Evidence map›Paper›PMID 42518368›Full record

ArticleHuman mutation2026

Integrative Mendelian Randomization and Single-Cell Pseudotime Analysis Reveal DKK3 as a PI3K-AKT-Modulated Driver of Esophageal Squamous Cell Carcinoma.

Zhanghao Huang, Tiegang Cao, You Lang Zhou, Jiahai Shi

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PubMed Full text at PMC Publisher
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Article in Human mutation, 2026. 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

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

1 citing paper in PubMed.

  1. Article
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

4 authors.

Zhanghao HuangMedical School of Nantong University, Nantong University, Nantong, Jiangsu, China, ntu.edu.cn.ORCID https://orcid.org/0000-0002-3223-8625
Tiegang CaoMedical School of Nantong University, Nantong University, Nantong, Jiangsu, China, ntu.edu.cn.ORCID https://orcid.org/0009-0003-4616-2718
You Lang ZhouResearch Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China, ahnmc.com.ORCID https://orcid.org/0009-0001-1688-8548
Jiahai ShiDepartment of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China, ahnmc.com.ORCID https://orcid.org/0000-0002-8635-5376

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) remains a highly lethal malignancy, and the molecular drivers of its progression are not fully defined. Dickkopf-3 (DKK3), a context-dependent modulator of oncogenic signaling, has been implicated in several solid tumors, but its role in ESCC is unclear. Methods: We integrated Mendelian randomization based on cis-expression quantitative trait loci (cis-eQTLs) from 31,684 individuals with The Cancer Genome Atlas (TCGA) ESCC transcriptomic data (|log Results: Integrative differential expression and MR analyses identified 22 ESCC-associated genes. Single-cell epithelial profiling further prioritized three candidates (DKK3, NINJ2, and SAPCD2), among which only DKK3 showed high and progressively increasing expression along the malignant epithelial trajectory and was therefore selected for mechanistic validation. DKK3 knockdown significantly inhibited ESCC cell proliferation, migration, and clonogenic capacity in vitro and suppressed tumor growth in nude mice. DKK3 silencing reduced p-PI3K and p-AKT levels, and enrichment analyses supported that DKK3 promotes ESCC progression at least partly through activation of the PI3K-AKT signaling pathway. Conclusion: By linking germline regulatory variation with single-cell tumor profiling and functional validation, this study identifies DKK3 as a causally relevant oncogenic regulator in ESCC that drives epithelial tumor growth and migration via PI3K-AKT pathway activation, supporting DKK3 as a potential biomarker and therapeutic targe.

Indexed as

Adaptor Proteins, Signal TransducingEsophageal NeoplasmsEsophageal Squamous Cell CarcinomaIntercellular Signaling Peptides and ProteinsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktAnimalsCell Line, TumorCell MovementCell ProliferationChemokinesGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMiceSignal TransductionAdaptor Proteins, Signal TransducingChemokinesDKK3 protein, humanIntercellular Signaling Peptides and ProteinsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktDKK3esophageal squamous cell carcinomaMendelian randomizationPI3K–AKT signaling pathwaysingle-cell analysis

Identifiers

PMID42518368
PMCPMC13383006

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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.