DUOX2 As a Potential Prognostic Marker which Promotes Cell Motility and Proliferation in Pancreatic Cancer

Abstract

DUOX2 has been reported to highly express in several types of cancers. However, the prognostic significance and the biological function of DUOX2 expression with pancreatic cancer (PC) still remain unclear. The present study is aimed at investigating whether DUOX2 could act as a novel biomarker of prognosis and evaluating its effect on PC cell progression. The mRNA and protein expression of DUOX2 in PC cells and tissues were assessed by quantitative real-time PCR (RT-qPCR) and immunohistochemistry. The effect of DUOX2 expression on PC cell motility and proliferation was evaluated in vitro. The correlation between DUOX2 mRNA expression and clinicopathological features and its prognostic significance were analyzed according to the Gene Expression Profiling Interactive Analysis (GEPIA) website based on The Cancer Genome Atlas (TCGA) and the GTEx databases combined with our clinical information. According to bioinformatics analysis, we forecasted the upstream transcription factors (TFs) and microRNA (miRNA) regulatory mechanism of DUOX2 in PC. The expression of DUOX2 at transcriptional and protein level was dramatically increased in PC specimens when compared to adjacent nontumor specimens. Functionally, DUOX2 knockdown inhibited cell motility and proliferation activities. Our clinical data revealed that the patients had better postoperative overall survival (OS) with lower expression of DUOX2, which is consistent with GEPIA data. Multivariate analysis revealed that high DUOX2 expression was considered as an independent prognostic indicator for OS ( P = 0.031 ). Based on Cistrome database, the top 5 TFs of each positively and negatively association with DUOX2 were predicted. hsa-miR-5193 and hsa-miR-1343-3p targeting DUOX2 were forecasted from TargetScan, miRDB, and DIANA-TarBase databases, which were negatively correlated with OS ( P = 0.043 and P = 0.0088 , respectively) and DUOX2 expression ( P = 0.0093 and P = 0.0032 , respectively) in PC from TCGA data. These findings suggest that DUOX2 acts as a promising predictive biomarker and an oncogene in PC, which could be a therapeutic target for PC.

[Retracted] Role of Bioinformatics Analysis in Early Differential Diagnosis of Ovarian Cancer

“…For example, the data description of biological databases often focuses on string sequence (protein sequence and gene sequence), text (gene ontology and functional site description), numerical value (composition and physical and chemical constants), graph (three-dimensional structure), etc. [ 14 , 15 ]. Chemical database descriptions are often based on string (SMILES format), text (MOL file, SDF), numerical value (physical and chemical constants), graph (molecular structure), etc.…”

NSD3, a member of nuclear receptor‐binding SET domain family, is a potential prognostic biomarker for pancreatic cancer

“…As shown, we found total of 148 DEGs (Table S3 ), the top 20 upregulated genes and only 12 downregulated genes of which included COMTD1 (catechol‐o‐methyltransferase domain containing 1), C4orf48 (chromosome 4 open reading frame 48), CCDC85B (coiled‐coil domain containing 85B), CXCL5 (C‐X‐C motif chemokine ligand 5), and others (Figure 6B,C ). We then selected 11 genes related to tumor proliferation to validate their gene expression relationships to NSD3 by Quantitative Real‐time PCR, including CKB (Creatine Kinase B), 29 GADD45G (growth arrest and DNA damage inducible gamma), 30 SCAND1 (SCAN Domain Containing 1), 31 ADAM28 (ADAM metallopeptidase domain 28), 32 ADAM9 (ADAM metallopeptidase domain 9), 33 BIRC3 (Baculoviral IAP Repeat Containing 3), 34 CXCL5 (C‐X‐C motif chemokine ligand 5), 35 DUOX2 (dual oxidase 2), 36 , 37 GABRP (gamma‐aminobutyric acid type A receptor subunit Pi), 38 ITGB6 (integrin subunit beta 6), 39 and RAB11FIP1 (RAB11 family interacting protein 1). 40 As shown, downregulation of NSD3 results in elevated mRNA levels for CKB, GADD45G, and SCAND1, and decreased mRNA expression level of ADAM28, ADAM9, BIRC3, CXCL5, DUOX2, GABRP, ITGB6, and RAB11FIP1 in CFPAC‐1.…”

Overexpression of DUOX2 mediates doxorubicin resistance and predicts prognosis of pancreatic cancer

“…In pancreatic cancer cells, NOX4 promotes ROS signaling and contributes to the epithelial-mesenchymal transition (EMT) induced by transforming growth factor-β (TGF-β) (15). In pancreatic cancer cells, overexpression of DUOX2 predicts poor prognosis and promotes cell invasion and growth (16). However, there is little systematic research on the expression, prognostic significance, and role of NOX family genes in pancreatic cancer.…”