WT1-associated protein is a novel prognostic factor in pancreatic ductal adenocarcinoma

Li, Bing‐Qi; Huang, Shuai; Shao, Qianqian; Sun, Jian; Zhou, Li; You, Lei; Zhang, Tai‐Ping; Liao, Quan; Guo, Junchao; Zhao, Yupei

doi:10.3892/ol.2017.5784

Cited by 42 publications

(55 citation statements)

References 61 publications

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“…The results of the present study, to the best of our knowledge, are the first to suggest that strong immunostaining of WT1 in the PDA cytoplasm may be a potentially useful marker to predict the risk of relapse and progression in patients with PDA. Recently, it was reported that the overexpression of WT1-associated protein (WTAP), a ubiquitously expressed nuclear protein, reduced the OS time of PDA patients via a WTAP-WT1 axis (49). This study supports the present findings that cytoplasmic WT1 overexpression in PDA is associated with a worse prognosis.…”

Section: Wt1 Intensity ----------------------------------------------supporting

confidence: 91%

Prognostic significance of Wilms' tumor 1 expression in patients with pancreatic ductal adenocarcinoma

et al. 2018

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The only current curative treatment for patients with pancreatic ductal adenocarcinoma (PDA) is surgical resection, and certain patients still succumb to disease shortly after complete surgical resection. Wilms' tumor 1 (WT1) serves an oncogenic role in various types of tumors; therefore, in the present study, WT1 protein expression in patients with PDA was analyzed and the association with overall survival (OS) and disease-free survival (DFS) time in patients with PDA was assessed following surgical resection. A total of 50 consecutive patients with PDA who received surgical resection between January 2005 and December 2015 at the Jikei University Kashiwa Hospital (Kashiwa, Chiba, Japan) were enrolled. WT1 protein expression in PDA tissue was measured using immunohistochemical staining. Furthermore, laboratory parameters were measured within 2 weeks of surgery, and systemic inflammatory response markers were evaluated. WT1 protein expression was detected in the nucleus and cytoplasm of all PDA cells and in tumor vessels. WT1 exhibited weak staining in the nuclei of all PDA cells; however, the cytoplasmic expression of WT1 levels was classified into four groups: Negative (n=0), weak (n=19), moderate (n=23) and strong (n=8). In patients with PDA, it was demonstrated that the OS and DFS times of patients with weak cytoplasmic WT1 expression were significantly prolonged compared with those of patients with moderate-to-strong cytoplasmic WT1 expression, as determined by log-rank test (P=0.0005 and P=0.0001, respectively). Furthermore, an association between the density of WT1-expressing tumor vessels and worse OS/DFS times was detected. Multivariate analysis also indicated a significant association between the overexpression of WT1 in PDA tissue and worse OS/DFS times. To the best of our knowledge, the present study is the first to demonstrate that moderate-to-strong overexpression of WT1 in the cytoplasm of PDA cells is significantly associated with worse OS/DFS times. Therefore, overexpression of WT1 in the cytoplasm of PDA cells may impact the recurrence and prognosis of patients with PDA following surgical resection. The results further support the development of WT1-targeted therapies to prolong survival in all patients with PDA.

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Section: Wt1 Intensity ----------------------------------------------supporting

confidence: 91%

Prognostic significance of Wilms' tumor 1 expression in patients with pancreatic ductal adenocarcinoma

et al. 2018

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“…Recently, more and more studies have suggested that the abnormal expression of the m 6 A RNA methylation regulators is involved in human cancer. The writer WTAP was reported to be a oncogene in different cancers, such as AML (38), glioblastoma (39), and pancreatic ductal adenocarcinoma (40). The eraser ALKBH5 was observed to be up regulated in glioblastoma stemlike cell (GSCs), leading to the initiation and development of glioblastoma (41).…”

Section: Discussionmentioning

confidence: 99%

Effect of m6A RNA Methylation Regulators on Malignant Progression and Prognosis in Renal Clear Cell Carcinoma

Wang

Zhang

et al. 2020

Front. Oncol.

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Objectives: This study aims to explore the roles of 13 m 6 A RNA methylation regulators in clear cell renal cell carcinoma (ccRCC), and identify a risk signature and prognostic values of m 6 A RNA methylation regulators in ccRCC. Materials and Methods: RNA sequence data of ccRCC was obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed of 13 m 6 A RNA methylation regulators in ccRCC stratified by different clinicopathological characteristics were unveiled using "limma" package in R version 3.6.0. Cox regression and LASSO analyses were conducted to identify the powerful independent prognostic factors in ccRCC associated with overall survival (OS). Protein-protein interaction (PPI) network and correlation analyses of the 13 m 6 A RNA methylation regulators were performed using "STRING" and R package, respectively. Principal component analysis (PCA) was also done using R. In addition, gene ontology (GO), GSEA and Kyoto Encyclopedia of Genes and Genomes pathways were used to functionally annotate the differentially expressed genes in different subgroups. Results: Most of the 13 m 6 A RNA methylation regulators are differentially expressed in ccRCC tissue samples stratified by different clinicopathological characteristics in 537 patients. Next, a risk signature for predicting prognosis of ccRCC patients, was established based on two powerful independent prognostic m 6 A RNA methylation regulators (METTL14 and METTL3). Then, two subgroups (cluster1 and 2) were identified by consensus clustering to the two powerful independent factors and the cluster1 had a poorer prognosis than cluster2. Furthermore, the genes in cluster1 were significantly enriched in cancer-related pathways, biological process, and hallmarks, including "cell adhesion molecules (CAMs)," "leukocyte migration," "Wnt/β-catenin signaling," and so on. Conclusion: M 6 A RNA methylation regulators play important roles in the initiation and progression of ccRCC and provide a novel sight to understand m 6 A RNA modification in ccRCC.

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“…Conversely, more recent studies have shown that the nuclear expression of WT1 in pancreatic ductal adenocarcinoma correlates with gender and tumor stage, while cytoplasmic staining correlates with gender, histological grade and perineural invasion. In addition, the same authors reported that a high nuclear expression of WT1 in pancreatic tumor tissues was significantly associated with poor overall survival, suggesting a possible role for it as a molecular biomarker of a poor prognosis among patients with pancreatic ductal adenocarcinoma [109].…”

Section: Wt1 Expression In Pancreatic Ductal Adenocarcinomasmentioning

confidence: 96%

Immunohistochemical Expression of Wilms’ Tumor 1 Protein in Human Tissues: From Ontogenesis to Neoplastic Tissues

et al. 2019

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The human Wilms’ tumor gene (WT1) was originally isolated in a Wilms’ tumor of the kidney as a tumor suppressor gene. Numerous isoforms of WT1, by combination of alternative translational start sites, alternative RNA splicing and RNA editing, have been well documented. During human ontogenesis, according to the antibodies used, anti-C or N-terminus WT1 protein, nuclear expression can be frequently obtained in numerous tissues, including metanephric and mesonephric glomeruli, and mesothelial and sub-mesothelial cells, while cytoplasmic staining is usually found in developing smooth and skeletal cells, myocardium, glial cells, neuroblasts, adrenal cortical cells and the endothelial cells of blood vessels. WT1 has been originally described as a tumor suppressor gene in renal Wilms’ tumor, but more recent studies emphasized its potential oncogenic role in several neoplasia with a variable immunostaining pattern that can be exclusively nuclear, cytoplasmic or both, according to the antibodies used (anti-C or N-terminus WT1 protein). With the present review we focus on the immunohistochemical expression of WT1 in some tumors, emphasizing its potential diagnostic role and usefulness in differential diagnosis. In addition, we analyze the WT1 protein expression profile in human embryonal/fetal tissues in order to suggest a possible role in the development of organs and tissues and to establish whether expression in some tumors replicates that observed during the development of tissues from which these tumors arise.

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WT1-associated protein is a novel prognostic factor in pancreatic ductal adenocarcinoma

Cited by 42 publications

References 61 publications

Prognostic significance of Wilms' tumor 1 expression in patients with pancreatic ductal adenocarcinoma

Prognostic significance of Wilms' tumor 1 expression in patients with pancreatic ductal adenocarcinoma

Effect of m6A RNA Methylation Regulators on Malignant Progression and Prognosis in Renal Clear Cell Carcinoma

Immunohistochemical Expression of Wilms’ Tumor 1 Protein in Human Tissues: From Ontogenesis to Neoplastic Tissues

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