Association Between Clinical Backgrounds and Malignant Progression of Suspected Intraductal Papillary Mucinous Neoplasm

Fukushima, Genki; Abe, Kodai; Kitago, Minoru; Iwasaki, Eisuke; Hirata, Aya; Takemura, Ryo; Ishii, Ryota; Yagi, Hiroshi; Abe, Yuta; Hasegawa, Yasushi; Fukuhara, Seiichiro; Hori, Shutaro; Tanaka, Masayuki; Nakano, Yuichi; Yokose, Takahiro; Shimane, Gaku; Kitagawa, Yuko

doi:10.1097/mpa.0000000000002064

Cited by 4 publications

(2 citation statements)

References 32 publications

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“…reported that smoking may accelerate the development of IPMN and the subsequent transformation into invasive cancer ( 64 ). The role of smoking was also reported in a Japanese population, in agreement with our observation in Europeans ( 65 ). In pancreatic cancer, the molecular mechanisms of cigarette smoking are currently unknown; however, a synergic role of nicotine metabolites and rare mutations (i.e., KRAS mutations) has been proposed.…”

Section: Discussionsupporting

confidence: 92%

Role of pancreatic ductal adenocarcinoma risk factors in intraductal papillary mucinous neoplasm progression

et al. 2023

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IntroductionPancreatic ductal adenocarcinoma (PDAC) is lethal due to its late diagnosis and lack of successful treatments. A possible strategy to reduce its death burden is prevention. Intraductal papillary mucinous neoplasms (IPMNs) are precursors of PDAC. It is difficult to estimate the incidence of IPMNs because they are asymptomatic. Two recent studies reported pancreatic cysts in 3% and 13% of scanned subjects. The possibility of identifying a subgroup of IPMN patients with a higher probability of progression into cancer could be instrumental in increasing the survival rate. In this study, genetic and non-genetic PDAC risk factors were tested in a group of IPMN patients under surveillance.MethodsA retrospective study was conducted on 354 IPMN patients enrolled in two Italian centres with an average follow-up of 64 months. With the use of DNA extracted from blood, collected at IPMN diagnosis, all patients were genotyped for 30 known PDAC risk loci. The polymorphisms were analysed individually and grouped in an unweighted polygenic score (PGS) in relation to IPMN progression. The ABO blood group and non-genetic PDAC risk factors were also analysed. IPMN progression was defined based on the development of worrisome features and/or high-risk stigmata during follow-up.ResultsTwo genetic variants (rs1517037 and rs10094872) showed suggestive associations with an increment of IPMN progression. After correction for multiple testing, using the Bonferroni correction, none of the variants showed a statistically significant association. However, associations were observed for the non-genetic variables, such as smoking status, comparing heavy smokers with light smokers (HR = 3.81, 95% 1.43–10.09, p = 0.007), and obesity (HR = 2.46, 95% CI 1.22–4.95, p = 0.012).ConclusionIn conclusion, this study is the first attempt to investigate the presence of shared genetic background between PDAC risk and IPMN progression; however, the results suggest that the 30 established PDAC susceptibility polymorphisms are not associated with clinical IPMN progression in a sample of 354 patients. However, we observed indications of cigarette smoking and body mass index (BMI) involvement in IPMN progression. The biological mechanism that could link these two risk factors to progression could be chronic inflammation, of which both smoking and obesity are strong promoters.

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Section: Discussionsupporting

confidence: 92%

Role of pancreatic ductal adenocarcinoma risk factors in intraductal papillary mucinous neoplasm progression

et al. 2023

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“…Limited and delayed diagnostic strategies increase the difficulty of diagnosis, thus severely impeding various therapeutic options. Although increasing evidence suggests that pancreatic cancer is linked to several variables, such as smoking, alcohol consumption, coffee intake, a high-fat and protein diet, and genetic background (3)(4)(5), the causes of pancreatic cancer remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Systematic analysis of expression profiles and prognostic significance of the FGF gene family in pancreatic adenocarcinoma

et al. 2022

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Pancreatic adenocarcinoma (PAAD) is a malignant tumor with one of the highest associated mortality rates worldwide, and a 5-year survival rate of <5%. Fibroblast growth factors (FGFs) serve important roles in numerous cellular functions, and dysregulation of FGFs contributes to various cancer types. However, there are few reports on the function of FGFs in PAAD. The Assistant for Clinical Bioinformatics database, Gene Expression Profiling Interactive Analysis, Kaplan-Meier plotter and Tumor Immune Estimation Resource were utilized to perform the protein-protein interaction network, functional enrichment, univariate Cox regression, least absolute shrinkage and selection operator (LASSO) Cox, differential expression, prognostic value and immune cell infiltration analyses of FGFs in patients with PAAD. Immunohistochemistry (IHC) was used to verify the predictive value of the model. A total of 22 FGF genes were identified. Based on the results of LASSO Cox regression analysis, a total of six genes, including FGF2, FGF8, FGF9, FGF13, FGF17 and FGF22, were selected for the establishment of the prognostic gene signature. High transcriptional levels of FGF17 and FGF22 were significantly associated with long overall survival. The expression of FGFs was associated with the infiltration of various immune cells. According to univariate and multivariate analyses, FGF2 and FGF8 may be useful independent prognostic biomarkers for the prognosis of patients with PAAD. IHC demonstrated that FGF2 and FGF8 were more highly expressed in PAAD tissues compared with that in normal tissues. The present findings offer a novel understanding for the selection of FGF prognostic biomarkers in PAAD.

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Association of Smoking with progression from low-risk to high-risk intraductal papillary mucinous neoplasms and pancreatic cancer

Lauri,

Apadula,

Archibugi

et al. 2025

Digestive and Liver Disease

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Association Between Clinical Backgrounds and Malignant Progression of Suspected Intraductal Papillary Mucinous Neoplasm

Cited by 4 publications

References 32 publications

Role of pancreatic ductal adenocarcinoma risk factors in intraductal papillary mucinous neoplasm progression

Role of pancreatic ductal adenocarcinoma risk factors in intraductal papillary mucinous neoplasm progression

Systematic analysis of expression profiles and prognostic significance of the FGF gene family in pancreatic adenocarcinoma

Association of Smoking with progression from low-risk to high-risk intraductal papillary mucinous neoplasms and pancreatic cancer

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