The Expression Profile and Textural Characteristics of C595-Reactive MUC1 in Pancreatic Ductal Adenocarcinoma for Targeted Radionuclide Therapy

Improvements in the prognosis of pancreatic ductal adenocarcinoma (PDAC) rely on the development of effective treatments to target advanced disease. Mucin 1 (MUC1) is a transmembrane glycoprotein which is involved in the metastatic progression of PDAC and is a receptor-of-interest for targeted radionuclide therapy. The aim of this study was to determine the feasibility of MUC1-based targeted radionuclide therapy for PDAC, by evaluating the expression profile of MUC1 in different pancreatic cells and tissues using the C595 antibody. MUC1 expression was evaluated in four PDAC cell lines (PANC-1, BxPC-3, CAPAN-1 and AsPC-1) using flow cytometry and immunocytochemistry. Immunohistochemistry was performed on primary and metastatic PDAC, pancreatitis, pancreatic intra-epithelial neoplasia and normal pancreatic tissue samples to identify potential changes in C595-reactive MUC1 expression across different disease groups. C595-reactive MUC1 expression was found to varying degrees in the cell lines (11.5–93.1%). A pixel analysis of the immunohistochemical staining demonstrated highest MUC1 expression in primary PDAC tissue (mean pixel value of 205.4), followed by other pancreatic cancer types (204.9), pancreatic intra-epithelial neoplasia (203.8), metastatic PDAC (201.5), chronic pancreatitis (198.1) and normal pancreatic tissue (191.4). The increased expression in malignant tissues and reduced expression in benign tissues indicate that C595-reactive MUC1 is a potential target for targeted radionuclide therapy of PDAC.

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Utility of CT Radiomics Features in Differentiation of Pancreatic Ductal Adenocarcinoma From Normal Pancreatic Tissue

American Journal of Roentgenology ◽

10.2214/ajr.18.20901 ◽

2019 ◽

Vol 213 (2) ◽

pp. 349-357 ◽

Cited By ~ 27

Author(s):

Linda C. Chu ◽

Seyoun Park ◽

Satomi Kawamoto ◽

Daniel F. Fouladi ◽

Shahab Shayesteh ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Pancreatic Tissue ◽

Ductal Adenocarcinoma ◽

Normal Pancreatic Tissue

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Immunohistochemical expression of NEDD9, E-cadherin and γ-catenin and their prognostic significance in pancreatic ductal adenocarcinoma (PDAC)

Bosnian Journal of Basic Medical Sciences ◽

10.17305/bjbms.2018.2378 ◽

2018 ◽

Vol 18 (3) ◽

pp. 246-251 ◽

Cited By ~ 2

Author(s):

Petra Radulović ◽

Božo Krušlin

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Patient Survival ◽

Negative Impact ◽

Prognostic Significance ◽

Pancreatic Tissue ◽

Ductal Adenocarcinoma ◽

Clinicopathological Parameters ◽

Rank Test ◽

Normal Pancreatic Tissue ◽

E Cadherin

Extensive research is being conducted to identify novel diagnostic, predictive and prognostic biomarkers for pancreatic ductal adenocarcinoma (PDAC), as only a few markers have been routinely used so far with limited success. Our aim was to assess the expression of neural precursor cell expressed developmentally down-regulated protein 9 (NEDD9), E-cadherin, and γ-catenin in PDAC in relation to clinicopathological parameters and patient survival. We also investigated if there is a correlation of NEDD9 expression with E-cadherin or γ-catenin. The protein expression was determined by immunohistochemistry in 61 PDAC and 61 samples of normal pancreatic tissue. The log rank test and Kaplan-Meier survival curve were used for survival analysis. E-cadherin and γ-catenin expressions were reduced in PDAC, and completely retained in normal pancreatic tissue. Expression of NEDD9 was significantly increased in PDAC (strong expression in 78.7% of cases and moderate in 21.3%) and reduced in normal pancreatic tissue (strong positivity in 45.9% of cases, moderate in 31.1%, and weak in 23%). There was a positive correlation between reduced E-cadherin and γ-catenin expression in PDAC (p = 0.015). The loss or reduced expression of E-cadherin had a negative impact on patient survival (p = 0.020). A negative correlation between E-cadherin expression and tumor grade was also observed (p = 0.011). Decreased E-cadherin expression was more common in male patients with PDAC (81.3% vs. 60% for females, p = 0.005). γ-catenin and NEDD9 expressions were not statistically correlated with tumor stage and grade, gender, nor with patient survival. Our results support the role of NEDD9, E-cadherin and γ-catenin proteins in PDAC, but further research should clarify in detail their mechanism of action in pancreatic cancer.

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The WNT5A/ROR2 signaling pathway in pancreatic ductal adenocarcinoma (PDAC)

10.21203/rs.3.rs-34447/v1 ◽

2020 ◽

Author(s):

Lydia Remtisch ◽

Georg Wiltberger ◽

Katrin Schierle ◽

Moulla Yousef ◽

René Thieme ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Signaling Pathway ◽

Prognostic Value ◽

Expression Patterns ◽

Tumor Stroma ◽

Pancreatic Tissue ◽

Ductal Adenocarcinoma ◽

Normal Pancreatic Tissue ◽

Variable Expression ◽

Wnt5a Expression

Abstract Background WNT5A/ROR2 signaling pathway has been shown to be involved in many human cancers. Its role in pancreatic ductal adenocarcinoma (PDAC) has not been clarified yet. The aim of this study was to determine the prognostic value of WNT5A-expression in conjunction with the ROR2-expression in the same tumor tissues of PDAC patients. Methods We retrospectively analyzed the expression of WNT5A and ROR2 in 117 paraffin-embedded PDAC specimens following surgical pancreatic resection by immunohistochemistry. The prognostic value of WNT5A and ROR2 was assessed using Kaplan-Meier survival curves and multivariate COX regression-models. Results High ROR2-expression was detected in 65.8% (77/117) of PDAC-tumors, in 28.2% (33/117) in tumor-stroma, and in 71.1% (65/90) of normal pancreatic tissue. High WNT5A-expression was found in 76.9% (90/117) of tumors, in 59.0% (69/117) of tumor-stroma, and in 83.0% (73/88) of normal pancreatic tissue. Spearman's correlation co-efficiency demonstrated weak association between ROR2- and WNT5A-expression in tumor (r = 0.184; p = 0.047), and no association in stroma (r = 0.036; p = 0.699). Multivariate analysis showed that regional lymph node invasion and differentiation were independent prognostic factors of survival, while ROR2- and WNT5A-expression not. Conclusions Variable expression patterns for ROR2 and WNT5A were demonstrated in PDAC and normal pancreatic tissues suggesting a role for WNT5A/ROR2 signalling pathway, not only in PDAC but also in the normal pancreatic tissue during inflammation. The lack of prognostic significance for ROR2- and WNT5A-expression in our cohort, either alone or in subgroup analysis, signifies the complexity of their role in PDAC, which is highly dependent on the different molecular receptor-ligand tissue contexts.

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Microarray expression profile of circular RNAs in human pancreatic ductal adenocarcinoma

Genomics Data ◽

10.1016/j.gdata.2015.07.017 ◽

2015 ◽

Vol 5 ◽

pp. 385-387 ◽

Cited By ~ 53

Author(s):

Shibin Qu ◽

Wenjie Song ◽

Xisheng Yang ◽

Jianlin Wang ◽

Ruohan Zhang ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Expression Profile ◽

Ductal Adenocarcinoma ◽

Circular Rnas ◽

Microarray Expression ◽

Microarray Expression Profile

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Repression of MUC1 promotes expansion and suppressive function of myeloid-derived suppressor cells in pancreatic ductal adenocarcinoma and breast cancer murine models

10.1101/2020.12.07.415299 ◽

2020 ◽

Author(s):

S. Mahnaz ◽

L. Das Roy ◽

M. Bose ◽

C. De ◽

S. Nath ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Microenvironment ◽

Pancreatic Ductal Adenocarcinoma ◽

Signaling Pathways ◽

Suppressor Cells ◽

Ductal Adenocarcinoma ◽

Myeloid Derived Suppressor Cells ◽

Mucin 1 ◽

Transmembrane Glycoprotein ◽

The Impact

ABSTRACTMyeloid-derived suppressor cells (MDSCs) are immature myeloid cells that are responsible for immunosuppression in tumor microenvironment. Here we report the impact of mucin 1 (MUC1), a transmembrane glycoprotein, on proliferation and functional activity of MDSCs. To determine the role of MUC1 in MDSC phenotype, we analyzed MDSCs derived from wild type (WT) and MUC1-knockout (MUC1KO) mice bearing pancreatic ductal adenocarcinoma KCKO and breast cancer C57MG xenografts. We observed enhanced tumor growth in MUC1KO mice compared to WT mice in both pancreatic KCKO and breast C57MG cancer models due to increased MDSC population and enrichment of Tregs in tumor microenvironment. Our current study shows that knockdown of MUC1 in MDSCs promotes proliferation and immature suppressive phenotype indicated by increased level of iNOS, ARG1 activity and TGF-β secretion under cancer conditions. Increased activity of MDSCs leads to repression of IL-2 and IFN-ɣ production by T-cells. We were able to find that MDSCs from MUC1KO mice have higher levels of c-Myc and activated pSTAT3 as compared to MUC1 WT mice, that are signaling pathways leading to increased survival, proliferation and prevention of maturation. In summary, MUC1 regulates signaling pathways that maintain immunosuppressive properties of MDSCs. Thus, immunotherapy must target only tumor associated MUC1 on epithelial cells and not MUC1 on hematopoietic cells to avoid expansion and suppressive functions of MDSC.

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Abstract PO-052: A pilot study of miRNA expression profile in surgically resected pancreatic ductal adenocarcinoma: Initial report from a bi-institutional cohort

10.1158/1538-7445.panca21-po-052 ◽

2021 ◽

Author(s):

Luca Pompella ◽

Michela Falco ◽

Carlo Caputo ◽

Anna Grimaldi ◽

Giuseppe Tirino ◽

...

Keyword(s):

Pilot Study ◽

Pancreatic Ductal Adenocarcinoma ◽

Expression Profile ◽

Mirna Expression ◽

Mirna Expression Profile ◽

Ductal Adenocarcinoma ◽

Initial Report

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MicroRNA-132 Plays an Independent Prognostic Role in Pancreatic Ductal Adenocarcinoma and Acts as a Tumor Suppressor

Technology in Cancer Research & Treatment ◽

10.1177/1533033818824314 ◽

2019 ◽

Vol 18 ◽

pp. 153303381882431 ◽

Cited By ~ 3

Author(s):

Yan Chen ◽

Huiyun Zhu ◽

Yuqiong Wang ◽

Yingxiao Song ◽

Pingping Zhang ◽

...

Keyword(s):

Transcription Factor ◽

Protein Kinase ◽

Prognostic Factor ◽

Pancreatic Ductal Adenocarcinoma ◽

Cell Lines ◽

Mitogen Activated Protein Kinase ◽

Ductal Adenocarcinoma ◽

Adenocarcinoma Cell ◽

Nuclear Transcription Factor ◽

Mitogen Activated Protein

The role of microRNA-132 in human pancreatic ductal adenocarcinomas is still ambiguous. We explored the association between microRNA-132 and pancreatic ductal adenocarcinoma prognosis. The expression of microRNA-132 in 50 pancreatic ductal adenocarcinoma tissue samples and pancreatic ductal adenocarcinoma cell lines was examined, and the association between its expression and pancreatic ductal adenocarcinoma prognosis was assessed. Functional analysis and factors downstream of microRNA-132 were investigated. Kaplan-Meier survival curves showed that high expression of microRNA-132 was a significant prognostic factor for 1-year survival of patients with pancreatic ductal adenocarcinoma ( P = .028). Multivariate analysis for overall survival indicated that high expression of microRNA-132 was an independent prognostic factor for patients with pancreatic ductal adenocarcinoma ( P = .044). Low expression of microRNA-132 was associated with poor prognosis in pancreatic ductal adenocarcinoma. Ectopic expression of microRNA-132 significantly inhibited proliferation and promoted apoptosis of 2 pancreatic ductal adenocarcinoma cell lines. Bioinformatic analysis revealed that microRNA-132 may exert its effects on pancreatic ductal adenocarcinoma through downregulating mitogen-activated protein kinase 3 and nuclear transcription factor Y subunit α. The results of this study further our understanding of the relationship between microRNA-132 and pancreatic ductal adenocarcinoma by showing that microRNA-132 might inhibit the progression of pancreatic ductal adenocarcinoma by regulating mitogen-activated protein kinase and nuclear transcription factor Y subunit alpha.

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