A multi‐ethnic analysis of immune‐related gene expression signatures in patients with ovarian clear cell carcinoma

Valerie Heong, Tuan Z Tan, Maiko Miwa, Jieru Ye, Diana Lim, C Simon Herrington, Yasushi Iida, Mitsutake Yano, Masanori Yasuda, Natalie Yl Ngoi, Sb Justin Wong, Aikou Okamoto, Charlie Gourley, Kosei Hasegawa, David Sp Tan, Ruby Yj Huang

Research output: Contribution to journalArticlepeer-review

Abstract

Little is known about the immune environment of ovarian clear cell carcinoma (OCCC) and its impact on various ethnic backgrounds. The aim of this OCCC immune-related gene expression signatures (irGES) study was to address the interaction between tumour and immune environment of ethnically-diverse Asian and Caucasian populations and to identify relevant molecular subsets of biological and clinical importance. Our study included 264 women from three different countries (Singapore, Japan, and UK) and identified four novel immune subtypes (PD1-high, CTLA4-high, antigen-presentation and pro-angiogenic subtype) with differentially expressed pathways, and gene ontologies using the NanoString nCounter PanCancer Immune Profiling Panel. The PD1-high and CTLA4-high subtypes demonstrated significantly higher PD1, PDL1 and CTLA4 expression and were associated with poorer clinical outcomes. Mismatch repair (MMR) protein expression, assessed by immunohistochemistry, revealed that about 5% of OCCC had deficient MMR expression. The prevalence was similar across the three countries and appeared to cluster in the CTLA4-high subtype. Our results suggest OCCC from women of Asian and Caucasian descent share significant clinical and molecular similarities. To our knowledge, our study is the first study to include both Asian and Caucasian women with OCCC and helps shine light on the impact of ethnic differences on the immune microenvironment of OCCC. This article is protected by copyright. All rights reserved.
Original languageEnglish
JournalThe Journal of Pathology
Early online date28 Jul 2021
DOIs
Publication statusE-pub ahead of print - 28 Jul 2021

Keywords

  • Ovarian cancer
  • RNA expression and ethnicity
  • clear cell cancer
  • gene expression signatures
  • immune micoenvironment
  • immune subtypes
  • microsatellite instability
  • mismatch repair protein

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