Project description:Tumor tissue of lung carcinoid tumors (pulmonary neuroendocrine tumors) and adjacent normal lung tissue was profiled using scRNA-seq
Project description:Pulmonary carcinoid tumors account for up to 5% of all lung malignancies in adults, comprise 30% of all carcinoid malignancies, and are defined histologically as typical carcinoid (TC) and atypical carcinoid (AC) tumors. The role of specific genomic alterations in the pathogenesis of pulmonary carcinoid tumors remains poorly understood. We sought to identify genomic alterations and pathways that are deregulated in these tumors to find novel therapeutic targets for pulmonary carcinoid tumors.We performed integrated genomic analysis of carcinoid tumors comprising whole genome and exome sequencing, mRNA expression profiling and SNP genotyping of specimens from normal lung, typical and atypical carcinoid, and small cell lung carcinoma (SCLC) to fully represent the lung neuroendocrine tumor spectrum. Pathway analysis of of CNV and gene expression data suggested deregulation of the NF-ĸB and MAPK/ERK pathways. This study identified mutated genes affecting cancer relevant pathways and biological processes that could provide opportunities for developing targeted therapies for pulmonary carcinoid tumors.
Project description:We identify genes presenting a specific expression profile in midgut carcinoid cells, primary carcinoids tumors and liver metastasis were gene profiled. Gene expression profiling of classical midgut carcinoid primary tumors and liver metastasis reveal potential novel therapeutic targets and molecular signatures. Experiment Overall Design: Normal and tumoral (carcinoid) cells
Project description:We aimed to identify clinically meaningful biomarkers in pulmonary carcinoid tumors (PCTs), a member of neuroendocrine neoplasms, via profiling miRNAs and mRNAs.
Project description:We report RNA sequencing data for miR-375 knockout and YAP overexpression lung carcinoid cells (H727). Lung carcinoids are variably aggressive and mechanistically understudied neuroendocrine neoplasms (NENs). Here, we identified and elucidated the function of a miR-375/yes-associated protein (YAP) axis in lung carcinoid (H727) cells. miR-375 and YAP are respectively high and low expressed in wild-type H727 cells. Following lentiviral CRISPR/Cas9-mediated miR-375 depletion, we identified distinct transcriptomic changes including dramatic YAP upregulation. Similarly, YAP overexpression resulted in distinct and partially overlapping transcriptomic changes, phenocopying the effects of miR-375 depletion in the same models as above. Pathways analysis and confirmatory real-time PCR studies of shared dysregulated targets indicate that this axis controls neuroendocrine related functions such as neural differentiation, exocytosis, and secretion. Taken together, we provide compelling evidence that a miR-375/YAP axis is a critical mediator of neuroendocrine differentiation and tumorigenesis in lung carcinoid cells.
Project description:In order to clarify the gene expression and identify genes involved in tumor progression, gene expression profiling was performed on tumor specimens. Samples comprised 18 primary tumors, 17 lymph node (LN) metastases and 7 liver metastases. Patients were grouped according to clinical data and histopathology into indolent or progressive course. RNA was subjected to a spotted oligo microarray and B-statistics were performed. Differentially expressed genes were verified using quantitative RT-PCR. Self-organising maps demonstrated three clusters. Eleven primary tumors separated in one cluster, 5 LN metastases in another whereas all liver metastases, 7 primary and 12 LN metastases, formed a third cluster. There was no correlation between indolent and progressive behaviour. The primary tumors with Ki67 > 5%, with low frequency of the carcinoid syndrome and a tendency towards shorter survival grouped together. Primary tumors differed in expression profile from their associated LN metastases. ACTG2, GREM2, REG3A, TUSC2, RUNX1, TPH1, TGFBR2 and CDH6 were differentially expressed between clusters and subgroups of tumors. The expression profile that assembles tumors as being genetically similar on the RNA expression level may not be concordant with the clinical disease course. This study reveals different gene expression profiles and novel genes not previously known to be involved in neuroendocrine tumorigenesis, and which may be of importance for tumor progression.