Evidence map›Paper›PMID 38819743›Full record

ArticleHormones (Athens, Greece)2024

Somatic USP8 alteration affects the immune landscape of corticotroph pituitary adenomas- a pilot study.

Dahlia Greidinger, Reut Halperin, Roni Zemet, Nitzan Maixner, Amit Tirosh

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Article in Hormones (Athens, Greece), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Dahlia Greidinger *Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.
Reut Halperin *Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.
Roni ZemetFaculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.
Nitzan MaixnerCancer Center at Chaim Sheba Medical Center, Tel HaShomer, Israel.
Amit TiroshFaculty of Medicine, Tel Aviv University, Tel-Aviv, Israel. amit.tirosh@sheba.health.gov.il.ORCID http://orcid.org/0000-0003-3794-9634

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionSomatic mutations in ubiquitin-specific protease-8 (USP8), encoding a deubiquinating protein, are found in approximately 30% of corticotroph-derived pituitary adenomas (CPAs). Stratifin, a protein encoded by SFN, inhibits USP8 catalytic activity. USP8 has immunomodulating properties that have been demonstrated in non-tumoral diseases.

methodsWe assessed the influence of USP8 on the immune landscape of CPA and validated this effect and its dependency on stratifin in large cohorts of non-pituitary tumors. We analyzed data of CPA samples (n = 20) and additional non-pituitary tumors from the TCGA database, using transcriptome signature-recognition algorithms. Immune tumor microenvironment (iTME) was compared both by USP8 and SFN expression levels (n = 843) and by USP8 mutation status and SFN expression (n = 12,389).

resultsCPA with activating USP8 mutations was associated with "cold" iTME compared with wild-type USP8 CPA, as reflected by lower fractions of immune cells, including B cells, CD4, regulatory and gamma/delta T cells, natural killer cells, M0 and M1 macrophages, dendritic cells, and eosinophils (p < 0.05 for all comparisons). Pathways altered by the presence of USP8 mutation, based on the most differentially expressed genes (3061 genes), included microglia pathogen phagocytosis and multiple toll-like receptor signaling pathways (p < 0.0001). In a validation analysis based on large cohorts of non-pituitary tumors, high expression of USP8 was associated with a suppressed iTME effect that was augmented by a low SFN expression.

conclusionsOur data demonstrate for the first time, to our knowledge, a distinct immune landscape of tumors based on USP8 status and expression and the dependency of this immunological effect on SFN expression.

Indexed as

Endosomal Sorting Complexes Required for TransportMutationTumor MicroenvironmentUbiquitin ThiolesteraseACTH-Secreting Pituitary AdenomaAdenomaEndopeptidasesFemaleHumansMalePilot ProjectsEndopeptidasesEndosomal Sorting Complexes Required for TransportUbiquitin ThiolesteraseUSP8 protein, humanCorticotrophImmune microenvironmentPituitary adenomaUSP8

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.