American Association for Cancer Research
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Table S2 from The Oxford Classic Links Epithelial-to-Mesenchymal Transition to Immunosuppression in Poor Prognosis Ovarian Cancers

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posted on 2023-03-31, 22:23 authored by Zhiyuan Hu, Paula Cunnea, Zhe Zhong, Haonan Lu, Oloruntoba I. Osagie, Leticia Campo, Mara Artibani, Katherine Nixon, Jennifer Ploski, Laura Santana Gonzalez, Abdulkhaliq Alsaadi, Nina Wietek, Stephen Damato, Sunanda Dhar, Sarah P. Blagden, Christopher Yau, Joanna Hester, Ashwag Albukhari, Eric O. Aboagye, Christina Fotopoulou, Ahmed Ahmed

Table S2. The QuPath classification results for the immunohistochemistry of CAPS in SOC tissue microarrays.

Funding

Ovarian Cancer Action

Cancer Research UK Oxford Centre

Cancer Research UK

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Oxford Biomedical Research Centre

National Institute for Health Research

History

ARTICLE ABSTRACT

Using RNA sequencing, we recently developed the 52-gene–based Oxford classifier of carcinoma of the ovary (Oxford Classic, OxC) for molecular stratification of serous ovarian cancers (SOCs) based on the molecular profiles of their cell of origin in the fallopian tube epithelium. Here, we developed a 52-gene NanoString panel for the OxC to test the robustness of the classifier. We measured the expression of the 52 genes in an independent cohort of prospectively collected SOC samples (n = 150) from a homogenous cohort who were treated with maximal debulking surgery and chemotherapy. We performed data mining of published expression profiles of SOCs and validated the classifier results on tissue arrays comprising 137 SOCs. We found evidence of profound nongenetic heterogeneity in SOCs. Approximately 20% of SOCs were classified as epithelial-to-mesenchymal transition–high (EMT-high) tumors, which were associated with poor survival. This was independent of established prognostic factors, such as tumor stage, tumor grade, and residual disease after surgery (HR, 3.3; P = 0.02). Mining expression data of 593 patients revealed a significant association between the EMT scores of tumors and the estimated fraction of alternatively activated macrophages (M2; P < 0.0001), suggesting a mechanistic link between immunosuppression and poor prognosis in EMT-high tumors. The OxC-defined EMT-high SOCs carry particularly poor prognosis independent of established clinical parameters. These tumors are associated with high frequency of immunosuppressive macrophages, suggesting a potential therapeutic target to improve clinical outcome.