TY - JOUR
T1 - Cancer Relevance of Circulating Antibodies Against LINE-1 Antigens in Humans
AU - Vylegzhanina, Alexandra V.
AU - Bespalov, Ivan A.
AU - Novototskaya-Vlasova, Ksenia A.
AU - Hall, Brandon M.
AU - Gleiberman, Anatoli S.
AU - Yu, Han
AU - Leontieva, Olga V.
AU - Leonova, Katerina I.
AU - Kurnasov, Oleg V.
AU - Osterman, Andrei L.
AU - Dy, Grace K.
AU - Komissarov, Alexey A.
AU - Vasilieva, Elena
AU - Gehlhausen, Jeff
AU - Iwasaki, Akiko
AU - Ambrosone, Christine B.
AU - Tsuji, Takemasa
AU - Matsuzaki, Junko
AU - Odunsi, Kunle
AU - Andrianova, Ekaterina L.
AU - Gudkov, Andrei V.
N1 - Publisher Copyright:
© 2023 The Authors.
PY - 2023/11
Y1 - 2023/11
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85195568345
U2 - 10.1158/2767-9764.CRC-23-0289
DO - 10.1158/2767-9764.CRC-23-0289
M3 - Article
C2 - 37870410
AN - SCOPUS:85195568345
SN - 2767-9764
VL - 3
SP - 2256
EP - 2267
JO - Cancer Research Communications
JF - Cancer Research Communications
IS - 11
ER -