Evidence map›Paper›PMID 40528170›Full record

ArticleJournal of translational medicine2025

Integrating multi-omics to unveil PSMD12 as a critical gene in promoting brain metastases of lung adenocarcinoma.

Xin Li, Juxuan Zhang, Meng Zhang, Wenbin Jiang, Dexin Jia, Ruxiong Wang, Hao Li, Zhihui Wang, Yixin Liu, Lefan Tang and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

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

3 citing papers in PubMed.

  1. Article
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  3. 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

15 authors.

Xin Li *College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China.
Juxuan Zhang *College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China.
Meng Zhang *College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China.
Wenbin JiangCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China.
Dexin JiaDepartment of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150040, China.
Ruxiong WangDepartment of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150040, China.
Hao LiCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China.
Zhihui WangCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China.
Yixin LiuCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China.
Lefan TangCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China.
Jiaxing DengCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China.
Wenyuan ZhaoCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China.
Yan YuDepartment of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150040, China. yuyan@hrbmu.edu.cn.ORCID 0000-0001-5598-763X
Shilong LiuDepartment of Thoracic Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, China. liushilong19840614@163.com.
Lishuang QiCollege of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150086, China. qilishuang7@ems.hrbmu.edu.cn.ORCID 0000-0002-2991-6544

Funding

Heilongjiang Postdoctoral Fund LBH-Z21081National Natural Science Foundation of China 32370716National Natural Science Foundation of China 62473119National Natural Science Foundation of China 82373041Outstanding Youth Foundation of Heilongjiang Province of China YQ2023H002Postgraduate Research & Practice Innovation Program of Harbin Medical University YJSCX2024-24HYD
6 · The paper itself

Abstract

backgroundBrain metastases (BM) remain the leading cause of death in patients with lung adenocarcinoma (LUAD) despite the availability of comprehensive therapeutics. This study aimed to systematically identify crucial genes associated with BM in patients with LUAD, and develop a heuristic search algorithm combining information filtering and multiple stepwise regression to construct a multi-layered transcription factor regulatory network.

methodsWe used the mRNA expression profiles of primary tumours derived from LUAD patients with different organ metastasis and adjacent normal tissue samples to identify differentially expressed genes specific to BM, and validated it in bulk, spatial and single-cell RNA-sequencing data. Furthermore, we collected 110 stage I-III LUAD specimens to validate the correlation of high PSMD12 (proteasome 26 S subunit, non-ATPase 12) protein expression with BM incidence and patient prognosis. We also developed an in vitro blood-brain barrier (BBB) model to investigate the disruption of PSMD12 on the barrier. Mechanistically, we developed an algorithm to construct an upstream regulator network of PSMD12 overexpression.

resultsThrough integrated bioinformatics analyses, we identified PSMD12 as a critical gene associated with BM. The associations of PSMD12 with BM and poor survival were validated in multiple public datasets comprising 706 patients. Immunohistochemical results confirmed that patients exhibiting high PSMD12 protein expression had a significantly higher incidence of BM within 5 years and shorter progression-free survival. Functional experiments revealed that PSMD12 overexpression in A549 cells disrupted BBB integrity and enhanced tumor cell invasiveness, whereas PSMD12 knockdown attenuated these effects. Furthermore, upstream regulator network and knockdown experiments indicated that downregulated EOMES expression would contribute to PSMD12 overexpression.

conclusionsPSMD12 emerges as a crucial gene in promoting BM, potentially serving as an early warning indicator of BM in early-stage LUAD. The upstream regulatory network of PSMD12 overexpression provides potential mechanisms for BM in LUAD patients.

Indexed as

Adenocarcinoma of LungBrain NeoplasmsLung NeoplasmsProteasome Endopeptidase ComplexBlood-Brain BarrierCell Line, TumorFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGene Regulatory NetworksHumansMaleMultiomicsPrognosisReproducibility of ResultsProteasome Endopeptidase ComplexBrain metastasisIn vitro blood–brain barrierLung adenocarcinomaPSMD12TF regulatory network

Identifiers

PMID40528170
PMCPMC12175416

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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 Socratic graph.