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Record W4387865430 · doi:10.1158/2767-9764.crc-23-0289

Cancer Relevance of Circulating Antibodies Against LINE-1 Antigens in Humans

2023· article· en· W4387865430 on OpenAlexfundno aff
Alexandra V. Vylegzhanina, Ivan A. Bespalov, Ksenia A. Novototskaya-Vlasova, Brandon M. Hall, Anatoli S. Gleiberman, Han Yu, Olga V. Leontieva, Katerina I. Leonova, Oleg V. Kurnasov, Andrei L. Osterman, Grace K. Dy, Alexey A. Komissarov, Elena Vasilieva, Jeff Gehlhausen, Akiko Iwasaki, Christine B. Ambrosone, Takemasa Tsuji, Junko Matsuzaki, Kunle Odunsi, Ekaterina L. Andrianova, Andrei V. Gudkov

Bibliographic record

VenueCancer Research Communications · 2023
Typearticle
Languageen
FieldAgricultural and Biological Sciences
TopicChromosomal and Genetic Variations
Canadian institutionsnot available
FundersNational Cancer InstituteNational Center for Advancing Translational SciencesYale UniversityUniversity of British ColumbiaRoswell Park Cancer Institute
KeywordsAntigenCarcinogenesisCancerImmune systemAutoantibodyAntibodyImmunologyBiologyRetrotransposonClinical significancePancreatic cancerCancer researchImmunoassayMedicinePathologyGeneticsGeneGenome

Abstract

fetched live from OpenAlex

Long interspersed nuclear element-1 (LINE-1 or L1), the most abundant family of autonomous retrotransposons occupying over 17% of human DNA, is epigenetically silenced in normal tissues by the mechanisms involving p53 but is frequently derepressed in cancer, suggesting that L1-encoded proteins may act as tumor-associated antigens recognized by the immune system. In this study, we established an immunoassay to detect circulating autoantibodies against L1 proteins in human blood. Using this assay in >2,800 individuals with or without cancer, we observed significantly higher IgG titers against L1-encoded ORF1p and ORF2p in patients with lung, pancreatic, ovarian, esophageal, and liver cancers than in healthy individuals. Remarkably, elevated levels of anti-ORF1p-reactive IgG were observed in patients with cancer with disease stages 1 and 2, indicating that the immune response to L1 antigens can occur in the early phases of carcinogenesis. We concluded that the antibody response against L1 antigens could contribute to the diagnosis and determination of immunoreactivity of tumors among cancer types that frequently escape early detection. SIGNIFICANCE: The discovery of autoantibodies against antigens encoded by L1 retrotransposons in patients with five poorly curable cancer types has potential implications for the detection of an ongoing carcinogenic process and tumor immunoreactivity.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.230
GPT teacher head0.435
Teacher spread0.204 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations10
Published2023
Admission routes1
Has abstractyes

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Same venueCancer Research CommunicationsSame topicChromosomal and Genetic VariationsFrench-language works237,207