Autoantibodies against HSF1 and CCDC155 as Biomarkers of Early-Stage, High-Grade Serous Ovarian Cancer

Cancer Epidemiol Biomarkers Prev. 2018 Feb;27(2):183-192. doi: 10.1158/1055-9965.EPI-17-0752. Epub 2017 Nov 15.


Background: Tumor-directed circulating autoantibodies (AAb) are a well-established feature of many solid tumor types, and are often observed prior to clinical disease manifestation. As such, they may provide a good indicator of early disease development. We have conducted a pilot study to identify novel AAbs as markers of early-stage HGSOCs.Methods: A rare cohort of patients with early (FIGO stage Ia-c) HGSOCs for IgG, IgA, and IgM-mediated AAb reactivity using high-content protein arrays (containing 9,184 individual proteins). AAb reactivity against selected antigens was validated by ELISA in a second, independent cohort of individual patients.Results: A total of 184 antigens were differentially detected in early-stage HGSOC patients compared with all other patient groups assessed. Among the six most highly detected "early-stage" antigens, anti-IgA AAbs against HSF1 and anti-IgG AAbs CCDC155 (KASH5; nesprin 5) were significantly elevated in patients with early-stage malignancy. Receiver operating characteristic (ROC) analysis suggested that AAbs against HSF1 provided better detection of early-stage malignancy than CA125 alone. Combined measurement of anti-HSF1, anti-CCDC155, and CA125 also improved efficacy at higher sensitivity.Conclusions: The combined measurement of anti-HSF1, anti-CCDC155, and CA125 may be useful for early-stage HGSOC detection.Impact: This is the first study to specifically identify AAbs associated with early-stage HGSOC. The presence and high frequency of specific AAbs in early-stage cancer patients warrants a larger scale examination to define their value for early disease detection at primary diagnosis and/or recurrence. Cancer Epidemiol Biomarkers Prev; 27(2); 183-92. ©2017 AACR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Biomarkers, Tumor / blood
  • CA-125 Antigen / blood
  • CA-125 Antigen / immunology*
  • Case-Control Studies
  • Cell Cycle Proteins / immunology*
  • Cystadenofibroma / blood
  • Cystadenofibroma / diagnosis*
  • Cystadenofibroma / immunology
  • Cystadenofibroma / pathology
  • Cystadenoma, Papillary / blood
  • Cystadenoma, Papillary / diagnosis*
  • Cystadenoma, Papillary / immunology
  • Cystadenoma, Papillary / pathology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Heat Shock Transcription Factors / immunology*
  • Humans
  • Neoplasm Staging
  • Nuclear Proteins / immunology*
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / pathology
  • Pilot Projects
  • Prospective Studies
  • ROC Curve


  • Autoantibodies
  • Biomarkers, Tumor
  • CA-125 Antigen
  • Cell Cycle Proteins
  • HSF1 protein, human
  • Heat Shock Transcription Factors
  • KASH5 protein, human
  • Nuclear Proteins