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A multi‐ethnic analysis of immune‐related gene expression signatures in patients with ovarian clear cell carcinoma
Author(s) -
Heong Valerie,
Tan Tuan Z,
Miwa Maiko,
Ye Jieru,
Lim Diana,
Herrington C Simon,
Iida Yasushi,
Yano Mitsutake,
Yasuda Masanori,
Ngoi Natalie YL,
Wong SB Justin,
Okamoto Aikou,
Gourley Charlie,
Hasegawa Kosei,
Tan David SP,
Huang Ruby YJ
Publication year - 2021
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.5769
Subject(s) - immune system , ethnic group , clear cell carcinoma , medicine , ovarian cancer , oncology , immunohistochemistry , cancer , immunology , political science , law
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. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.