<p>Improved biomarkers of treatment response are needed for patients with high-grade serous ovarian cancer (HGSC). A challenge is substantial anatomical site-to-site variation in expression. We completed data-independent acquisition–mass spectrometry (DIA-MS) analysis of 404 fresh frozen and 78 formalin-fixed, paraffin-embedded HGSC tissue samples from the ovary (adnexal) and a common secondary site (omentum) in 11 patients. This was compared with mutation testing, gene expression, and whole-genome copy number profiling. Proteins with relatively stable intra- and variable inter-individual expression (<i>n</i> = 1651), included a 52-protein module reflecting interferon-mediated tissue inflammation, indicative of a cGAS-STING pathway cytosolic double-stranded (ds) DNA response. The dsDNA sensing/inflammation score was higher in the omentum compared with the ovary. Ovarian HGSC samples showed marked inter-individual differences in inflammatory and immune responses to DNA damage. Stable discriminative features of the HGSC proteome, a prerequisite for clinical predictive biomarkers, are detectable in ovary (adnexal) tissue samples.</p>

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Overcoming intra-tumoral heterogeneity for biomarker discovery in the high-grade serous ovarian cancer proteome

  • Srikanth S. Manda,
  • Maiken M. Espersen,
  • Cristina Mapagu,
  • Natalie Bouantoun,
  • Jessica Boros,
  • Yoke-Eng Chiew,
  • Sivatharsny Srirangan,
  • Swetansu Pattnaik,
  • Catherine J. Kennedy,
  • Alison H. Brand,
  • Dale W. Garsed,
  • Ahwan Pandey,
  • David D. L. Bowtell,
  • Natasha Lucas,
  • Dylan Xavier,
  • Sadia Mahboob,
  • Daniel Bucio-Noble,
  • Brett Tully,
  • Peter G. Hains,
  • Phillip J. Robinson,
  • Qing Zhong,
  • Roger Reddel,
  • Anna DeFazio,
  • Rosemary L. Balleine

摘要

Improved biomarkers of treatment response are needed for patients with high-grade serous ovarian cancer (HGSC). A challenge is substantial anatomical site-to-site variation in expression. We completed data-independent acquisition–mass spectrometry (DIA-MS) analysis of 404 fresh frozen and 78 formalin-fixed, paraffin-embedded HGSC tissue samples from the ovary (adnexal) and a common secondary site (omentum) in 11 patients. This was compared with mutation testing, gene expression, and whole-genome copy number profiling. Proteins with relatively stable intra- and variable inter-individual expression (n = 1651), included a 52-protein module reflecting interferon-mediated tissue inflammation, indicative of a cGAS-STING pathway cytosolic double-stranded (ds) DNA response. The dsDNA sensing/inflammation score was higher in the omentum compared with the ovary. Ovarian HGSC samples showed marked inter-individual differences in inflammatory and immune responses to DNA damage. Stable discriminative features of the HGSC proteome, a prerequisite for clinical predictive biomarkers, are detectable in ovary (adnexal) tissue samples.