A Proteomic Comparison of Formalin-Fixed Paraffin-Embedded Pancreatic Tissue from Autoimmune Pancreatitis, Chronic Pancreatitis, and Pancreatic Cancer

Paulo, João A.; Kadiyala, Vivek; Brizard, Scott; Banks, Peter A.; Steen, Hanno; Conwell, Darwin L.

doi:10.6092/1590-8577/1508

Cited by 8 publications

(1 citation statement)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Paulo et al compared PanIN lesions and PDAC FFPE samples, identifying a list of exclusive proteins for each condition. Annexin 4A, fibronectin and mucin 2 were exclusively expressed in PDAC samples [48]. Naidoo et al conducted the first study of FFPE samples comparing PDAC and lymph node metastases and found that differentially expressed proteins were mostly related to the immune system and metabolic processes [49].…”

Section: Discussionmentioning

confidence: 99%

Identification of Carcinogenesis and Tumor Progression Processes in Pancreatic Ductal Adenocarcinoma Using High-Throughput Proteomics

Trilla-Fuertes

Gámez‐Pozo

Lumbreras-Herrera

et al. 2022

Cancers

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with an overall 5-year survival rate of just 5%. A better understanding of the carcinogenesis processes and the mechanisms of the progression of PDAC is mandatory. Fifty-two PDAC patients treated with surgery and adjuvant therapy, with available primary tumors, normal tissue, preneoplastic lesions (PanIN), and/or lymph node metastases, were selected for the study. Proteins were extracted from small punches and analyzed by LC-MS/MS using data-independent acquisition. Proteomics data were analyzed using probabilistic graphical models, allowing functional characterization. Comparisons between groups were made using linear mixed models. Three proteomic tumor subtypes were defined. T1 (32% of patients) was related to adhesion, T2 (34%) had metabolic features, and T3 (34%) presented high splicing and nucleoplasm activity. These proteomics subtypes were validated in the PDAC TCGA cohort. Relevant biological processes related to carcinogenesis and tumor progression were studied in each subtype. Carcinogenesis in the T1 subtype seems to be related to an increase of adhesion and complement activation node activity, whereas tumor progression seems to be related to nucleoplasm and translation nodes. Regarding the T2 subtype, it seems that metabolism and, especially, mitochondria act as the motor of cancer development. T3 analyses point out that nucleoplasm, mitochondria and metabolism, and extracellular matrix nodes could be involved in T3 tumor carcinogenesis. The identified processes were different among proteomics subtypes, suggesting that the molecular motor of the disease is different in each subtype. These differences can have implications for the development of future tailored therapeutic approaches for each PDAC proteomics subtype.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of Carcinogenesis and Tumor Progression Processes in Pancreatic Ductal Adenocarcinoma Using High-Throughput Proteomics

Trilla-Fuertes

Gámez‐Pozo

Lumbreras-Herrera

et al. 2022

Cancers

View full text Add to dashboard Cite

show abstract

Laser Capture Microdissection of Pancreatic Acinar Cells to Identify Proteomic Alterations in a Murine Model of Caerulein-Induced Pancreatitis

Shapiro¹,

Komar²,

Hancioglu³

et al. 2017

Clinical and Translational Gastroenterology

Self Cite

View full text Add to dashboard Cite

Objectives:Chronic pancreatitis (CP) is characterized by inflammation and fibrosis of the pancreas, leading to pain, parenchymal damage, and loss of exocrine and endocrine function. There are currently no curative therapies; diagnosis remains difficult and aspects of pathogenesis remain unclear. Thus, there is a need to identify novel biomarkers to improve diagnosis and understand pathophysiology. We hypothesize that pancreatic acinar regions contain proteomic signatures relevant to disease processes, including secreted proteins that could be detected in biofluids.Methods:Acini from pancreata of mice injected with or without caerulein were collected using laser capture microdissection followed by mass spectrometry analysis. This protocol enabled high-throughput analysis that captured altered protein expression throughout the stages of CP.Results:Over 2,900 proteins were identified, whereas 331 were significantly changed ≥2-fold by mass spectrometry spectral count analysis. Consistent with pathogenesis, we observed increases in proteins related to fibrosis (e.g., collagen, P<0.001), several proteases (e.g., trypsin 1, P<0.001), and altered expression of proteins associated with diminished pancreas function (e.g., lipase, amylase, P<0.05). In comparison with proteomic data from a public data set of CP patients, a significant correlation was observed between proteomic changes in tissue from both the caerulein model and CP patients (r=0.725, P<0.001).CONCLUSIONS:This study illustrates the ability to characterize proteome changes of acinar cells isolated from pancreata of caerulein-treated mice and demonstrates a relationship between signatures from murine and human CP.

show abstract

Chemical composition and the potential for proteomic transformation in cancer, hypoxia, and hyperosmotic stress

Dick¹

2017

Preprint

View full text Add to dashboard Cite

Models of chemical composition and thermodynamic potential emphasize the microenvironmental context for proteomic transformations. Here, data from 71 comparative proteomics studies were analyzed using elemental ratios and chemical components as measures of oxidation and hydration state. Experimental lowering of oxygen availability (hypoxia) and water activity (hyperosmotic stress) are reflected in decreased oxidation and hydration states of proteomes, but up-expressed proteins in colorectal and pancreatic cancer most often have higher average oxidation or hydration state. Calculations of chemical affinity were used to quantify the thermodynamic potentials for transformation of proteomes as a function of fugacity of O 2 and activity of H 2 O, which serve as scales of oxidation and hydration potential. Potential diagrams for the overall reactions between down-and up-expressed proteins in various datasets have predicted equipotential lines that cluster near unit activity of H 2 O, suggesting that protein expression is sensitive to local variations in water activity. A redox balance calculation indicates that an increase in the lipid to protein ratio in cancer cells by 20% over hypoxic cells would generate an electron sink of sufficient size for oxidation of the cancer proteomes. These findings demonstrate consistent, condition-dependent chemical differences between proteomes, identify primary microenvironmental constraints on proteomic transformations, and help to quantify the redox balance among cellular macromolecules. The datasets and computer code used here are supplied in a new R package, canprot.

show abstract

A Proteomic Comparison of Formalin-Fixed Paraffin-Embedded Pancreatic Tissue from Autoimmune Pancreatitis, Chronic Pancreatitis, and Pancreatic Cancer

Cited by 8 publications

References 56 publications

Identification of Carcinogenesis and Tumor Progression Processes in Pancreatic Ductal Adenocarcinoma Using High-Throughput Proteomics

Identification of Carcinogenesis and Tumor Progression Processes in Pancreatic Ductal Adenocarcinoma Using High-Throughput Proteomics

Laser Capture Microdissection of Pancreatic Acinar Cells to Identify Proteomic Alterations in a Murine Model of Caerulein-Induced Pancreatitis

Chemical composition and the potential for proteomic transformation in cancer, hypoxia, and hyperosmotic stress

Contact Info

Product

Resources

About