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Record W4410852312 · doi:10.1371/journal.pone.0313380

Alpha thalassemia/mental retardation X-linked (ATRX) protein expression in human pituitary neuroendocrine tumours and its reported correlation to prognosis and clinical outcomes: A systematic review

2025· review· en· W4410852312 on OpenAlexaff
Fabio Rotondo, Michael D. Cusimano

Bibliographic record

VenuePLoS ONE · 2025
Typereview
Languageen
FieldMedicine
TopicGlioma Diagnosis and Treatment
Canadian institutionsPublic Health OntarioUniversity of TorontoSt. Michael's Hospital
Fundersnot available
KeywordsATRXCarcinogenesisCancer researchSynthetic lethalityBiologyEpigeneticsTelomereNeuroendocrine tumorsMedicineCancerBioinformaticsOncologyInternal medicineGeneticsMutationDNA repairGene

Abstract

fetched live from OpenAlex

Mutations in Alpha thalassemia/mental retardation X-linked (ATRX) have been implicated in several cancers, including gliomas, sarcomas, neuroendocrine tumors, and other mesenchymal malignancies. ATRX loss contributes to oncogenesis, accelerates tumor growth, and reduces survival by disrupting epigenetic and telomere mechanisms. Additionally, ATRX loss can increase tumor sensitivity to treatment therapies. While research has explored ATRX expression in many cancers, data on its relationship to prognosis in pituitary neuroendocrine tumors (PitNETs) remain inconsistent. This systematic review aims to summarize all available studies on ATRX mutations and expression in PitNETs. A systematic search of PubMed, Scopus, and EMBASE databases was conducted to identify publications between 2014 and 2025 that investigated ATRX mutations or expression in PitNETs, following PRISMA 2020 guidelines. Of 32 identified studies, ten met the inclusion criteria, covering a total of 513 PitNETs. Only 20 tumors (3.9%) showed a loss of ATRX expression. Among these, 60% exhibited corticotrophic pathology, while 20% displayed lactotrophic pathology. A small subset of tumors (30%) was classified as pituitary carcinomas with aggressive and proliferative characteristics. Additionally, 10% demonstrated the alternative lengthening of telomeres (ALT) phenotype, 50% had concurrent TP53 mutations, and 25% had elevated Ki-67 indices, indicating a higher proliferative index. Although ATRX mutations are rare in PitNETs, tumors with ATRX loss tend to be more aggressive and exhibit proliferative and transformative properties. Due to the limited number of cases, further studies with larger, prospective cohorts are needed to better understand the role of ATRX loss in PitNET progression and aggressiveness.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.004
metaresearch head score (Gemma)0.014
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Systematic review · Consensus signal: Systematic review
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.014
Threshold uncertainty score0.019

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0040.014
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0070.006
Bibliometrics0.0140.017
Science and technology studies0.0010.001
Scholarly communication0.0020.002
Open science0.0020.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0040.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.108
GPT teacher head0.380
Teacher spread0.272 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designSystematic review
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations2
Published2025
Admission routes1
Has abstractyes

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