A study of Smad4, Smad6 and Smad7 in Surgically Resected Samples of Pancreatic Ductal Adenocarcinoma and Their Correlation with Clinicopathological Parameters and Patient Survival

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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Expression of microRNA-218 in human pancreatic ductal adenocarcinoma and its correlation with tumor progression and patient survival

Journal of Surgical Oncology ◽

10.1002/jso.23475 ◽

2013 ◽

Vol 109 (2) ◽

pp. 89-94 ◽

Cited By ~ 20

Author(s):

Ziman Zhu ◽

Yuefang Xu ◽

Jundong Du ◽

Jingwang Tan ◽

Huabao Jiao

Keyword(s):

Tumor Progression ◽

Pancreatic Ductal Adenocarcinoma ◽

Patient Survival ◽

Ductal Adenocarcinoma

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Nuclear UCHL5 Expression Associates with Increased Patient Survival in Pancreatic Ductal Adenocarcinoma

Pancreatology ◽

10.1016/j.pan.2017.05.186 ◽

2017 ◽

Vol 17 (3) ◽

pp. S58-S59

Author(s):

Kapo Saukkonen ◽

Leena Arpalahti ◽

Jaana Hagström ◽

Harri Mustonen ◽

Hanna Seppänen ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Patient Survival ◽

Ductal Adenocarcinoma

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Genetic Alterations of K-ras, p53, c-erbB-2, and DPC4 in Pancreatic Ductal Adenocarcinoma and Their Correlation With Patient Survival

Pancreas ◽

10.1097/mpa.0b013e31825b6ab0 ◽

2013 ◽

Vol 42 (2) ◽

pp. 216-222 ◽

Cited By ~ 55

Author(s):

Sang Hyun Shin ◽

Song Cheol Kim ◽

Seung-Mo Hong ◽

Young Hoon Kim ◽

Ki-Byung Song ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Patient Survival ◽

Genetic Alterations ◽

Ductal Adenocarcinoma

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The effect of neuroendocrine differentiation on the survival of patients diagnosed with pancreatic ductal adenocarcinoma

Experimental and Clinical Gastroenterology ◽

10.31146/1682-8658-ecg-184-12-38-44 ◽

2020 ◽

pp. 38-44

Author(s):

O. I. Kit ◽

E. M. Franciyanc ◽

I. S. Derizhanova ◽

N. S. Karnaukhov ◽

M. A. Kuznetsova ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Chromogranin A ◽

Pancreatic Tumor ◽

Prognostic Markers ◽

Patient Survival ◽

Immunohistochemical Study ◽

Neuroendocrine Differentiation ◽

Ductal Adenocarcinoma ◽

Ki 67 ◽

Cancer Research Institute

Purpose of the study. Determine the frequency of MiNeN among pancreatic carcinomas and analyze the survival rate of patients depending on the percentage of cells with neuroendocrine differentiation in the tumor.Materials and methods. The current study included 31 patients with a pancreatic tumor who received surgical treatment at the Rostov Cancer Research Institute. An immunohistochemical study was conducted on biomarkers of chromogranin A, synaptophysin, and ki-67 for these patients. Based on the data obtained, 4 groups for neuroendocrine differentiation were identified.Results. The direct effect of neuroendocrine differentiation on the survival of patients with histologically confirmed pancreatic ductal adenocarcinoma has been proven. Among the sample of 31 patients, neuroendocrine differentiation was revealed in 24 cases (77%), of which 3 cases of MiNeN (10.3%) were detected. It is also proven relationship between neuroendocrine and patient survival, where an increase percent of positive cells in tumors (chromogranin A or synaptophysin) means a better prognosis. Chromogranin A is a more significant predictor of survival compared to synaptophysin. The largest difference in survival was between negative expression of chromogranin A and the presence of more than 1% positive cells in the tumor.Conclusion. We supposed that it is necessary to use neuroendocrine markers (chromogranin A and synaptophysin) in the diagnosis of ductal adenocarcinomas, even without histological signs of neuroendocrine differentiation. This will allow for a larger amount of data to determine their significance as prognostic markers.

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Serum Metabolomic and Lipoprotein Profiling of Pancreatic Ductal Adenocarcinoma Patients of African Ancestry

Metabolites ◽

10.3390/metabo11100663 ◽

2021 ◽

Vol 11 (10) ◽

pp. 663

Author(s):

Nnenna Elebo ◽

Jones Omoshoro-Jones ◽

Pascaline N. Fru ◽

John Devar ◽

Christiaan De Wet van Zyl ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Patient Survival ◽

African Ancestry ◽

Metabolic Phenotype ◽

Ductal Adenocarcinoma ◽

Tumour Stage ◽

Nmr Spectrum ◽

Spearman’S Correlation ◽

Patient Survival Time ◽

Healthy Participants

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a characteristic dysregulated metabolism. Abnormal clinicopathological features linked to defective metabolic and inflammatory response pathways can induce PDAC development and progression. In this study, we investigated the metabolites and lipoproteins profiles of PDAC patients of African ancestry. Nuclear Magnetic Resonance (NMR) spectroscopy was conducted on serum obtained from consenting individuals (34 PDAC, 6 Chronic Pancreatitis, and 6 healthy participants). Seventy-five signals were quantified from each NMR spectrum. The Liposcale test was used for lipoprotein characterization. Spearman’s correlation and Kapan Meier tests were conducted for correlation and survival analyses, respectively. In our patient cohort, the results demonstrated that levels of metabolites involved in the glycolytic pathway increased with the tumour stage. Raised ethanol and 3-hydroxybutyrate were independently correlated with a shorter patient survival time, irrespective of tumour stage. Furthermore, increased levels of bilirubin resulted in an abnormal lipoprotein profile in PDAC patients. Additionally, we observed that the levels of a panel of metabolites (such as glucose and lactate) and lipoproteins correlated with those of inflammatory markers. Taken together, the metabolic phenotype can help distinguish PDAC severity and be used to predict patient survival and inform treatment intervention.

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

Journal of Clinical Pathology ◽

10.1136/jclinpath-2020-207002 ◽

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.

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Nuclear ubiquitin C-terminal hydrolase L5 expression associates with increased patient survival in pancreatic ductal adenocarcinoma

Tumor Biology ◽

10.1177/1010428317710411 ◽

2017 ◽

Vol 39 (6) ◽

pp. 101042831771041 ◽

Cited By ~ 7

Author(s):

Leena Arpalahti ◽

Kapo Saukkonen ◽

Jaana Hagström ◽

Harri Mustonen ◽

Hanna Seppänen ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Patient Survival ◽

Ductal Adenocarcinoma

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Molecular and Metabolic Subtypes Correspondence for Pancreatic Ductal Adenocarcinoma Classification

Journal of Clinical Medicine ◽

10.3390/jcm9124128 ◽

2020 ◽

Vol 9 (12) ◽

pp. 4128

Author(s):

Pilar Espiau-Romera ◽

Sarah Courtois ◽

Beatriz Parejo-Alonso ◽

Patricia Sancho

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Metabolic Profile ◽

Patient Survival ◽

Metabolic Reprogramming ◽

Ductal Adenocarcinoma ◽

Patient Stratification ◽

Molecular Alterations ◽

Genomic Signatures ◽

Amino Acid Consumption ◽

Acid Consumption

Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is an extremely lethal disease due to late diagnosis, aggressiveness and lack of effective therapies. Considering its intrinsic heterogeneity, patient stratification models based on transcriptomic and genomic signatures, with partially overlapping subgroups, have been established. Besides molecular alterations, PDAC tumours show a strong desmoplastic response, resulting in profound metabolic reprogramming involving increased glucose and amino acid consumption, as well as lipid scavenging and biosynthesis. Interestingly, recent works have also revealed the existence of metabolic subtypes with differential prognosis within PDAC, which correlated to defined molecular subclasses in patients: lipogenic subtype correlated with a classical/progenitor signature, while glycolytic tumours associated with the highly aggressive basal/squamous profile. Bioinformatic analyses have demonstrated that the representative genes of each metabolic subtype are up-regulated in PDAC samples and predict patient survival. This suggests a relationship between the genetic signature, metabolic profile, and aggressiveness of the tumour. Considering all this, defining metabolic subtypes represents a clear opportunity for patient stratification considering tumour functional behaviour independently of their mutational background.

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Metabolic and Lipoprotein Profiling of Pancreatic Ductal Adenocarcinoma Patients of African Ancestry

10.20944/preprints202108.0235.v1 ◽

2021 ◽

Author(s):

Nnenna Elebo ◽

Jones Omoshoro-Jones ◽

Pascaline Fonteh-Fru ◽

John Devar ◽

Christiaan De Wet van Zyl ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Patient Survival ◽

African Ancestry ◽

Metabolic Phenotype ◽

Ductal Adenocarcinoma ◽

Treatment Intervention ◽

Tumour Stage ◽

Nmr Spectrum ◽

Patient Survival Time ◽

Healthy Participants

Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a characteristic dysregulated metabolism. Abnormal clinicopathological features linked to defective metabolic and inflammatory response pathways can induce PDAC development and progression. In this study, we investigated the metabolites and lipoproteins profiles of PDAC patients of African ancestry. Nuclear Magnetic Resonance (NMR) spectroscopy was conducted on serum obtained from consenting individuals (34 PDAC, 6 Chronic Pancreatitis, and 6 healthy participants). Seventy-five signals were quantified from each NMR spectrum. The Liposcale test was used for lipoprotein characterization. Spearman’s correlation and Kapan Meier tests were conducted for correlation and survival analyses respectively. In our patient cohort, the results demonstrated that levels of metabolites involved in the glycolytic pathway increased with the tumour stage. Raised ethanol and 3-hydroxybutyrate were independently correlated with a shorter patient survival time, irrespective of tumour stage. Furthermore, increased levels of bilirubin resulted in an abnormal lipoprotein profile in PDAC patients. Additionally, we observed that the levels of a panel of metabolites (such as glucose, lactate) and lipoproteins correlated with those of inflammatory markers. Taken together, the metabolic phenotype can help distinguish PDAC severity and be used in predicting patient survival and in informing treatment intervention.

Download Full-text