Autoantibodies against HSF1 and CCDC155 as biomarkers of early-Stage, high-Grade serous ovarian cancer

Amy L. Wilson, Laura R. Moffitt, Nadine Duffield, Adam Rainczuk, Tom W. Jobling, Magdalena Plebanski, Andrew N. Stephens

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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 high-grade serous ovarian cancers (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 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.

Original languageEnglish
Pages (from-to)183-192
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Volume27
Issue number2
DOIs
Publication statusPublished - 1 Feb 2018

Cite this

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title = "Autoantibodies against HSF1 and CCDC155 as biomarkers of early-Stage, high-Grade serous ovarian cancer",
abstract = "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 high-grade serous ovarian cancers (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 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.",
author = "Wilson, {Amy L.} and Moffitt, {Laura R.} and Nadine Duffield and Adam Rainczuk and Jobling, {Tom W.} and Magdalena Plebanski and Stephens, {Andrew N.}",
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Autoantibodies against HSF1 and CCDC155 as biomarkers of early-Stage, high-Grade serous ovarian cancer. / Wilson, Amy L.; Moffitt, Laura R.; Duffield, Nadine; Rainczuk, Adam; Jobling, Tom W.; Plebanski, Magdalena; Stephens, Andrew N.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 27, No. 2, 01.02.2018, p. 183-192.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Autoantibodies against HSF1 and CCDC155 as biomarkers of early-Stage, high-Grade serous ovarian cancer

AU - Wilson, Amy L.

AU - Moffitt, Laura R.

AU - Duffield, Nadine

AU - Rainczuk, Adam

AU - Jobling, Tom W.

AU - Plebanski, Magdalena

AU - Stephens, Andrew N.

PY - 2018/2/1

Y1 - 2018/2/1

N2 - 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 high-grade serous ovarian cancers (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 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.

AB - 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 high-grade serous ovarian cancers (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 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.

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