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PAM staining intensity of primary neuroendocrine neoplasms is a potential prognostic biomarker.

ABSTRACT: Neuroendocrine neoplasms (NENs) are rare epithelial tumors with heterogeneous and frequently unpredictable clinical behavior. Available biomarkers are insufficient to guide individual patient prognosis or therapy selection. Peptidylglycine α-amidating monooxygenase (PAM) is an enzyme expressed by neuroendocrine cells that participates in hormone maturation. The objective of this study was to assess the distribution, clinical associations and survival implications of PAM immunoreactivity in primary NENs. Of 109 primary NENs, 7% were PAM-negative, 25% were PAM-low and 68% were PAM-high. Staining intensity was high in small bowel (p = 0.04) and low in stomach (p = 0.004) NENs. PAM staining was lower in higher grade tumors (p < 0.001) and patients who died (p < 0.001) but did not vary by tumor size or stage at surgery. In patients who died, time to death was shorter in patients with reduced PAM immunoreactivity: median times to death were 11.3 (PAM-negative), 29.4 (PAM-low) and 61.7 (PAM-high) months. Lower PAM staining was associated with increased risk of death after adjusting for disease stage [PAM negative, HR = 13.8 (CI: 4.2-45.5)]. PAM immunoreactivity in primary NENs is readily assessable and a potentially useful stage-independent predictor of survival.

SUBMITTER: Horton TM

PROVIDER: S-EPMC7331689 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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PAM staining intensity of primary neuroendocrine neoplasms is a potential prognostic biomarker.

Horton Timothy M TM Sundaram Vandana V Lee Christine Hye-Jin CH Hornbacker Kathleen K Van Vleck Aidan A Benjamin Kaisha N KN Zemek Allison A Longacre Teri A TA Kunz Pamela L PL Annes Justin P JP

Scientific reports 20200702 1

Neuroendocrine neoplasms (NENs) are rare epithelial tumors with heterogeneous and frequently unpredictable clinical behavior. Available biomarkers are insufficient to guide individual patient prognosis or therapy selection. Peptidylglycine α-amidating monooxygenase (PAM) is an enzyme expressed by neuroendocrine cells that participates in hormone maturation. The objective of this study was to assess the distribution, clinical associations and survival implications of PAM immunoreactivity in prima ...[more]

PMID: 32616904

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Project description:Background: Small intestinal neuroendocrine tumors (SI-NETs) are the most common malignant tumors of the small intestine, with many patients presenting with metastases and their incidence increasing. We aimed to find effective diagnostic biomarkers for patients with primary and metastatic SI-NETs that could be applied for clinical diagnosis. Methods: We downloaded GSE65286 (training set) and GSE98894 (test set) from the GEO database and performed differential gene expression analysis to obtain differentially expressed genes (DEGs) and differentially expressed long non-coding RNAs (DElncRNAs). The functions and pathways involved in these genes were further explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. In addition, a global regulatory network involving dysregulated genes in SI-NETs was constructed based on RNAInter and TRRUST v2 databases, and the diagnostic power of hub genes was identified by receiver operating characteristic curve (ROC). Results: A total of 2,969 DEGs and DElncRNAs were obtained in the training set. Enrichment analysis revealed that biological processes (BPs) and KEGG pathways were mainly associated with cancer. Based on gene set enrichment analysis (GSEA), we obtained five BPs (cytokinesis, iron ion homeostasis, mucopolysaccharide metabolic process, platelet degranulation and triglyceride metabolic process) and one KEGG pathway (ppar signaling pathway). In addition, the core set of dysregulated genes obtained included MYL9, ITGV8, FGF2, FZD7, and FLNC. The hub genes were upregulated in patients with primary SI-NETs compared to patients with metastatic SI-NETs, which is consistent with the training set. Significantly, the results of ROC analysis showed that the diagnostic power of the hub genes was strong in both the training and test sets. Conclusion: In summary, we constructed a global regulatory network in SI-NETs. In addition, we obtained the hub genes including MYL9, ITGV8, FGF2, FZD7, and FLNC, which may be useful for the diagnosis of patients with primary and metastatic SI-NETs.

Project description:BackgroundThe prognostic factors and optimal choice of treatment for primary neuroendocrine neoplasms of the breast (BNEN) remain to be defined.MethodsPatients diagnosed with BNEN in China were retrospectively reviewed from the literature following the systematic search of China National Knowledge Infrastructure (CNKI), Chinese biomedical literature service system (sinomed), wanfang medical network, and Pubmed database. The clinical characteristics and different treatment modalities of patients with BNEN were evaluated.ResultsA total of 209 cases with BNEN were enrolled. There were 204 female and 5 male patients. The median age was 51 years old (range, 17-82). Out of 209 patients with BNEN, 208 (99.5%) patients were treated with surgery (SG), 44 patients (21.1%) had received radiotherapy (RT), 173 patients (82.8%) experienced chemotherapy (CT). A total of 158 patients with hormone receptor (HR) positive (87.8%, 158/180) were treated with endocrine treatment (ET). The median follow-up time was 52.4 months (range, 6-144). The 3-year overall survival (OS) rate and 3-year disease-free survival (DFS) rate for the whole group were 93.7% and 85.3%, respectively. In univariate analyses, Ki67 expression ≥20%, HR negative, neuroendocrine carcinomas (NECs) were associated with decreased OS and DFS (P < 0.05). Patients treated with anthracycline/taxane-containing CT regimens, or taxane-containing CT regimens had superior OS and DFS than patients without those (P < 0.05). Among 69 patients with stage I who received CT had no significant differences in OS or DFS compared to those without CT. Multivariate Cox regression analysis showed that gender, HR expression, pathologic subtype, and CT were independent prognostic factors for DFS but not OS (P > 0.05).ConclusionsThe best selection of patients to get the most benefit from different treatment modalities warrant further exploration. The clinicopathological parameters including gender, HR expression, ki67 expression, pathologic type, stage, tumor size, and lymph node status may serve as both indicators of diagnosis and prognosis, and guide treatment decisions for BNEN.

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PAM staining intensity of primary neuroendocrine neoplasms is a potential prognostic biomarker.

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PAM staining intensity of primary neuroendocrine neoplasms is a potential prognostic biomarker.

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