Journal
JOURNAL OF PATHOLOGY
Volume 255, Issue 3, Pages 285-295Publisher
WILEY
DOI: 10.1002/path.5769
Keywords
ovarian cancer; clear cell cancer; gene expression signatures; immune microenvironment; microsatellite instability; mismatch repair protein; immune subtypes; RNA expression and ethnicity
Funding
- National Medical Research Council (NMRC) Singapore
- National Research Foundation Singapore
- Singapore Ministry of Education under its Research Centres of Excellence initiative
- National University Cancer Centre of Singapore (NCIS) Research Grant, Theme: EMT in Cancer
- Yong Loo Lin fellowship grant
- NHG-LKC Medicine Clinician Scientist Career Scheme grant [CSCS/20001]
- Nicola Murray Foundation
- Singapore Ministry of Health's National Medical Research Council [NMRC/TA/0019/2013, NMR/CSA-INV/0016/2017]
- Ministry of Education, Taiwan [NTU-109V0402]
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This study investigated the immune environment of ovarian clear cell carcinoma (OCCC) in ethnically diverse populations and identified four novel immune subtypes with differentially expressed pathways. The PD1-high and CTLA4-high subtypes were associated with poorer clinical outcomes. Deficient Mismatch repair (MMR) protein expression was found in about 5% of OCCCs, clustering in the CTLA4-high subtype. The study highlights significant clinical and molecular similarities between OCCC in women of Asian and Caucasian descent.
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 the 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 OCCCs had deficient MMR expression. The prevalence was similar across the three countries and appeared to cluster in the CTLA4-high subtype. Our results suggest that OCCC from women of Asian and Caucasian descent shares 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 to shine light on the impact of ethnic differences on the immune microenvironment of OCCC. (c) 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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