Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE63105 | GEO | 2015/01/29
SECONDARY ACCESSION(S): PRJNA266626
REPOSITORIES: GEO
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| S-EPMC7811718 | biostudies-literature
Project description:PurposeIntraductal papillary mucinous neoplasms (IPMNs) are radiographically visible precursor lesions of pancreatic cancer. Despite standard criteria for assessing risk, only 18% of cysts are malignant at resection. Thus, a large number of patients undergo unnecessary invasive surgery for benign disease. The ability to identify IPMNs with low or high risk of transforming into invasive cancer would optimize patient selection and improve surgical decision-making. The purpose of this study was to investigate quantitative CT imaging features as markers for objective assessment of IPMN risk.MethodsThis retrospective study analyzed pancreatic cyst and parenchyma regions extracted from CT scans in 103 patients to predict IPMN risk. Patients who underwent resection between 2005 and 2015 with pathologically proven branch duct (BD)-IPMN and a preoperative CT scan were included in the study. Expert pathologists categorized IPMNs as low or high risk following resection as part of routine clinical care. We extracted new radiographically inspired features as well as standard texture features and designed prediction models for the categorization of high- and low-risk IPMNs. Five clinical variables were also combined with imaging features to design prediction models.ResultsUsing images from 103 patients and tenfold cross-validation technique, the novel radiographically inspired imaging features achieved an area under the receiver operating characteristic curve (AUC) of 0.77, demonstrating their predictive power. The combination of these features with clinical variables obtained the best performance (AUC = 0.81).ConclusionThe present study demonstrates that features extracted from pretreatment CT images can predict the risk of IPMN. Development of a preoperative model to discriminate between low-risk and high-risk IPMN will improve surgical decision-making.
| S-EPMC8050835 | biostudies-literature
Project description:Intraductal papillary mucinous neoplasms (IPMN) are precursors to infiltrating pancreatic ductal adenocarcinomas. Widespread epigenetic alterations are characteristic of many cancers, yet few studies have systematically analyzed epigenetic alterations of neoplastic precursors. Our goal was to conduct genome-wide CpG island methylation profiling to identify aberrantly methylated loci in IPMNs.We compared the CpG island methylation profiles of six IPMNs to normal primary pancreatic duct samples using methylation CpG island amplification (MCA) and Agilent CpG island microarray (MCAM) analysis. When selected 13 genes identified as differentially methylated by MCAM for methylation-specific PCR (MSP) analysis in an independent set of IPMNs and normal pancreas samples and conducted expression analysis of selected genes.We identified 2,259 loci as differentially methylated in at least one of six IPMNs including 245 genes hypermethylated in IPMNs with high-grade dysplasia compared with normal pancreatic duct samples. Eleven of 13 genes evaluated by MSP were more commonly methylated in 61 IPMNs than in 43 normal pancreas samples. Several genes (BNIP3, PTCHD2, SOX17, NXPH1, EBF3) were significantly more likely to be methylated in IPMNs with high-grade than with low-grade dysplasia. One gene, SOX17, showed loss of protein expression by immunohistochemistry in 22% (19 of 88) of IPMNs. The most specific marker, BNIP3, was not methylated in any IPMNs with low-grade dysplasia or in normal pancreas samples.IPMNs undergo extensive aberrant CpG island hypermethylation. The detection of genes selectively methylated in high-grade IPMNs such as BNIP3 may have use in the clinical evaluation of IPMNs.
| S-EPMC3271174 | biostudies-other
Project description:To examine the clinicopathologic features and clonal relationship of multifocal intraductal papillary mucinous neoplasms (IPMNs) of the pancreas.Intraductal papillary mucinous neoplasms are increasingly diagnosed cystic precursor lesions of pancreatic cancer. Intraductal papillary mucinous neoplasms can be multifocal and a potential cause of recurrence after partial pancreatectomy.Thirty four patients with histologically documented multifocal IPMNs were collected and their clinicopathologic features catalogued. In addition, thirty multifocal IPMNs arising in 13 patients from 3 hospitals were subjected to laser microdissection followed by KRAS pyrosequencing and loss of heterozygosity (LOH) analysis on chromosomes 6q and 17p. Finally, we sought to assess the clonal relationships among multifocal IPMNs.We identified 34 patients with histologically documented multifocal IPMNs. Synchronous IPMNs were present in 29 patients (85%), whereas 5 (15%) developed clinically significant metachronous IPMNs. Six patients (18%) had a history of familial pancreatic cancer. A majority of multifocal IPMNs (86% synchronous, 100% metachronous) were composed of branch duct lesions, and typically demonstrated a gastric-foveolar subtype epithelium with low or intermediate grades of dysplasia. Three synchronous IPMNs (10%) had an associated invasive cancer. Molecular analysis of multiple IPMNs from 13 patients demonstrated nonoverlapping KRAS gene mutations in 8 patients (62%) and discordant LOH profiles in 7 patients (54%); independent genetic alterations were established in 9 of the 13 patients (69%).The majority of multifocal IPMNs arise independently and exhibit a gastric-foveolar subtype, with low to intermediate dysplasia. These findings underscore the importance of life-long follow-up after resection for an IPMN.
| S-EPMC3534752 | biostudies-literature
Project description:BackgroundIntraductal papillary mucinous neoplasms (IPMNs) are the precursor lesions of pancreatic cancers, requiring active surgical intervention during cancer development. However, the current criteria for predicting malignant IPMNs remain challenging and limited. Hence, this study aimed to assess the discriminatory performance of circulating cytokines, including TNF-α, IL-2R, IL-6, and IL-8, then build a novel predictive model to improve the diagnostic accuracy.MethodA total of 131 retrospective (from March 2016 to December 2019) and 53 prospective (from March 2020 to January 2021) patients who were histologically confirmed as IPMNs were consecutively collected and analyzed.ResultThe circulating levels of TNF-α, IL-2R, IL-6, and IL-8 were significantly elevated in malignant IPMNs, and were verified as independent factors for malignant IPMNs (p < 0.05). Then, a novel score, the circulating cytokine score (CCS), was calculated and demonstrated as an independent predictive indicator with a higher area under the curve (AUC) than each cytokine alone (p < 0.001). Besides the CCS, two high-risk stigmata features, the presence of solid component (PSC), and main pancreatic duct (MPD) dilation ≥10 mm were also demonstrated as independent indicators for predicting malignant IPMNs. Finally, a novel nomogram incorporating the CCS and these two high-risk stigmata features presented a remarkable diagnostic performance, both in the training and validation cohorts with AUCs of 0.928 and 0.873, respectively.ConclusionThe CCS can be considered a novel independent predictive indicator for malignant IPMNs. Additionally, the formulated nomogram model integrating the CCS, PSC, and MPD ≥10 mm can be a valuable and promising tool for predicting the malignant transformation of IPMNs during long-term follow-ups to assist in timely and accurate surgical decisions.
| S-EPMC9972143 | biostudies-literature
Project description:Intraductal papillary mucinous neoplasm (IPMN) is a common pancreatic cystic neoplasm that is often invasive and metastatic, resulting in a poor prognosis. Few molecular alterations unique to IPMN are known. We performed whole-exome sequencing for a primary IPMN tissue, which uncovered somatic mutations in KCNF1, DYNC1H1, PGCP, STAB1, PTPRM, PRPF8, RNASE3, SPHKAP, MLXIPL, VPS13C, PRCC, GNAS, KRAS, RBM10, RNF43, DOCK2, and CENPF. We further analyzed GNAS mutations in archival cases of 118 IPMNs and 32 pancreatic ductal adenocarcinomas (PDAs), which revealed that 48 (40.7%) of the 118 IPMNs but none of the 32 PDAs harbored GNAS mutations. G-protein alpha-subunit encoded by GNAS and its downstream targets, phosphorylated substrates of protein kinase A, were evidently expressed in IPMN; the latter was associated with neoplastic grade. These results indicate that GNAS mutations are common and specific for IPMN, and activation of G-protein signaling appears to play a pivotal role in IPMN.
| S-EPMC3240977 | biostudies-literature
Project description:Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal cancers worldwide, partly because methods are lacking to detect disease at an early, operable stage. Noninvasive PDAC precursors called intraductal papillary mucinous neoplasms (IPMN) exist, and strategies are needed to aid in their proper diagnosis and management. Data support the importance of miRNAs in the progression of IPMNs to malignancy, and we hypothesized that miRNAs may be shed from IPMN tissues and detected in blood. Our primary goals were to measure the abundance of miRNAs in archived preoperative plasma from individuals with pathologically confirmed IPMNs and healthy controls and discover plasma miRNAs that distinguish between IPMN patients and controls and between "malignant" and "benign" IPMNs. Using novel nCounter technology to evaluate 800 miRNAs, we showed that a 30-miRNA signature distinguished 42 IPMN cases from 24 controls [area underneath the curve (AUC) = 74.4; 95% confidence interval (CI), 62.3-86.5, P = 0.002]. The signature contained novel miRNAs and miRNAs previously implicated in pancreatic carcinogenesis that had 2- to 4-fold higher expression in cases than controls. We also generated a 5-miRNA signature that discriminated between 21 malignant (high-grade dysplasia and invasive carcinoma) and 21 benign (low- and moderate-grade dysplasia) IPMNs (AUC = 73.2; 95% CI, 57.6-73.2, P = 0.005), and showed that paired plasma and tissue samples from patients with IPMNs can have distinct miRNA expression profiles. This study suggests feasibility of using new cost-effective technology to develop a miRNA-based blood test to aid in the preoperative identification of malignant IPMNs that warrant resection while sparing individuals with benign IPMNs the morbidity associated with overtreatment.
| S-EPMC4560649 | biostudies-literature
Project description:Pancreatic ductal adenocarcinoma (PDA) has a 5-year survival rate of less than 5% and is the sixth leading cause of cancer death. Although KRAS mutations are one of the major driver mutations in PDA, KRAS mutation alone is not sufficient to induce invasive pancreatic cancer in mice model. HER2, also known as ERBB2, is a receptor tyrosine kinase, and overexpression of HER2 is associated with poor clinical outcomes in pancreatic cancer. However, no report has shown whether HER2 and its downstream signaling contributes to the pancreatic cancer development. By immunohistochemical analysis in human cases, HER2 protein expression was detected in 40% of PDAs and 29% of intraductal papillary mucinous carcinomas, another type of pancreatic cancer. In a mouse model, we showed overexpression of activated HER2 (HER2 NT ) in the pancreas, in which cystic neoplastic lesions resembling intraductal papillary mucinous neoplasm-like lesions in humans had developed. We also found that HER2 NT cooperated with oncogenic Kras to accelerate the development of pancreatic intraepithelial neoplasms. In addition, using pancreatic organoids in 3D cultures, we found that organoids cultured from HER2 NT /Kras double transgenic mice showed proliferative potential and tumorigenic ability cooperatively. HER2-signaling inhibition was suggested to be an new therapeutic target in some types of PDAs.
| S-EPMC5906617 | biostudies-literature