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Diagnosis and Molecular Profiles of Large Cell Neuroendocrine Carcinoma With Potential Targets for Therapy.

ABSTRACT: Large cell neuroendocrine carcinoma (LCNEC) together with small cell carcinoma (SCLC) and typical and atypical carcinoids form the group of pulmonary neuroendocrine tumors. LCNEC and SCLC are high-grade carcinomas. Although both can be found outside the thoracic cavity, they are most common in the lung. LCNEC differs from SCLC by morphologic pattern, and by cytological features such as nuclear size, nucleoli, chromatin pattern, but also by genetic differences. Originally thought to represent a single entity, it became evident, that three subgroups of LCNEC can be identified at the molecular level: a SCLC-like type with loss of retinoblastoma 1 gene (RB1) and TP53 mutations; a non-small cell lung carcinoma (NSCLC)-like type with wildtype RB1, TP53 mutation, and activating mutations of the phosphoinositol-3 kinase (PI3K-CA), or loss of PTEN; and a carcinoid-like type with MEN1 gene mutation. These subtypes can be identified by immunohistochemical staining for RB1, p53, and molecular analysis for PI3K and MEN1 mutations. These subtypes might also respond differently to chemotherapy. Immuno-oncologic treatment has also been applied to LCNEC, however, in addition to the evaluation of tumor cells the stroma evaluation seems to be important. Based on personal experiences with these tumors and available references this review will try to encompass our present knowledge in this rare entity and provoke new studies for better treatment of this carcinoma.

SUBMITTER: Popper H

PROVIDER: S-EPMC8293294 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe incidence of esophageal squamous cell carcinoma in China ranks first in the world. The early diagnosis technology is underdeveloped, and the prognosis is poor, which seriously threatens the quality of life of the Chinese people. Epidemiological findings are related to factors such as diet, living habits, and age. The specific mechanism is not clear yet. Metabolomics is a kind of omics that simultaneously and quantitatively analyzes the comprehensive profile of metabolites in living systems. It has unique advantages in the study of the diagnosis and pathogenesis of tumor-related diseases, especially in the search for biomarkers. Therefore, it is desirable to perform metabolic profiling analysis of cancer tissues through metabolomics to find potential biomarkers for the diagnosis and treatment of esophageal squamous cell carcinoma.MethodsHPLC-TOF-MS/MS technology and Illumina Hiseq Xten Sequencing was used for the analysis of 210 pairs of matched esophageal squamous cell carcinoma tissues and normal tissues in Zhenjiang City, Jiangsu Province, a high-incidence area of esophageal cancer in China. Bioinformatics analysis was also performed.ResultsThrough metabolomic and transcriptomic analysis, this study found that a total of 269 differential metabolites were obtained in esophageal squamous cell carcinoma and normal tissues, and 48 differential metabolic pathways were obtained through KEGG enrichment analysis. After further screening and identification, 12 metabolites with potential biomarkers to differentiate esophageal squamous cell carcinoma from normal tissues were obtained.ConclusionsFrom the metabolomic data, 4 unknown compounds were found to be abnormally expressed in esophageal squamous cell carcinoma for the first time, such as 9,10-epoxy-12,15-octadecadienoate; 3 metabolites were found in multiple abnormal expression in another tumor, but upregulation or downregulation was found for the first time in esophageal cancer, such as oleoyl glycine; at the same time, it was further confirmed that five metabolites were abnormally expressed in esophageal squamous cell carcinoma, which was similar to the results of other studies, such as PE.

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Diagnosis and Molecular Profiles of Large Cell Neuroendocrine Carcinoma With Potential Targets for Therapy.

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