A targeting ligand enhances infectivity and cytotoxicity of an oncolytic adenovirus in human pancreatic cancer tissues

Abstract Background Ubiquitination is a basic post-translational modification of intracellular proteins and can be reversed enzymatically by DUBs (deubiquitinating enzymes). More than 90 DUBs have been identified. Among them, the deubiquitinating enzyme YOD1, a member of the ovarian tumor domain protease (OTUs) subfamily, is involved in the regulation of endoplasmic reticulum (ER)-related degradation pathways. In fact, it is reported that YOD1 is an important proliferation and metastasis-inducing gene, which can stimulate the characteristics of cancer stem cells and maintain circulating tumor cells (CTC). However, the expression level, prognostic effect, biological function and mechanism of YOD1 in pancreatic cancer are still unclear. ResultsIn the GEO and TCGA databases, YOD1 mRNA expression is significantly up-regulated in a variety of human pancreatic cancer tissues. Survival analysis showed that the up-regulation of YOD1 can predict poor prognosis of pancreatic cancer. Cox analysis showed that high YOD1 expression is an independent prognostic factor of pancreatic cancer. ROC analysis shows that YOD1 has significant diagnostic value. The immunohistochemistry (IHC) results showed that the protein expression level of YOD1 in pancreatic cancer tissue was higher than that in neighboring non-pancreatic cancer tissues (P<0.001). In addition, we found that YOD1 expression is negatively correlated with the infiltration level of CD8+ T cells, macrophages, neutrophils and dendritic cells (DC) in pancreatic cancer. The expression of YOD1 has a strong correlation with the different immune marker sets in PAAD. Co-expression network and functional enrichment analysis indicate that YOD1 may participate in the development of pancreatic cancer through cell adhesion molecules, p53, Hippo, TGF-β and other pathways. The experimental results of EDU, Transwell and Western blot indicate that YOD1 is highly expressed in pancreatic cancer cells and pancreatic cancer tissues, and its overexpression can promote the proliferation and metastasis of pancreatic cancer cells.Conclusion Our results indicate that YOD1 may be a useful biomarker for the prognosis of human pancreatic cancer, and it may also be a potential molecular target for the diagnosis and treatment of pancreatic cancer.

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Subcellular protein extraction from human pancreatic cancer tissues

BioTechniques ◽

10.2144/000113090 ◽

2009 ◽

Vol 46 (4) ◽

pp. 297-304 ◽

Cited By ~ 8

Author(s):

Anette Börner ◽

Uwe Warnken ◽

Martina Schnölzer ◽

Jörg von Hagen ◽

Nathalia Giese ◽

...

Keyword(s):

Pancreatic Cancer ◽

Protein Extraction ◽

Human Pancreatic Cancer ◽

Cancer Tissues

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Clinical Significance of Pituitary Tumor Transforming Gene 1 and Transgelin-2 in Pancreatic Cancer

International Journal of Immunopathology and Pharmacology ◽

10.1177/039463201302600114 ◽

2013 ◽

Vol 26 (1) ◽

pp. 147-156 ◽

Cited By ~ 7

Author(s):

H. Lin ◽

Q-L. Chen ◽

X-Y. Wang ◽

W. Han ◽

T-Y. He ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Patients ◽

Clinical Significance ◽

Pituitary Tumor ◽

Human Pancreatic Cancer ◽

Actin Binding ◽

Pituitary Tumor Transforming Gene ◽

Positive Expression ◽

Cancer Tissues ◽

Transforming Gene

Human pituitary tumor transforming gene 1 (PTTG1) is an oncogenic transcription factor that is overexpressed in many malignancies, especially cancers with metastatic potential, while transgelin-2 (TAGLN2) is an actin-binding protein shown to be a tumor suppressor. However, the expression and clinical significance of PTTG1 and TAGLN2 in pancreatic cancer remain unclear. The present study aimed to investigate the expression and clinical significance of PTTG1 and TAGLN2 in human primary pancreatic cancer. Seventy-five cases of human pancreatic cancer tissues were collected. The expression of PTTG1 and TAGLN2 protein was assessed using immunohistochemistry (IHC) through tissue microarray procedure. The clinicopathologic characteristics of all patients were analyzed. As a result, the expression of PTTG1 and TAGLN2 in cancerous tissues showed the positive staining mainly in the cytoplasm, and they were found in cancerous tissues with higher strong reactivity rate compared with the adjacent non-cancer tissues (ANCT) (56.0% vs 22.7%, P<0.001; 100% vs 84%, P=0.002), elevating with the ascending order of tumor malignancy. Furthermore, the positive expression of PTTG1 was associated with the gender of pancreatic cancer patients, but did not correlate with their age, pathological styles, tumor size, tumor sites, TNM staging, perineural infiltration and distant metastasis (each P>0.05). In addition, Spearman rank correlation analysis showed the positive correlation of PTTG1 with TAGLN2 (r=0.624, P<0.001). Taken together, PTTG1 and TAGLN2 are highly expressed in human pancreatic cancer, and the positive expression of PTTG1 is associated with the gender of cancer patients, suggesting that it may represent a potential therapeutic target for the treatment of pancreatic cancer.

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