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Background <p>HGSOC is the leading cause of death among all gynaecological malignancies. We recently identified that genomically unstable cancers that display high levels of chromosomal instability, including HGSOC, rely on a cGAS/STING/IL-6R autocrine loop for survival. Here, we determined the prevalence of IL-6R expression in HGSOC samples to identify patients that could potentially benefit from treatment inhibiting IL-6R.</p> Methods <p>Immunohistochemical staining of IL-6R and STING in a well-characterized cohort of advanced-stage HGSOC patients (<i>N</i> = 268) was digitally quantified. After excluding patients with less than two cores or an “<i>unknown</i>” alive status, the resulting data of 230 patients was correlated with overall survival, and relevant histopathological, clinical, genetic, and therapeutic variables were assessed.</p> Results <p>The majority of patient cores were positive for IL-6R and STING, where the staining intensity for IL-6R was more varied, while STING had a more consistent expression. We found that IL-6R expression is associated with improved survival. Multivariate analyses also identified that IL-6R, BRCA1/BRCA2 mutation, primary treatment, and surgical outcome are strong independent prognostic factors of overall survival.</p> Conclusions <p>Our findings suggest that ~37% of HGSOC patients might benefit from treatment targeting IL-6R. The high prevalence and underlying molecular data warrant further investigation in a clinical trial.</p>

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IL-6R expression is an independent prognostic factor in high-grade serous ovarian cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月8日

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  • Alexis M. Maagdenberg,
  • Annegé Vledder,
  • Sterre T. Paijens,
  • Annechien Plat,
  • Floris Foijer,
  • Hans W. Nijman,
  • Marco de Bruyn

摘要

Background

HGSOC is the leading cause of death among all gynaecological malignancies. We recently identified that genomically unstable cancers that display high levels of chromosomal instability, including HGSOC, rely on a cGAS/STING/IL-6R autocrine loop for survival. Here, we determined the prevalence of IL-6R expression in HGSOC samples to identify patients that could potentially benefit from treatment inhibiting IL-6R.

Methods

Immunohistochemical staining of IL-6R and STING in a well-characterized cohort of advanced-stage HGSOC patients (N = 268) was digitally quantified. After excluding patients with less than two cores or an “unknown” alive status, the resulting data of 230 patients was correlated with overall survival, and relevant histopathological, clinical, genetic, and therapeutic variables were assessed.

Results

The majority of patient cores were positive for IL-6R and STING, where the staining intensity for IL-6R was more varied, while STING had a more consistent expression. We found that IL-6R expression is associated with improved survival. Multivariate analyses also identified that IL-6R, BRCA1/BRCA2 mutation, primary treatment, and surgical outcome are strong independent prognostic factors of overall survival.

Conclusions

Our findings suggest that ~37% of HGSOC patients might benefit from treatment targeting IL-6R. The high prevalence and underlying molecular data warrant further investigation in a clinical trial.