Evidence map›Paper›PMID 33055416›Full record

ArticleJCI insight2020

Proteomic approach to discover human cancer viruses from formalin-fixed tissues.

Tuna Toptan, Pamela S Cantrell, Xuemei Zeng, Yang Liu, Mai Sun, Nathan A Yates, Yuan Chang, Patrick S Moore

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.2field-weighted citation impact, top 46% 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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. Review
  3. 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

8 authors at 4 institutions in 3 countries.

Tuna ToptanHillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Pamela S CantrellBiomedical Mass Spectrometry Center and.
Xuemei ZengBiomedical Mass Spectrometry Center and.
Yang LiuBiomedical Mass Spectrometry Center and.
Mai SunBiomedical Mass Spectrometry Center and.
Nathan A YatesBiomedical Mass Spectrometry Center and.
Yuan ChangHillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Patrick S MooreHillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
IONICS Mass Spectrometry (Canada) · CAUPMC Hillman Cancer Center · USGoethe University Frankfurt · DEUniversity of Pittsburgh · US

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHRISTOPHER J. BAKKENIST · 1988 to 2026
$158.0M
Therapuetic Immune Targeting of EphA2 Expressed by Melanoma & Its Tumor-AssociateP50CA121973 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KIRKWOOD, JOHN MUNN · 2008 to 2018
$22.9M
Discovery and Characterization of New Human Cancer VirusesR35CA197463 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MOORE, PATRICK S. · 2016 to 2022
$6.2M
Role of a Novel Mitotic 4E-BP1 Protein Isoform in Cellular TransformationR01CA232604 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHANG, YUAN · 2019 to 2023
$1.7M
Transcriptomic and Proteomic Approaches to Discovering Viral Causes for Human HemR01CA170354 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHANG, YUAN · 2012 to 2015
$1.3M
NCI NIH HHS P30 CA047904NCI NIH HHS P50 CA121973NCI NIH HHS R01 CA170354NCI NIH HHS R01 CA232604NCI NIH HHS R35 CA197463
6 · The paper itself

Abstract

The challenge of discovering a completely new human tumor virus of unknown phylogeny or sequence depends on detecting viral molecules and differentiating them from host molecules in the virus-associated neoplasm. We developed differential peptide subtraction (DPS) using differential mass spectrometry (dMS) followed by targeted analysis to facilitate this discovery. We validated this approach by analyzing Merkel cell carcinoma (MCC), an aggressive human neoplasm, in which ~80% of cases are caused by the human Merkel cell polyomavirus (MCV). Approximately 20% of MCC have a high mutational burden and are negative for MCV, but are microscopically indistinguishable from virus positive cases. Using 23 (12 MCV+, 11 MCV-) formalin-fixed MCC, DPS identified both viral and human biomarkers (MCV large T antigen, CDKN2AIP, SERPINB5, and TRIM29) that discriminate MCV+ and MCV- MCC. Statistical analysis of 498,131 dMS features not matching the human proteome by DPS revealed 562 (0.11%) to be upregulated in virus-infected samples. Remarkably, 4 (20%) of the top 20 candidate MS spectra originated from MCV T oncoprotein peptides and confirmed by reverse translation degenerate oligonucleotide sequencing. DPS is a robust proteomic approach to identify potentially novel viral sequences in infectious tumors when nucleic acid-based methods are not feasible.

Indexed as

Antigens, Viral, TumorBiomarkersCarcinoma, Merkel CellFormaldehydeHumansMerkel cell polyomavirusPolyomavirus InfectionsProteomeSkin NeoplasmsTumor Virus InfectionsAntigens, Viral, TumorBiomarkersFormaldehydeProteomeCancerProteomicsVirology

Identifiers

PMID33055416
PMCPMC7710300
OpenAlexW3093063563

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.