Low expression of DDX5 is associated with poor prognosis in patients with pancreatic ductal adenocarcinoma

2020 ◽  
pp. jclinpath-2020-207002
Author(s):  
Masashi Morimachi ◽  
Kenichi Hirabayashi ◽  
Yumi Takanashi ◽  
Aya Kawanishi ◽  
Tsubasa Saika ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Islet Cells ◽  
Tumour Size ◽  
Treatment Strategies ◽  
Immunohistochemical Analysis ◽  
Ductal Adenocarcinoma ◽  
Clinicopathological Parameters ◽  
Pancreatic Ducts ◽  
Venous Involvement ◽  
Dead Box

AimsPancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies. Hence, there is a need for new markers and treatment strategies. P68/DEAD box protein 5 (DDX5) is an ATP-dependent RNA helicase of the DEAD box protein family. It is a prognostic marker for several cancers. In this study, we aimed to evaluate the expression and clinical relevance of DDX5 in PDAC.MethodsDDX5 expression in tissue microarray blocks containing 230 PDAC samples was examined using immunohistochemical analysis. DDX5 expression was considered high when more than 50% of the cells were stained and low when less than 50% of the cells were stained. We investigated the association between DDX5 expression and clinicopathological parameters, including patient survival.ResultsThe nuclei of normal pancreatic ducts, normal acinar cells and PDAC cells were stained positive for DDX5 although the intensity and distribution of DDX5 expression varied. Islet cells showed strong and diffuse staining of DDX5. DDX5 expression was low and high in 148 (64.3%) and 82 cases (35.7%), respectively. Low DDX5 expression was significantly associated with an advanced pT factor (pT2–pT3: tumour size,>20 mm), lymphatic involvement, advanced tumour-node-metastasis (TNM) stage (stages IIB, III, and IV), and venous involvement. In addition, the multivariate analysis revealed that DDX5 expression is an independent prognostic factor for PDAC.ConclusionThese results suggest that DDX5 plays an important role in tumour invasiveness and PDAC prognosis.

Relationship between tumour size and outcome in pancreatic ductal adenocarcinoma

2017 ◽  
Vol 104 (5) ◽  
pp. 600-607 ◽  
Author(s):  
D. Ansari ◽  
M. Bauden ◽  
S. Bergström ◽  
R. Rylance ◽  
G. Marko-Varga ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Tumour Size ◽  
Ductal Adenocarcinoma

Adipophilin expression is an indicator of poor prognosis in patients with pancreatic ductal adenocarcinoma: An immunohistochemical analysis

Pancreatology ◽  
2019 ◽  
Vol 19 (3) ◽  
pp. 443-448 ◽  
Author(s):  
Yuki Hashimoto ◽  
Mitsuaki Ishida ◽  
Hironori Ryota ◽  
Tomohisa Yamamoto ◽  
Hisashi Kosaka ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Poor Prognosis ◽  
Immunohistochemical Analysis ◽  
Ductal Adenocarcinoma

Morphological classification of pancreatic ductal adenocarcinoma that predicts molecular subtypes and correlates with clinical outcome

Gut ◽  
2019 ◽  
Vol 69 (2) ◽  
pp. 317-328 ◽  
Author(s):  
Sangeetha N Kalimuthu ◽  
Gavin W Wilson ◽  
Robert C Grant ◽  
Matthew Seto ◽  
Grainne O’Kane ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Molecular Subtypes ◽  
Differentially Expressed Gene ◽  
Biological Significance ◽  
Treatment Strategies ◽  
Ductal Adenocarcinoma ◽  
Rna Seq ◽  
Gene Signatures ◽  
Significant Difference ◽  
Morphological Patterns

IntroductionTranscriptional analyses have identified several distinct molecular subtypes in pancreatic ductal adenocarcinoma (PDAC) that have prognostic and potential therapeutic significance. However, to date, an indepth, clinicomorphological correlation of these molecular subtypes has not been performed. We sought to identify specific morphological patterns to compare with known molecular subtypes, interrogate their biological significance, and furthermore reappraise the current grading system in PDAC.DesignWe first assessed 86 primary, chemotherapy-naive PDAC resection specimens with matched RNA-Seq data for specific, reproducible morphological patterns. Differential expression was applied to the gene expression data using the morphological features. We next compared the differentially expressed gene signatures with previously published molecular subtypes. Overall survival (OS) was correlated with the morphological and molecular subtypes.ResultsWe identified four morphological patterns that segregated into two components (‘gland forming’ and ‘non-gland forming’) based on the presence/absence of well-formed glands. A morphological cut-off (≥40% ‘non-gland forming’) was established using RNA-Seq data, which identified two groups (A and B) with gene signatures that correlated with known molecular subtypes. There was a significant difference in OS between the groups. The morphological groups remained significantly prognostic within cancers that were moderately differentiated and classified as ‘classical’ using RNA-Seq.ConclusionOur study has demonstrated that PDACs can be morphologically classified into distinct and biologically relevant categories which predict known molecular subtypes. These results provide the basis for an improved taxonomy of PDAC, which may lend itself to future treatment strategies and the development of deep learning models.

Expression of GRP78 protein in pancreatic ductal adenocarcinoma and intraductal papillary mucinous neoplasm.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 323-323
Author(s):  
Asha R. Dhanarajan ◽  
Reginald Hill ◽  
Sam G. Pappas ◽  
Gerard J. Abood ◽  
Jennifer Lynn Gnerlich ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Intraductal Papillary Mucinous Neoplasm ◽  
Protein Quality ◽  
Expression Level ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Ducts ◽  
Low Grade ◽  
Ductal Cells ◽  
Mucinous Neoplasm ◽  
Significant Difference

323 Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis due to late detection, aggressive biology and resistance to chemotherapy. Markers for early detection of PDAC and mediators of chemoresistance are poorly understood. GRP78 is a major endoplasmic reticulum (ER) chaperone protein critical for protein quality control of the ER. Increased GRP78 expression promotes in vitro cancer cell survival, progression, and chemoresistance. This study aims to examine expression of GRP78 protein in PDAC and intraductal papillary mucinous neoplasm (IPMN) compared to normal pancreatic ducts using immunohistochemistry (IHC). Methods: The expression of GRP78 was assessed using IHC in 93 sections of formalin-fixed paraffin-embedded tissue: normal ducts (38), low grade IPMN (IPMN-LG, 26), high grade IPMN (IPMN-HG, 9), and PDAC (20). Immunostaining intensity of GRP78 protein was categorized as no or weak staining (0-1+) and strong staining (2-3+). Fisher’s exact test with two tails was performed using the GraphPad statistical software. Results: GRP78 expression was identified in the cytoplasm of normal pancreatic ducts, IPMN and PDAC with a fine granular pattern. All PDAC and IPMN-HG showed strong expression of GRP78 while the normal ductal cells showed only minimal expression of GRP78. 73% of IPMN-LG expresses GRP78 strongly. Statistical analysis revealed a significant difference in GRP78 expression level between normal ductal cells and all three pathological conditions including PDCA, IPMN-HG and IPMN-LG (all p < 0.0001). Conclusions: This study shows that the expression level of GRP78 is significantly increased in PDAC, IPMN-HG and IPMN-LG compared to normal ductal cells. There appears to be a progressive increase in GRP78 expression from IPMN-LG to IPMN-HG and invasive PDAC. Increased GRP78 expression may be a marker for those at risk of developing PDAC. Changes in GRP78 expression over time and its role in PDAC chemoresistance should be further assessed. [Table: see text]

scholarly journals Targeted Therapies for Pancreatic Cancer: Overview of Current Treatments and New Opportunities for Personalized Oncology

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 799 ◽  
Author(s):  
Cédric Leroux ◽  
Georgia Konstantinidou
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Patient Outcomes ◽  
Targeted Therapies ◽  
Median Overall Survival ◽  
Advanced Disease ◽  
Treatment Strategies ◽  
Ductal Adenocarcinoma ◽  
Cancer Associated Fibroblasts ◽  
Personalized Oncology

Cytotoxic chemotherapy remains the only treatment option for most pancreatic ductal adenocarcinoma patients. Currently, the median overall survival of patients with advanced disease rarely exceeds 1 year. The complex network of pancreatic cancer composed of immune cells, endothelial cells, and cancer-associated fibroblasts confers intratumoral and intertumoral heterogeneity with distinct proliferative and metastatic propensity. This heterogeneity can explain why tumors do not behave uniformly and are able to escape therapy. The advance in technology of whole-genome sequencing has now provided the possibility of identifying every somatic mutation, copy-number change, and structural variant in a given cancer, giving rise to personalized targeted therapies. In this review, we provide an overview of the current and emerging treatment strategies in pancreatic cancer. By highlighting new paradigms in pancreatic ductal adenocarcinoma treatment, we hope to stimulate new thoughts for clinical trials aimed at improving patient outcomes.

Characterization of KRAS Mutation in Acinar and Langerhans Islet Cells of Patients With Pancreatic Ductal Adenocarcinoma

Pancreas ◽  
2016 ◽  
Vol 45 (3) ◽  
pp. 337-341 ◽  
Author(s):  
Zhiqiang Wang ◽  
Chuhua Zhang ◽  
Kerry Nagee ◽  
Amir Mohammadi ◽  
Carmela Monteiro
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Kras Mutation ◽  
Islet Cells ◽  
Ductal Adenocarcinoma

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

2018 ◽  
Vol 18 (3) ◽  
pp. 246-251 ◽  
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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