The Role of Genetic, Metabolic, Inflammatory, and Immunologic Mediators in the Progression of Intraductal Papillary Mucinous Neoplasms to Pancreatic Adenocarcinoma

Shockley, Kylie E.; To, Briana; Chen, Wei; Lozanski, Gerard; Cruz‐Monserrate, Zobeida; Krishna, Somashekar G.

doi:10.3390/cancers15061722

Cited by 6 publications

(2 citation statements)

References 92 publications

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“…In addition, according to Shockley et al . 25 , genetic and metabolic changes, along with other disruptions to the cellular microenvironment, including immune alterations and inflammation, can contribute to tumorigenesis. Furthermore, Roth et al .…”

Section: Discussionmentioning

confidence: 99%

Impact of adjuvant therapy in patients with invasive intraductal papillary mucinous neoplasms of the pancreas: an international multicenter cohort study

Choi

Wang

Park

et al. 2023

International Journal of Surgery

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Background: Adjuvant therapy prolongs survival in patients with pancreatic ductal adenocarcinoma. However, no clear guidelines are available regarding the oncologic effects of adjuvant therapy (AT) in resected invasive intraductal papillary mucinous neoplasms (IPMN). The aim was to investigate the potential role of AT in patients with resected invasive IPMN. Materials and methods: From 2001 to 2020, 332 patients with invasive pancreatic IPMN were retrospectively reviewed in 15 centres in eight countries. Propensity score-matched and stage-matched survival analyses were conducted. Results: A total of 289 patients were enroled in the study after exclusion (neoadjuvant therapy, unresectable disease, uncertain AT status, and stage IV). A total of 170 patients were enroled in a 1:1 propensity score-matched analysis according to the covariates. In the overall cohort, disease-free survival was significantly better in the surgery alone group than in the AT group (P=0.003), but overall survival (OS) was not (P=0.579). There were no significant differences in OS in the stage-matched analysis between the surgery alone and AT groups (stage I, P=0.402; stage II, P=0.179). AT did not show a survival benefit in the subgroup analysis according to nodal metastasis (N0, P=0.481; N+, P=0.705). In multivariate analysis, node metastasis (hazard ratio, 4.083; 95% CI, 2.408−6.772, P<0.001), and cancer antigen 19-9 greater than or equal to 100 (hazard ratio, 2.058; 95% CI, 1.247−3.395, P=0.005) were identified as adverse prognostic factors in resected invasive IPMN. Conclusion: The current AT strategy may not be recommended to be performed with resected invasive IPMN in stage I and II groups, unlike pancreatic ductal adenocarcinoma. Further investigations of the potential role of AT in invasive IPMN are recommended.

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Section: Discussionmentioning

confidence: 99%

Impact of adjuvant therapy in patients with invasive intraductal papillary mucinous neoplasms of the pancreas: an international multicenter cohort study

Choi

Wang

Park

et al. 2023

International Journal of Surgery

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“…Instead, regarding IPMN, other authors described new factors that could help to diagnose this type of benign neo-formation in order to avoid its evolution into a malignant phenotype. In particular, they structured their work by dividing lowand high-risk factors and identified some potential biomarkers, including some involved in metabolic pathways, that can help to identify IPMNs that have a high risk to become cancerous [10].…”

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confidence: 99%

New Insights into Metabolic Alterations and Mitochondria Re-Arrangements in Pancreatic Adenocarcinoma

Dando,

Dalla Pozza

2023

Cancers

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A genome‐wide association study identifies eight loci associated with intraductal papillary mucinous neoplasm progression toward malignancy

Gentiluomo,

Corradi,

Apadula

et al. 2024

Cancer

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BackgroundIntraductal papillary mucinous neoplasms (IPMNs) are precursors to pancreatic cancer, but not all IPMNs progress to cancer. The objective of this study was to identify the germline genetic variants associated with IPMN clinical progression by conducting the first genome‐wide association study (GWAS) and computing a polygenic hazard score (PHS) in 338 patients with IPMN.MethodsThe study population was divided into two subsets, and a Cox analysis adjusted for sex, age, cyst size at diagnosis, and the top 10 principal components was performed. A PHS was calculated using the genotypes of common variants associated with IPMN progression identified.ResultsEight loci with significant associations (p < 5 × 10−8) were identified, and the most significant was 7q21.11‐rs117620617 (hazard ratio, 16.35; 95% confidence interval, 6.93–38.60; p = 1.80 × 10−10). All variants were associated with inflammatory processes, suggesting that alleles that predispose to an inflammatory prone phenotype may promote progression. The PHS indicated a statistically significant association (hazard ratio, 18.05; 95% confidence interval, 7.96–45.80; p = 6.18 × 10−11) with IPMN progression among individuals who had the highest number of effect alleles (fourth quartile) compared with those who had the lowest number (first quartile).ConclusionsThe current results study advance the understanding of individual predisposition to IPMN progression and underscore the potential use of genetics in the stratification of patients who have IPMN.

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The Role of Genetic, Metabolic, Inflammatory, and Immunologic Mediators in the Progression of Intraductal Papillary Mucinous Neoplasms to Pancreatic Adenocarcinoma

Cited by 6 publications

References 92 publications

Impact of adjuvant therapy in patients with invasive intraductal papillary mucinous neoplasms of the pancreas: an international multicenter cohort study

Impact of adjuvant therapy in patients with invasive intraductal papillary mucinous neoplasms of the pancreas: an international multicenter cohort study

New Insights into Metabolic Alterations and Mitochondria Re-Arrangements in Pancreatic Adenocarcinoma

A genome‐wide association study identifies eight loci associated with intraductal papillary mucinous neoplasm progression toward malignancy

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