Evidence map›Paper›PMID 41498635›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

Single-Nucleus Multi-Omics Reveals Hypoxia-Driven Angiogenic Programs and Their Epigenetic Control in Sinonasal Squamous Cell Carcinoma.

Chaelin You, Jaewoo Park, Jung Yeon Jang, Junho Noh, Jaehyun Lee, Geunho Kwon, Myeong Sang Yu, Yoo-Sam Chung, Seung-Jun Lee, Keunsoo Kang and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

13 authors.

Chaelin YouDepartment of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Republic of Korea.ORCID https://orcid.org/0009-0007-4483-7952
Jaewoo ParkDepartment of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Republic of Korea.
Jung Yeon JangDepartment of Otorhinolaryngology-Head and Neck Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Junho NohDepartment of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Republic of Korea.
Jaehyun LeeDepartment of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Republic of Korea.
Geunho KwonDepartment of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Republic of Korea.
Myeong Sang YuDepartment of Otorhinolaryngology-Head and Neck Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Yoo-Sam ChungDepartment of Otorhinolaryngology-Head and Neck Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Seung-Jun LeeResearch Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
Keunsoo KangDepartment of Microbiology, College of Science & Technology, Dankook University, Cheonan, Republic of Korea.
Jihwan ParkSchool of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju, Republic of Korea.
Ji Heui KimDepartment of Otorhinolaryngology-Head and Neck Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Kyuho KangDepartment of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Republic of Korea.ORCID https://orcid.org/0000-0003-3448-5336

Funding

Asan Institute for Life Sciences, Asan Medical Center 2023IP0057National Research Foundation NRF-2022R1A2C1011187National Research Foundation RS-2024-00340411National Research Foundation RS-2024-00412747
6 · The paper itself

Abstract

Sinonasal squamous cell carcinoma (SNSCC) is a rare malignancy with poorly understood molecular drivers. Consequently, its cellular composition and tumor microenvironment (TME) remain largely undefined. Here, we performed integrated bulk and single-nucleus multi-omic analyses to map the SNSCC ecosystem. Within the malignant compartment, we identified five distinct populations, with hypoxic (TC1) and proliferative (TC2) subtypes associated with adverse clinical outcomes. Functionally, TC1 cells orchestrate a hypoxia-driven angiogenic program via coordinated secretion of adrenomedullin (ADM), MIF, and VEGFA, promoting endothelial tip cell (EC1) differentiation. Integrative analysis revealed these transcriptional programs are underpinned by tumor-specific chromatin accessibility and DNA hypomethylation, particularly at AP-1-enriched regulatory elements. Mechanistically, in vitro studies confirmed that this response depends on cooperative AP-1 and HIF1A signaling. Furthermore, histological analysis of patient tissues demonstrated spatial co-localization of GLUT1-expressing TC1 cells with DLL4-positive EC1 cells. These findings elucidate the epigenetic landscape underlying tumor-stromal interactions and establish the ADM/VEGFA axis as a critical therapeutic target to disrupt epigenetically controlled angiogenesis in SNSCC.

Indexed as

Carcinoma, Squamous CellEpigenesis, GeneticHypoxiaNeovascularization, PathologicParanasal Sinus NeoplasmsCell Line, TumorGene Expression Regulation, NeoplasticHumansMultiomicsTumor Microenvironmenthypoxia‐angiogenesis axismulti‐omic profilingrare cancer genomicssinonasal squamous cell carcinomatumor heterogeneity

Identifiers

PMID41498635
PMCPMC12948189

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 OpenQuestion graph.