Evidence map›Paper›PMID 38735658›Full record

ArticleThe Journal of clinical endocrinology and metabolism2024

Coexisting RET/PTC and TERT Promoter Mutation Predict Poor Prognosis but Effective RET and MEK Targeting in Thyroid Cancer.

Wei Zhang, Shuhuang Lin, Zhuo Wang, Wenyong Zhang, Mingzhao Xing

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Article in The Journal of clinical endocrinology and metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
–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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

17 citing papers in PubMed, 1 synthesis or guideline pooled it.

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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.

Wei ZhangThyroid Research Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong 518055, PR China.
Shuhuang LinThyroid Research Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong 518055, PR China.
Zhuo WangThyroid Research Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong 518055, PR China.
Wenyong ZhangThyroid Research Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong 518055, PR China.
Mingzhao XingThyroid Research Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong 518055, PR China.ORCID 0000-0003-4797-610X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

contextThe role of RET/PTC rearrangement in the clinical outcomes of papillary thyroid cancer (PTC) is controversial and remains to be clearly undefined.

objectiveThis work aimed to investigate the role of coexisting RET/PTC rearrangement and TERT promoter mutation in the prognosis and therapeutic targeting in PTC.

methodsA total of 669 PTC patients with complete clinical follow-up and genetic data were pooled from thyroid cancer data sets TCGA-THCA, MSK-MetTropism, and MSK-IMPACT, from whom 163 patients (112 women and 47 men, 4 unknown) with wild-type (WT) BRAF/RAS were identified, with a median age (interquartile range [IQR]) of 46.00 (33.00-61.00) years and a median follow-up time (IQR) of 16.13 (8.09-27.91) months for comparative genotype cohort analysis of mortality.

resultsThere was a significant concurrence index between RET/PTC and TERT promoter mutations, being 2.040 (95% CI, 1.110-3.747; P = .023). Mortality occurred in 5 of 100 (5%) patients harboring neither mutation, 2 of 18 (11.1%) patients harboring a TERT promoter mutation alone, 0 of 31 (0%) patients harboring a RET/PTC alone, and 7 of 14 (50%) patients harboring both genetic alterations, corresponding to hazard ratios (95% CI) of 1 (reference), 2.469 (0.405-14.022), 3.296e-09 (0-inf), and 9.019 (2.635-30.870), respectively, which remained essentially unchanged after adjustment for patient race, sex, and age. Similar results were observed with BRAF/RAS and TERT promoter mutations. Mechanistically, RET/PTC used the MAP kinase pathway to upregulate the mutated TERT, but not the WT TERT, and, correspondingly, targeting RET and MEK could suppress mutated TERT but not the WT TERT.

conclusionCoexisting RET/PTC and TERT promoter mutation identify PTC as a unique clinical entity with high mortality, providing new implications for genetic-based prognostication and potential therapeutic targeting of RET and MEK guided by RET/PTC and TERT status.

Indexed as

MutationPromoter Regions, GeneticProto-Oncogene Proteins c-retTelomeraseThyroid Cancer, PapillaryThyroid NeoplasmsAdultFemaleFollow-Up StudiesGene RearrangementHumansMaleMiddle AgedPrognosisProtein Kinase InhibitorsProtein Kinase InhibitorsProto-Oncogene Proteins c-retRET protein, humanTelomeraseTERT protein, humanmortalityprognostic biomarkerRET/PTCTERT promoter mutationthyroid cancer

Identifiers

PMID38735658
PMCPMC11570377

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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.