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Single-nuclei transcriptomes from human adrenal gland reveal distinct cellular identities of low and high-risk neuroblastoma tumors.

ABSTRACT: Childhood neuroblastoma has a remarkable variability in outcome. Age at diagnosis is one of the most important prognostic factors, with children less than 1 year old having favorable outcomes. Here we study single-cell and single-nuclei transcriptomes of neuroblastoma with different clinical risk groups and stages, including healthy adrenal gland. We compare tumor cell populations with embryonic mouse sympatho-adrenal derivatives, and post-natal human adrenal gland. We provide evidence that low and high-risk neuroblastoma have different cell identities, representing two disease entities. Low-risk neuroblastoma presents a transcriptome that resembles sympatho- and chromaffin cells, whereas malignant cells enriched in high-risk neuroblastoma resembles a subtype of TRKB+ cholinergic progenitor population identified in human post-natal gland. Analyses of these populations reveal different gene expression programs for worst and better survival in correlation with age at diagnosis. Our findings reveal two cellular identities and a composition of human neuroblastoma tumors reflecting clinical heterogeneity and outcome.

SUBMITTER: Bedoya-Reina OC

PROVIDER: S-EPMC8423786 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveThis study aimed to investigate the feasibility of computed tomography (CT) texture analysis for distinguishing canine adrenal gland tumors and its usefulness in clinical decision-making.Materials and methodsThe medical records of 25 dogs with primary adrenal masses who underwent contrast CT and a histopathological examination were retrospectively reviewed, of which 12 had adenomas (AAs), 7 had adenocarcinomas (ACCs), and 6 had pheochromocytomas (PHEOs). Conventional CT evaluation of each adrenal gland tumor included the mean, maximum, and minimum attenuation values in Hounsfield units (HU), heterogeneity of the tumor parenchyma, and contrast enhancement (type, pattern, and degree), respectively, in each phase. In CT texture analysis, precontrast and delayed-phase images of 18 adrenal gland tumors, which could be applied for ComBat harmonization were used, and 93 radiomic features (18 first-order and 75 second-order statistics) were extracted. Then, ComBat harmonization was applied to compensate for the batch effect created by the different CT protocols. The area under the receiver operating characteristic curve (AUC) for each significant feature was used to evaluate the diagnostic performance of CT texture analysis.ResultsAmong the conventional features, PHEO showed significantly higher mean and maximum precontrast HU values than ACC (p < 0.05). Eight second-order features on the precontrast images showed significant differences between the adrenal gland tumors (p < 0.05). However, none of them were significantly different between AA and PHEO, or between precontrast images and delayed-phase images. This result indicates that ACC exhibited more heterogeneous and complex textures and more variable intensities with lower gray-level values than AA and PHEO. The correlation, maximal correlation coefficient, and gray level non-uniformity normalized were significantly different between AA and ACC, and between ACC and PHEO. These features showed high AUCs in discriminating ACC and PHEO, which were comparable or higher than the precontrast mean and maximum HU (AUC = 0.865 and 0.860, respectively).ConclusionCanine primary adrenal gland tumor differentiation can be achieved with CT texture analysis on precontrast images and may have a potential role in clinical decision-making. Further prospective studies with larger populations and cross-validation are warranted.

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Single-nuclei transcriptomes from human adrenal gland reveal distinct cellular identities of low and high-risk neuroblastoma tumors.

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