The Relationship between Acute and Chronic Pancreatitis with Pancreatic Adenocarcinoma: Review

Alhobayb, Tamara Y.; Peravali, Rahul; Ashkar, Motaz

doi:10.3390/diseases9040093

Cited by 15 publications

(13 citation statements)

References 85 publications

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“…Interestingly, CP shows an intermediate enrichment for ADAM9, AKT2, KRAS, S100A6 and S100P between PDAC and normal pancreas and thereby supports the hypothesis of CP being a preliminary stage to PDAC (Alhobayb et al, 2021; Del Poggetto et al, 2021; Vujasinovic et al, 2020). However, the receptor tyrosine kinase ERBB2 was not detected in CP and thereby showed an even diminished detection compared to normal pancreas samples.…”

Section: Resultssupporting

confidence: 71%

“…Challenges in the early detection of pancreatic cancer further include identifying at-risk individuals among the general population who would particularly benefit from diagnostic biomarkers for PDAC (Singhi, Koay, Chari, & Maitra, 2019). One of these major risk factors for the development of PDAC represents chronic pancreatitis (CP), which is characterized by recurrent, highly inflammatory episodes in the pancreatic tissue and has been discussed to be a preliminary stage to PDAC (Alhobayb, Peravali, & Ashkar, 2021; Del Poggetto et al, 2021; Vujasinovic et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Targeted and Explorative Profiling of Kallikrein Proteases and Global Proteome Biology of Pancreatic Ductal Adenocarcinoma, Chronic Pancreatitis, and Normal Pancreas Highlights Disease-Specific Proteome Remodelling

Werner

Bernhard

Cosenza-Contreras

et al. 2022

Preprint

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Pancreatic ductal adenocarcinoma (PDAC) represents one of the most aggressive and lethal malignancies worldwide with an urgent need for new diagnostic and therapeutic strategies. One major risk factor for PDAC is the pre-indication of chronic pancreatitis (CP), which represents highly inflammatory pancreatic tissue. Kallikreins (KLKs) are secreted serine proteases that play an important role in various cancers as components of the tumor microenvironment. Previous studies of KLKs in solid tumors largely relied on either transcriptomics or immunodetection. We present one of the first targeted mass spectrometry profiling of kallikrein proteases in PDAC, CP, and normal pancreas. We show that KLK6 and KLK10 are significantly upregulated in PDAC (n=14) but not in CP (n=7) when compared to normal pancreas (n=21), highlighting their specific intertwining with malignancy. Additional explorative proteome profiling identified 5936 proteins in our pancreatic cohort and observed disease-specific proteome rearrangements in PDAC and CP. As such, PDAC features an enriched proteome motif for extracellular matrix (ECM) and cell adhesion while there is depletion of mitochondrial energy metabolism proteins, reminiscent of the Warburg effect. Although often regarded as a PDAC hallmark, the ECM fingerprint was also observed in CP, alongside with a prototypical inflammatory proteome motif as well as with an increased wound healing process and proteolytic activity, thereby possibly illustrating tissue autolysis. Proteogenomic analysis based on publicly accessible data sources identified 112 PDAC-specific and 32 CP-specific single amino acid variants, which among others affect KRAS and ANKHD1. Our study emphasizes the diagnostic potential of kallikreins and provides novel insights into proteomic characteristics of PDAC and CP.

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Section: Resultssupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Targeted and Explorative Profiling of Kallikrein Proteases and Global Proteome Biology of Pancreatic Ductal Adenocarcinoma, Chronic Pancreatitis, and Normal Pancreas Highlights Disease-Specific Proteome Remodelling

Werner

Bernhard

Cosenza-Contreras

et al. 2022

Preprint

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“…When a Kras mutation is combined with experimentally induced inflammation, mice rapidly develop precancerous pancreatic intraepithelial neoplasia (PanIN) lesions and PDAC ( Guerra et al, 2007 ). Although there is no reported clinical association between pancreatitis and PanNETs, there are associations between chronic inflammation and PDAC ( Hausmann et al, 2014 ; Alhobayb et al, 2021 ). Moreover, the microenvironment can strongly influence tumorigenesis.…”

Section: Resultsmentioning

confidence: 99%

Context matters – Daxx and Atrx are not robust tumor suppressors in the murine endocrine pancreas

Sun

Estrella

Whitley

et al. 2022

Disease Models &Amp; Mechanisms

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Genome sequencing has revealed the importance of epigenetic regulators in tumorigenesis. The genes encoding the chromatin remodeling complex DAXX:ATRX are frequently mutated in pancreatic neuroendocrine tumors (PanNETs); however, the underlying mechanisms of how mutations contribute to tumorigenesis are only partially understood, in part because of the lack of relevant pre-clinical models. Here we used genetically engineered mouse models combined with environmental stress to evaluate the tumor suppressor functions of Daxx and Atrx in the mouse pancreas. Daxx or Atrx loss, alone or in combination with Men1 loss, do not drive nor accelerate pancreatic neuroendocrine tumorigenesis. Moreover, Daxx loss does not cooperate with environmental stresses (ionizing radiation or pancreatitis) or with the loss of other tumor suppressors (Pten or p53) to promote pancreatic neuroendocrine tumorigenesis. However, due to promiscuity of the Cre promoter used, hepatocellular carcinomas (HCC) and osteosarcomas were observed in some instances. Overall, our findings suggest that Daxx and Atrx are not robust tumor suppressors in the endocrine pancreas of mice and indicate the context of a human genome is essential for tumorigenesis.

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“…In conclusion, inflammation is involved in the entire gastrointestinal tumor process. The worse inflammation is mainly chronic inflammation, which can be induced by many reasons, such as unhealthy high-fat diet, excessive use of antibiotics, imbalance of intestinal flora and so on[ 16 ]. Majumder et al [ 1 ] systematically summarized the role of inflammatory factors in colon cancer.…”

Section: To the Editormentioning

confidence: 99%

Acute or chronic inflammation role in gastrointestinal oncology

Chen¹,

Liang²,

Chen³

et al. 2022

WJGO

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The Relationship between Acute and Chronic Pancreatitis with Pancreatic Adenocarcinoma: Review

Cited by 15 publications

References 85 publications

Targeted and Explorative Profiling of Kallikrein Proteases and Global Proteome Biology of Pancreatic Ductal Adenocarcinoma, Chronic Pancreatitis, and Normal Pancreas Highlights Disease-Specific Proteome Remodelling

Targeted and Explorative Profiling of Kallikrein Proteases and Global Proteome Biology of Pancreatic Ductal Adenocarcinoma, Chronic Pancreatitis, and Normal Pancreas Highlights Disease-Specific Proteome Remodelling

Context matters – Daxx and Atrx are not robust tumor suppressors in the murine endocrine pancreas

Acute or chronic inflammation role in gastrointestinal oncology

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