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Gene expression analysis of pancreatic cystic neoplasm in SV40Tag transgenic mice model.

ABSTRACT: AIM:To study the gene expression changes in pancreatic cystic neoplasm in SV40Tag transgenic mice model and to provide information about the prevention, clinical diagnosis and therapy of pancreatic cancer. METHODS:Using the pBC-SV40Tag transgenic mice model of pancreatic cystic neoplasm, we studied the gene expression changes by applying high-density microarrays. Validation of part gene expression profiling data was performed using real-time PCR. RESULTS:By using high-density oligonucleotide microarray, of 14113 genes, 453 were increased and 760 decreased in pancreatic cystic neoplasm, including oncogenes, cell-cycle-related genes, signal transduction-related genes, skeleton-related genes and metabolism-related genes. Among these, we confirmed the changes in Igf, Shh and Wnt signal pathways with real-time PCR. The results of real-time PCR showed similar expression changes in gene chip. CONCLUSION:all the altered expression genes are associated with cell cycle, DNA damage and repair, signal pathway, and metabolism. SV40Tag may cooperate with several proteins in promoting tumorigenesis.

SUBMITTER: Feng J

PROVIDER: S-EPMC4146848 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature

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Gene expression analysis of pancreatic cystic neoplasm in SV40Tag transgenic mice model.

Feng Jie J Sun Qiang Q Gao Cheng C Dong Juan J Wei Xiao-Luan XL Xing Hua H Li Hou-Da HD

World journal of gastroenterology 20070401 15

<h4>Aim</h4>To study the gene expression changes in pancreatic cystic neoplasm in SV40Tag transgenic mice model and to provide information about the prevention, clinical diagnosis and therapy of pancreatic cancer.<h4>Methods</h4>Using the pBC-SV40Tag transgenic mice model of pancreatic cystic neoplasm, we studied the gene expression changes by applying high-density microarrays. Validation of part gene expression profiling data was performed using real-time PCR.<h4>Results</h4>By using high-densi ...[more]

PMID: 17465505

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Project description:BackgroundCystic pancreatic lesions consist of a wide variety of lesions that are becoming increasingly diagnosed with the growing use of imaging techniques. Of these, mucinous cysts are especially relevant due to their risk of malignancy. However, morphological findings are often suboptimal for their differentiation. Endoscopic ultrasound fine-needle aspiration (EUS-FNA) with molecular analysis has been suggested to improve the diagnosis of pancreatic cysts.AimTo determine the impact of molecular analysis on the detection of mucinous cysts and malignancy.MethodsAn 18-month prospective observational study of consecutive patients with pancreatic cystic lesions and an indication for EUS-FNA following European clinical practice guidelines was conducted. These cysts included those > 15 mm with unclear diagnosis, and a change in follow-up or with concerning features in which results might change clinical management. EUS-FNA with cytological, biochemical and glucose and molecular analyses with next-generation sequencing were performed in 36 pancreatic cysts. The cysts were classified as mucinous and non-mucinous by the combination of morphological, cytological and biochemical analyses when surgery was not performed. Malignancy was defined as cytology positive for malignancy, high-grade dysplasia or invasive carcinoma on surgical specimen, clinical or morphological progression, metastasis or death related to neoplastic complications during the 6-mo follow-up period. Next-generation sequencing results were compared for cyst type and malignancy.ResultsOf the 36 lesions included, 28 (82.4%) were classified as mucinous and 6 (17.6%) as non-mucinous. Furthermore, 5 (13.9%) lesions were classified as malignant. The amount of deoxyribonucleic acid obtained was sufficient for molecular analysis in 25 (69.4%) pancreatic cysts. The amount of intracystic deoxyribonucleic acid was not statistically related to the cyst fluid volume obtained from the lesions. Analysis of KRAS and/or GNAS showed 83.33% [95% confidence interval (CI): 63.34-100] sensitivity, 60% (95%CI: 7.06-100) specificity, 88.24% (95%CI: 69.98-100) positive predictive value and 50% (95%CI: 1.66-98.34) negative predictive value (P = 0.086) for the diagnosis of mucinous cystic lesions. Mutations in KRAS and GNAS were found in 2/5 (40%) of the lesions classified as non-mucinous, thus recategorizing those lesions as mucinous neoplasms, which would have led to a modification of the follow-up plan in 8% of the cysts in which molecular analysis was successfully performed. All 4 (100%) malignant cysts in which molecular analysis could be performed had mutations in KRAS and/or GNAS, although they were not related to malignancy (P > 0.05). None of the other mutations analyzed could detect mucinous or malignant cysts with statistical significance (P > 0.05).ConclusionMolecular analysis can improve the classification of pancreatic cysts as mucinous or non-mucinous. Mutations were not able to detect malignant lesions.

Project description:PurposeThis study aimed to develop and verify a multi-phase (MP) computed tomography (CT)-based radiomics nomogram to differentiate pancreatic serous cystic neoplasms (SCNs) from mucinous cystic neoplasms (MCNs), and to compare the diagnostic efficacy of radiomics models for different phases of CT scans.Materials and methodsA total of 170 patients who underwent surgical resection between January 2011 and December 2018, with pathologically confirmed pancreatic cystic neoplasms (SCN=115, MCN=55) were included in this single-center retrospective study. Radiomics features were extracted from plain scan (PS), arterial phase (AP), and venous phase (VP) CT scans. Algorithms were performed to identify the optimal features to build a radiomics signature (Radscore) for each phase. All features from these three phases were analyzed to develop the MP-Radscore. A combined model comprised the MP-Radscore and imaging features from which a nomogram was developed. The accuracy of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration tests, and decision curve analysis.ResultsFor each scan phase, 1218 features were extracted, and the optimal ones were selected to construct the PS-Radscore (11 features), AP-Radscore (11 features), and VP-Radscore (12 features). The MP-Radscore (14 features) achieved better performance based on ROC curve analysis than any single phase did [area under the curve (AUC), training cohort: MP-Radscore 0.89, PS-Radscore 0.78, AP-Radscore 0.83, VP-Radscore 0.85; validation cohort: MP-Radscore 0.88, PS-Radscore 0.77, AP-Radscore 0.83, VP-Radscore 0.84]. The combination nomogram performance was excellent, surpassing those of all other nomograms in both the training cohort (AUC, 0.91) and validation cohort (AUC, 0.90). The nomogram also performed well in the calibration and decision curve analyses.ConclusionsRadiomics for arterial and venous single-phase models outperformed the plain scan model. The combination nomogram that incorporated the MP-Radscore, tumor location, and cystic number had the best discriminatory performance and showed excellent accuracy for differentiating SCN from MCN.

Project description:BackgroundSerous cystic neoplasm (SCN), mucinous cystic neoplasm (MCN), and intraductal papillary mucinous neoplasm (IPMN) comprise a large proportion of pancreatic cystic neoplasms (PCNs). Patients with MCN and IPMN require surgery due to the potential of malignant transformation, whereas those with SCN require periodic surveillance. However, the differential diagnosis of patients with PCNs before treatment remains a great challenge for all surgeons. Therefore, the establishment of a reliable diagnostic tool is urgently required for the improvement of precision diagnostics.MethodsBetween February 2015 and December 2020, 143 consecutive patients with PCNs who were confirmed by postoperative pathology were retrospectively included in the study cohort, then randomized into development and test cohorts at a ratio of 7:3. The predictors of preoperative clinical-radiologic parameters were evaluated by univariate and multivariable logistic regression analyses. A total of 1,218 radiomics features were computationally extracted from the enhanced computed tomography (CT) scans of the tumor region, and a radiomics signature was established by the random forest algorithm. In the development cohort, multi- and binary-class radiomics models integrating preoperative variables and radiomics features were constructed to distinguish between the 3 types of PCNs. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to evaluate the predictive efficiency of the model. An independent internal test cohort was applied to validate the classification models.ResultsAll preoperative prediction models were built by integrating the radiomics signature with 13 diagnosis-related radiomics features and 3 important clinical-radiologic parameters: age, sex, and tumor diameter. The multiclass prediction model presented an overall accuracy of 0.804 in the development cohort and 0.707 in the test cohort. The binary-class prediction models displayed higher overall accuracies of 0.853, 0.866, and 0.928 in the development dataset and 0.750, 0.839, and 0.889 in the test dataset. In the test cohort, the binary-class radiomics models showed better predictive performances {AUC =0.914 [95% confidence interval (CI): 0.786 to 1.000], 0.863 (95% CI: 0.714 to 0.941), and 0.926 (95% CI: 0.824 to 1.000)} than the multiclass radiomics model [AUC =0.850 (95% CI: 0.696 to 1.000)], with a large net benefit in the decision curve analysis (DCA). The radiomics-based nomogram provided the correct predicted probability for the diagnosis of PCNs.ConclusionsThe proposed radiomics models with clinical-radiologic parameters and radiomics features help to predict the accurate diagnosis among PCNs to advance personalized medicine.

Dataset Information

Gene expression analysis of pancreatic cystic neoplasm in SV40Tag transgenic mice model.

Publications

Gene expression analysis of pancreatic cystic neoplasm in SV40Tag transgenic mice model.

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