Dataset Information

Clonality analysis of neuroendocrine cells in gastric adenocarcinoma.

ABSTRACT: To achieve a better understanding of the origination of neuroendocrine (NE) cells in gastric adenocarcinoma.In this study, 120 cases of gastric adenocarcinoma were obtained. First, frozen section-immunohistochemistrical samples were selected from a large quantity of neuroendocrine cells. Second, laser capture microdissection was used to get target cells from gastric adenocarcinoma and whole genome amplification was applied to get a large quantity of DNA for further study. Third, genome-wide microsatellite abnormalities [microsatellite instability (MSI), loss of heterozygosity (LOH)] and p53 mutation were detected by polymerase chain reaction (PCR)-single-strand conformation polymer- phism-silver staining and PCR-sequencing in order to identify the clonality of NE cells.The total incidence rate of MSI was 27.4%, while LOH was 17.9%. Ten cases had a highest concordance for the two types of cells. The other samples had similar microsatellite changes, except for cases 7 and 10. Concordant p53 mutations exhibited in sample 4, 14, 21 and 27, and there were different mutations between two kinds of cells in case 7. In case 17, mutation took place only in adenocarcinoma cells. p53 mutation was closely related with degree of differentiation, tumor-node-metastasis stage, vessel invasion and lymph node metastasis. In brief, NE and adenocarcinoma cells showed the same MSI, LOH or p53 mutation in most cases (27/30). In the other three cases, different MSI, LOH or p53 mutation occurred.NE and the gastric adenocarcinoma cells may mainly derive from the same stem cells, but the remaining cases showing different origin needs further investigation.

SUBMITTER: Wang LL

PROVIDER: S-EPMC3752570 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Clonality analysis of neuroendocrine cells in gastric adenocarcinoma.

Wang Ling-Ling LL Yao Gen-You GY Zhao Zhong-Sheng ZS Wei Xiao-Li XL Xu Ru-Jun RJ

World journal of gastroenterology 20130801 32

<h4>Aim</h4>To achieve a better understanding of the origination of neuroendocrine (NE) cells in gastric adenocarcinoma.<h4>Methods</h4>In this study, 120 cases of gastric adenocarcinoma were obtained. First, frozen section-immunohistochemistrical samples were selected from a large quantity of neuroendocrine cells. Second, laser capture microdissection was used to get target cells from gastric adenocarcinoma and whole genome amplification was applied to get a large quantity of DNA for further st ...[more]

PMID: 23983439

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Project description:BackgroundPulmonary adenocarcinoma with neuroendocrine differentiation (ADE_ned) is a relatively uncommon pathological classification, and there exists considerable debate regarding its prognosis and treatment. The purpose of this study was to analyze the survival difference between patients with neuroendocrine carcinoma (NEC), adenocarcinoma (ADE), or ADE_ned and to investigate the prognostic factors influencing the outcomes of individuals diagnosed with pulmonary ADE_ned.MethodsWe retrieved information on 316 cases of ADE_ned, 188,823 cases of ADE, and 71,154 cases of NEC diagnosed between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. To account for potential confounding variables, propensity score matching (PSM) was employed. Comparative analyses were conducted to estimate the overall survival (OS) and cancer-specific survival (CSS). Finally, the Cox regression models were used to identify prognostic factors associated with pulmonary ADE_ned.ResultsPrior to PSM, patients with lung ADE_ned had a worse OS rate than did those with lung ADE or NEC (5-year OS rate: 13.3% vs. 26.6% vs. 15.6%; P<0.001 and P=0.009, respectively). In terms of CSS, the 5-year CSS rate of patients with ADE_ned was superior to that of NEC but inferior to that of ADE (28.7% vs. 26.8% vs. 43.8%; P=0.006 and P<0.001, respectively). Following PSM, the 5-year survival rate of patients with ADE_ned remained lower than that of individuals with ADE or NEC in terms of OS (13.3% vs. 24.4% vs. 23.0%; P<0.001 and P<0001, respectively) and CSS (28.8% vs. 58.6% vs. 43.1%; P<0.001 and P=0.006, respectively). Finally, the results of the competitive risk regression analysis demonstrated that several variables, including sex, T stage, N stage, M stage, and surgery, were found to be independent prognostic factors for patients diagnosed with pulmonary ADE_ned (all P values <0.05).ConclusionsPatients with lung ADE_ned had a significantly poorer survival outcome compared to those with lung ADE or NEC. Furthermore, sex, tumor-node-metastasis (TNM) stage, and surgery were found to be independent prognostic indicators for cases with lung ADE_ned.

Project description:BACKGROUND:Gastric neoplasms containing neuroendocrine carcinoma (NEC) components are rare malignancies with highly aggressive behavior and a poor prognosis and include pure NEC and mixed tumors containing NEC components. We aimed to investigate whether there is a distinct difference in overall survival (OS) between gastric neoplasms containing NEC components and gastric adenocarcinoma. METHODS:Surgically resected gastric neoplasms containing NEC components (n?=?180) and gastric adenocarcinomas (n?=?785) from January 2013 to December 2019 at Peking University Cancer Hospital were retrospectively analysed. Patients were categorized into a surgical group and a neoadjuvant group and adjusted using propensity score matching. In the two groups, gastric neoplasms containing NEC components were divided into pure NEC and mixed tumors with less than 30% (<?30% G-HMiNEN), between 30 and 70% (G-HMiNEN) and more than 70% (>?70% G-HMiNEN) neuroendocrine carcinoma components. OS was compared between these groups and the gastric adenocarcinoma group. RESULTS:The OS of gastric neoplasms containing neuroendocrine NEC components was poorer than that of gastric adenocarcinomas in the surgical group, regardless of whether the percentage of neuroendocrine cancer components was less than 30%, between 30 and 70%, more than 70% or 100%. Cox multivariable regression analysis suggested that tumor category (neoplasms containing NEC components or gastric adenocarcinoma) was an independent risk factor for prognosis. Interestingly, among patients receiving neoadjuvant therapy, the difference was not significant. CONCLUSIONS:Gastric neoplasms containing any proportion of NEC components had poorer overall survival than gastric adenocarcinoma in patients treated with surgery directly, indicating that these neoplasms are more malignant than gastric adenocarcinoma. Among the patients receiving neoadjuvant therapy, the difference in overall survival was not significant, which was in sharp contrast with the results of the surgery group, suggesting that neoadjuvant therapy may have a good effect in the treatment of these neoplasms.

Project description:In the present study, gene expression profiles were analyzed to identify the molecular mechanisms underlying gastric cardia adenocarcinoma (GCA) and gastric non-cardia adenocarcinoma (GNCA). A gene expression dataset (accession number GSE29272) was downloaded from Gene Expression Omnibus, and consisted of 62 GCA samples and 62 normal controls, as well as 72 GNCA samples and 72 normal controls. The two groups of differentially-expressed genes (DEGs) were compared to obtain common and unique DEGs. A differential analysis was performed using the Linear Models for Microarray Data package in R. Functional enrichment analysis was conducted for the DEGs using the Database for Annotation, Visualization and Integrated Discovery. Protein-protein interaction (PPI) networks were constructed for the DEGs with information from the Search Tool for the Retrieval of Interacting Genes. Subnetworks were extracted from the whole network with Cytoscape. Compared with the control, 284 and 268 genes were differentially-expressed in GCA and GNCA, respectively, of which 194 DEGs were common between GCA and GNCA. Common DEGs [e.g., claudin (CLDN)7, CLDN4 and CLDN3] were associated with cell adhesion and digestion. GCA-unique DEGs [e.g., MAD1 mitotic arrest deficient like 1, cyclin (CCN)B1, CCNB2 and CCNE1] were associated with the cell cycle and the regulation of cell proliferation, while GNCA-unique DEGs (e.g., GATA binding protein 6 and hyaluronoglucosaminidase 1) were implicated in cell death. A PPI network with 141 nodes and 446 edges were obtained, from which two subnetworks were extracted. Genes [e.g., fibronectin 1, collagen type I ?2 chain (COL1A2) and COL1A1] from the two subnetworks were implicated in extracellular matrix organization. These common DEGs could advance our understanding of the etiology of gastric cancer, while the unique DEGs in GCA and GNCA could better define the properties of specific cancers and provide potential biomarkers for diagnosis, prognosis or therapy.

Project description:ImportanceGastric neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma are rare pathological types of gastric cancer, and there is a lack of multicenter studies comparing the prognosis and recurrence patterns of gastric neuroendocrine carcinoma, gastric mixed adenoneuroendocrine carcinoma, and gastric adenocarcinoma.ObjectiveTo compare the differences in long-term survival and patterns of recurrence among gastric neuroendocrine carcinoma, gastric mixed adenoneuroendocrine carcinoma, and gastric adenocarcinoma.Design, setting, and participantsThis cohort study included patients with resectable gastric neuroendocrine carcinoma and gastric mixed adenoneuroendocrine carcinoma at 23 hospitals in China from January 2006 to December 2016. In addition, patients with gastric adenocarcinoma were selected as controls. Propensity score-matched analysis was used to match pathological stage among the different pathological types, and disease-free survival (DFS), postrecurrence survival (PRS), and patterns of recurrence were examined. Data analysis was conducted from July 15, 2020, to October 21, 2020.ExposuresCurative resection for gastric neuroendocrine carcinoma, gastric mixed adenoneuroendocrine carcinoma, and gastric adenocarcinoma.Main outcomes and measuresThe main outcomes were DFS and patterns of recurrence.ResultsA total of 3689 patients were analyzed (median [interquartile range] age, 62 [55-69] years; 2748 [74.5%] men), including 503 patients (13.6%) with gastric neuroendocrine carcinoma, 401 patients (10.9%) with gastric mixed adenoneuroendocrine carcinoma, and 2785 patients (75.5%) with gastric adenocarcinoma. After propensity score matching, 5-year DFS was 47.6% (95% CI, 42.7%-52.5%) for patients with gastric neuroendocrine carcinoma, compared with 57.6% (95% CI, 55.1%-60.1%) with gastric adenocarcinoma (P < .001) and 51.1% (95% CI, 46.0%-56.2%) for patients with gastric mixed adenoneuroendocrine carcinoma, compared with 57.8% (95% CI, 55.1%-60.5%) patients with gastric adenocarcinoma (P = .02). Multivariable analyses found that, compared with gastric adenocarcinoma, gastric neuroendocrine carcinoma (hazard ratio [HR], 1.64; 95% CI, 1.40-1.93) and gastric mixed adenoneuroendocrine carcinoma (HR, 1.25; 95% CI, 1.05-1.49) were independent risk factors associated with worse DFS. Compared with matched patients with gastric adenocarcinoma, patients with gastric neuroendocrine carcinoma were more likely to have distant recurrence (268 patients [17.2%] vs 101 patients [23.7%]; P = .002), as were patients with gastric mixed adenoneuroendocrine carcinoma (232 patients [17.3%] vs 76 patients [22.8%]; P = .02). In multivariate analysis, gastric neuroendocrine carcinoma (HR, 2.22; 95% CI, 1.66-2.98) and gastric mixed adenoneuroendocrine carcinoma (HR, 1.70; 95% CI, 1.24-2.34) were independent risk factors associated with distant recurrence. Additionally, T3 to T4 stage (odds ratio, 2.84; 95% CI, 1.57-5.14; P = .001) and lymph node metastasis (odds ratio, 2.01; 95% CI, 1.31-3.10; P = .002) were independent risk factors associated with distant recurrence of gastric neuroendocrine carcinoma and gastric mixed adenoneuroendocrine carcinoma.Conclusions and relevanceThis cohort study found that patients with gastric neuroendocrine carcinoma or gastric mixed adenoneuroendocrine carcinoma had worse prognoses and were more prone to distant recurrence than those with gastric adenocarcinoma. Thus, different follow-up and treatment strategies should be developed to improve the long-term survival of patients with gastric neuroendocrine carcinoma or gastric mixed adenoneuroendocrine carcinoma, especially patients with tumors penetrating into the subserosa or deeper layers or with lymph node metastasis.

Dataset Information

Clonality analysis of neuroendocrine cells in gastric adenocarcinoma.

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Clonality analysis of neuroendocrine cells in gastric adenocarcinoma.

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