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Posttranslational modifications induce autoantibodies with risk prediction capability in patients with small cell lung cancer.
Tuesday,2023-02-28 15:09 America/Los_Angeles — ecterry
| Title | Posttranslational modifications induce autoantibodies with risk prediction capability in patients with small cell lung cancer. |
| Publication Type | Journal Article |
| Year of Publication | 2023 |
| Authors | Lastwika, KJ, Kunihiro, A, Solan, JL, Zhang, Y, Taverne, LR, Shelley, D, Rho, J-H, Randolph, TW, Li, CI, Grogan, EL, Massion, PP, Fitzpatrick, AL, MacPherson, D, A Houghton, MG, Lampe, PD |
| Journal | Sci Transl Med |
| Volume | 15 |
| Issue | 678 |
| Pagination | eadd8469 |
| Date Published | 2023 Jan 11 |
| ISSN | 1946-6242 |
| Keywords | Autoantibodies, Humans, Lung Neoplasms, Protein Processing, Post-Translational, Small Cell Lung Carcinoma |
| Abstract | <p>Small cell lung cancer (SCLC) elicits the generation of autoantibodies that result in unique paraneoplastic neurological syndromes. The mechanistic basis for the formation of such autoantibodies is largely unknown but is key to understanding their etiology. We developed a high-dimensional technique that enables detection of autoantibodies in complex with native antigens directly from patient plasma. Here, we used our platform to screen 1009 human plasma samples for 3600 autoantibody-antigen complexes, finding that plasma from patients with SCLC harbors, on average, fourfold higher disease-specific autoantibody signals compared with plasma from patients with other cancers. Across three independent SCLC cohorts, we identified a set of common but previously unknown autoantibodies that are produced in response to both intracellular and extracellular tumor antigens. We further characterized several disease-specific posttranslational modifications within extracellular proteins targeted by these autoantibodies, including citrullination, isoaspartylation, and cancer-specific glycosylation. Because most patients with SCLC have metastatic disease at diagnosis, we queried whether these autoantibodies could be used for SCLC early detection. We created a risk prediction model using five autoantibodies with an average area under the curve of 0.84 for the three cohorts that improved to 0.96 by incorporating cigarette smoke consumption in pack years. Together, our findings provide an innovative approach to identify circulating autoantibodies in SCLC with mechanistic insight into disease-specific immunogenicity and clinical utility.</p> |
| DOI | 10.1126/scitranslmed.add8469 |
| Alternate Journal | Sci Transl Med |
| PubMed ID | 36630482 |
| Grant List | P50 CA228944 / CA / NCI NIH HHS / United States R01 CA243328 / CA / NCI NIH HHS / United States P30 CA015704 / CA / NCI NIH HHS / United States KL2 TR002317 / TR / NCATS NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States HHSN268201800001C / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States 75N92021D00006 / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States U01 HL130114 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States |
ePub date:
23/01