Evidence map›Paper›PMID 37268816›Full record

ArticleCancer gene therapy2023

Multi-cancer analysis reveals universal association of oncogenic LBH expression with DNA hypomethylation and WNT-Integrin signaling pathways.

In-Chi Young, Thomas Brabletz, Linsey E Lindley, Maria Abreu, Nagaraj Nagathihalli, Alexander Zaika, Karoline J Briegel

Open access · hybridAbstract read
In one paragraph

Article in Cancer gene therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.2field-weighted citation impact, top 13% of its field
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

18 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. Integrative systems biology analysis reveals diagnostic and prognostic DNA methylation signatures in esophageal cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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  8. CpG Methylation Protects DNA against Ionizing Radiation.The journal of physical chemistry. B · 2025
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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

7 authors at 2 institutions in 2 countries.

In-Chi YoungDepartment of Surgery, Division of Surgical Oncology, University of Miami Miller School of Medicine, Miami, FL, USA.
Thomas BrabletzDepartment of Experimental Medicine 1, Nikolaus-Fiebiger-Center for Molecular Medicine, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.ORCID http://orcid.org/0000-0003-2983-9048
Linsey E LindleyBraman Family Breast Cancer Institute, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
Maria AbreuDepartment of Medicine, Division of Gastroenterology, University of Miami Miller School of Medicine, Miami, FL, USA.
Nagaraj NagathihalliDepartment of Surgery, Division of Surgical Oncology, University of Miami Miller School of Medicine, Miami, FL, USA.
Alexander ZaikaDepartment of Surgery, Division of Surgical Oncology, University of Miami Miller School of Medicine, Miami, FL, USA.
Karoline J BriegelDepartment of Surgery, Division of Surgical Oncology, University of Miami Miller School of Medicine, Miami, FL, USA. kbriegel@med.miami.edu.ORCID http://orcid.org/0000-0003-2661-509X
University of Miami · USFriedrich-Alexander-Universität Erlangen-Nürnberg · DE

Funding

SOX4-Mediated Transcription Program in Esophageal AdenocarcinomaP01CA268991 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI WAEL EL-RIFAI · 2022 to 2026
$9.2M
Regulation of the Oncogenic Stress Response in Helicobacter pylori-infected cellsR01CA138833 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ALEXANDER I. ZAIKA · 2010 to 2026
$4.3M
Cell-Intrinsic Regulation of the Mammary Stem Cell NicheR01GM113256 · NIGMS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI BRIEGEL, KAROLINE JOSEFINE · 2015 to 2019
$1.5M
Regulation of gastroesophageal reflux-associated tumorigenesisI01BX002115 · VA · VETERANS HEALTH ADMINISTRATION · PI ZAIKA, ALEXANDER I. · 2014 to 2024
–
BLRD Research Career Scientist Award ApplicationIK6BX006300 · VA · MIAMI VA HEALTH CARE SYSTEM · PI ZAIKA, ALEXANDER I. · 2023 to 2025
–
BLRD VA I01 BX002115BLRD VA IK6 BX006300NCI NIH HHS P01 CA268991NCI NIH HHS R01 CA138833NIGMS NIH HHS R01 GM113256
6 · The paper itself

Abstract

Limb-Bud and Heart (LBH) is a developmental transcription co-factor deregulated in cancer, with reported oncogenic and tumor suppressive effects. However, LBH expression in most cancer types remains unknown, impeding understanding of its mechanistic function Here, we performed systematic bioinformatic and TMA analysis for LBH in >20 different cancer types. LBH was overexpressed in most cancers compared to normal tissues (>1.5-fold; p < 0.05), including colon-rectal, pancreatic, esophageal, liver, stomach, bladder, kidney, prostate, testicular, brain, head & neck cancers, and sarcoma, correlating with poor prognosis. The cancer types showing LBH downregulation were lung, melanoma, ovarian, cervical, and uterine cancer, while both LBH over- and under-expression were observed in hematopoietic malignancies. In cancers with LBH overexpression, the LBH locus was frequently hypomethylated, identifying DNA hypomethylation as a potential mechanism for LBH dysregulation. Pathway analysis identified a universal, prognostically significant correlation between LBH overexpression and the WNT-Integrin signaling pathways. Validation of the clinical association of LBH with WNT activation in gastrointestinal cancer cell lines, and in colorectal patient samples by IHC uncovered that LBH is specifically expressed in tumor cells with nuclear beta-catenin at the invasive front. Collectively, these data reveal a high degree of LBH dysregulation in cancer and establish LBH as pan-cancer biomarker for detecting WNT hyperactivation in clinical specimens.

Indexed as

NeoplasmsTranscription Factorsbeta CateninCell LineCell Line, TumorDNADNA MethylationGene Expression Regulation, NeoplasticHumansMaleWnt Signaling Pathwaybeta CateninDNALBH protein, humanTranscription Factors

Identifiers

PMID37268816
PMCPMC10501907
OpenAlexW4379197360

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.