Q %R 10.3389/fimmu.2021.774435 %W %L %M %P %7 %8 2022-January-03 %9 Original Research %+ Quan Liao,Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College,China,liaoq@pumch.cn %# %! The roles of FBXOs in Pancreatic Cancer %* %< %T Comprehensive Analysis of Expression, Prognostic Value, and Immune Infiltration for Ubiquitination-Related FBXOs in Pancreatic Ductal Adenocarcinoma %U https://www.frontiersin.org/articles/10.3389/fimmu.2021.774435 %V 12 %0 JOURNAL ARTICLE %@ 1664-3224 %X Pancreatic ductal adenocarcinoma (PDAC) is one of the most refractory human malignancies. F-box only proteins (FBXO) are the core components of SKP1-cullin 1-F-box E3 ubiquitin ligase, which have been reported to play crucial roles in tumor initiation and progression via ubiquitination-mediated proteasomal degradation. However, the clinical implications and biological functions of FBXOs in PDAC have not been fully clarified. Herein we perform a comprehensive analysis for the clinical values and functional roles of FBXOs in PDAC using different public databases. We found that FBXO1 (CCNF), FBXO20 (LMO7), FBXO22, FBXO28, FBXO32, and FBXO45 (designated six-FBXOs) were robustly upregulated in PDAC tissues, which predicted an adverse prognosis of PDAC patients. There was a significant correlation between the expression levels of six-FBXOs and the clinicopathological features in PDAC. The transcriptional levels of six-FBXOs were subjected to the influence of promoter methylation levels. There were more than 40% genetic alterations and mutations of six-FBXOs, which affected the clinical outcome of PDAC patients. Furthermore, the expression of six-FBXOs was associated with immune infiltrations and activated status, including B cells, CD8+ T cells, CD4+ T cells, NK cells, macrophages, and dendritic cells. The functional prediction revealed that the six-FBXOs were involved in ubiquitination-related pathways and other vital signaling pathways, such as p53, PI3K/Akt, and Hippo pathway. Therefore, six-FBXOs are the promising prognostic biomarkers or potential targets for PDAC diagnosis and treatment.