Evidence map›Paper›PMID 42807949›Full record

ArticleInternational journal of biological sciences2026

Genomic and Transcriptomic Landscapes of MEN1-Wild-Type Low-Grade Metastatic Pancreatic NETs Uncover Key Oncogenic Drivers and Targetable Pathways.

Md Hafiz Uddin, Zaid Mahdi, Irfana Muqbil, Brendon R Herring, Bart Rose, Husain Y Khan, Yiwei Li, Amro Aboukameel, Sahar F Bannoura, Hugo Jimenez and 21 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of biological sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

31 authors.

Md Hafiz UddinKarmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Zaid MahdiEmory Winship Cancer Institute, Atlanta, GA, USA.
Irfana MuqbilLawrence Technological University, Southfield, MI, USA.
Brendon R HerringO'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA.
Bart RoseO'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA.
Husain Y KhanKarmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Yiwei LiKarmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Amro AboukameelKarmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Sahar F BannouraKarmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Hugo JimenezKarmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Allan M JohansenDepartment of Cancer Biology, Wake Forest University, Winston-Salem, NC, USA.
Mohammed Najeeb Al-HallakKarmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Ibrahim AzarKarmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Amr MohamedUH Seidman Cancer Center, University Hospitals, Case Western Reserve University, Cleveland, OH, USA.
Tarik HadidKarmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Nitin VaishampayanKarmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Yang ShiKarmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Yin WanKarmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Vy OngKarmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Gregory DysonKarmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Rafic BeydounDepartment of Pathology, Wayne State University School of Medicine, Wayne State University, Detroit, MI, USA.
Miguel TobonKarmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Eliza W BealKarmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Herbert ChenO'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA.
Anthony F ShieldsKarmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Philip A PhilipKarmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Jennifer Beebe-DimmerKarmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Ramzi M MohammadKarmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Boris C PascheKarmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Bassel F El-RayesDivision of Medical Oncology, Moores Cancer Center, UC San Diego, La Jolla, CA, 92037, USA.
Asfar S AzmiKarmanos Cancer Institute, Wayne State University, Detroit, MI, USA.

Funding

Tumor Biology and Microenvironment (Program 1)P30CA022453 · NCI · WAYNE STATE UNIVERSITY · PI PAUL M STEMMER · 1985 to 2026
$68.4M
A novel therapy for pancreatic neuroendocrine tumorsR01CA240607 · NCI · WAYNE STATE UNIVERSITY · PI AZMI, ASFAR S, EL-RAYES, BASSEL · 2020 to 2024
$1.7M
NCI NIH HHS P30 CA022453NCI NIH HHS R01 CA240607
6 · The paper itself

Abstract

Sporadic pancreatic neuroendocrine tumors (pNETs) with wild-type MEN1 represent a major yet largely ignored subset whose biology and metastatic potential remain poorly understood. Because metastasis can occur despite low histologic grade and modest mutational burden, we hypothesized that metastatic competence in MEN1-wild-type pNETs reflects quantitative reinforcement of shared oncogenic pathways rather than distinct mutational processes. We profiled 75 primary WHO G1/G2 pNETs by whole-exome and RNA sequencing, including 25% with lymph node and/or liver metastasis, and integrated genomic and transcriptomic data to connect pathway lesions with expression state. Metastatic tumors showed a slight increase in mutation frequency but conserved base-substitution spectra relative to non-metastatic cases, and adverse clinicopathologic features were enriched in Grade 2 disease. Aggregating alterations to pathways revealed broad convergence on canonical networks, with transcriptomic analyses demonstrating cohort-wide enrichment of Calcium, WNT, and KRAS/PI3K-AKT programs in metastasis. Intersection of significantly mutated genes with differentially expressed genes identified a focused 29-gene overlap, including RYR1 and ZNF273, that marks these convergent axes and distinguishes metastatic from non-metastatic tumors. Gene set enrichment confirmed preferential activation of Calcium, WNT, and PI3K-AKT signaling in metastatic tumors, consistent with a network-intensity model of progression. Finally, upstream-regulator analysis (iPathwayGuide) and gene-centric perturbation mapping (Gene2Drug) nominated candidate targeted and repurposable agents predicted to reverse the metastatic expression phenotype and flagged drugs unlikely to provide benefit, yielding a prioritized, testable therapeutic shortlist which includes fasudil and spaglumic acid. Convergent, domain-specific mutational patterns in highly mutated genes such as ZNF273 and CLCA1 define a molecular signature that could stratify metastatic risk in low-grade pNETs. Functional validation identified ZNF273 and RYR1 as candidate effectors of metastatic fitness in MEN1-wild-type pNETs, as siRNA-mediated silencing reduced cell viability, clonogenicity, spheroid growth, and migration in BON1 and QGP1 models. Predicted compounds showed

Indexed as

Neuroendocrine TumorsPancreatic NeoplasmsTranscriptomeGene Expression Regulation, NeoplasticGenomicsHumansMutationSignal Transductiongenomic and transcriptomic characterizationlow grademetastasismutationpancreatic neuroendocrine tumorstherapeutic candidates

Identifiers

PMID42807949
PMCPMC13618231

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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.