Evidence map›Paper›PMID 37686653›Full record

ArticleCancers2023

A Network Landscape of HPVOPC Reveals Methylation Alterations as Significant Drivers of Gene Expression via an Immune-Mediated GPCR Signal.

Jesse R Qualliotine, Takuya Nakagawa, Sara Brin Rosenthal, Sayed Sadat, Carmen Ballesteros-Merino, Guorong Xu, Adam Mark, Art Nasamran, J Silvio Gutkind, Kathleen M Fisch and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancers, 2023. 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
0.5field-weighted citation impact, top 33% 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

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  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

15 authors at 4 institutions in 2 countries.

Jesse R QualliotineDepartment of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, CA 92093, USA.ORCID 0000-0002-7040-9069
Takuya NakagawaGleiberman Head and Neck Cancer Center, Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.ORCID 0000-0003-1216-4822
Sara Brin RosenthalCenter for Computational Biology and Bioinformatics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Sayed SadatGleiberman Head and Neck Cancer Center, Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.
Carmen Ballesteros-MerinoEarle A. Chiles Research Institute, Providence Cancer Center, Portland, OR 97213, USA.
Guorong XuCenter for Computational Biology and Bioinformatics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Adam MarkCenter for Computational Biology and Bioinformatics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Art NasamranCenter for Computational Biology and Bioinformatics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
J Silvio GutkindGleiberman Head and Neck Cancer Center, Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.
Kathleen M FischCenter for Computational Biology and Bioinformatics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Theresa GuoDepartment of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, CA 92093, USA.ORCID 0000-0002-1689-3275
Bernard A FoxEarle A. Chiles Research Institute, Providence Cancer Center, Portland, OR 97213, USA.
Zubair KhanDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, MD 21218, USA.
Alfredo A MolinoloGleiberman Head and Neck Cancer Center, Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.
Joseph A CalifanoDepartment of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, CA 92093, USA.
University of California San Diego · USProvidence Portland Medical Center · USChiba University · JPJohns Hopkins University · US

Funding

UC San Diego Clinical and Translational Research InstituteUL1TR001442 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, HOGARTH, MICHAEL · 2015 to 2024
$88.3M
OTOLARYNGOLOGY TRAINING IN IMMUN., VIROL. &MOLEC. BIOL.T32DC000028 · NIDCD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RYAN, ALLEN F. · 1989 to 2020
$2.1M
NCATS NIH HHS UL1 TR001442NIDCD NIH HHS T32 DC000028
6 · The paper itself

Abstract

HPV-associated oropharynx carcinoma (HPVOPC) tumors have a relatively low mutational burden. Elucidating the relative contributions of other tumor alterations, such as DNA methylation alterations, alternative splicing events (ASE), and copy number variation (CNV), could provide a deeper understanding of carcinogenesis drivers in this disease. We applied network propagation analysis to multiple classes of tumor alterations in a discovery cohort of 46 primary HPVOPC tumors and 25 cancer-unaffected controls and validated our findings with TCGA data. We identified significant overlap between differential gene expression networks and all alteration classes, and this association was highest for methylation and lowest for CNV. Significant overlap was seen for gene clusters of G protein-coupled receptor (GPCR) pathways. HPV16-human protein interaction analysis identified an enriched cluster defined by an immune-mediated GPCR signal, including CXCR3 cytokines CXCL9, CXCL10, and CXCL11. CXCR3 was found to be expressed in primary HPVOPC, and scRNA-seq analysis demonstrated CXCR3 ligands to be highly expressed in M2 macrophages. In vivo models demonstrated decreased tumor growth with antagonism of the CXCR3 receptor in immunodeficient but not immunocompetent mice, suggesting that the CXCR3 axis can drive tumor proliferation in an autocrine fashion, but the effect is tempered by an intact immune system. In conclusion, methylation, ASE, and SNV alterations are highly associated with network gene expression changes in HPVOPC, suggesting that ASE and methylation alterations have an important role in driving the oncogenic phenotype. Network analysis identifies GPCR networks, specifically the CXCR3 chemokine axis, as modulators of tumor-immune interactions that may have proliferative effects on primary tumors as well as a role for immunosurveillance; however, CXCR3 inhibition should be used with caution, as these agents may both inhibit and stimulate tumor growth considering the competing effects of this cytokine axis. Further investigation is needed to explore opportunities for targeted therapy in this setting.

Indexed as

epigeneticsexome sequencinghead and neck squamous cell carcinomaHPVhuman papillomavirusnetwork analysisoropharyngeal neoplasmsThe Cancer Genome Atlas (TCGA)

Identifiers

PMID37686653
PMCPMC10486378
OpenAlexW4386369860

What OpenQuestion holds

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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.