Abstract
BackgroundHigh-grade serous ovarian carcinoma is highly heterogeneous, and although many studies have been conducted to identify high-grade serous ovarian carcinoma molecular subtypes that are sensitive to immunotherapy, no precise molecular subtype has been proposed to date. Immune cell infiltration and immune checkpoints are highly correlated with immunotherapy. Here, we investigated immune cell infiltration and immune checkpoint values for prognosis and precise immunotherapy for high-grade serous ovarian carcinoma based on molecular subtype classification.Results“High antigen-presenting cells infiltration molecular subtype of high-grade serous ovarian carcinoma” was identified in immune cell infiltration profiles. Each of the three immune cell infiltration clusters (A, B, and C) demonstrated distinct immune cell characterization, with immune cell infiltration cluster C exhibiting high antigen-presenting cell infiltration, improved prognosis, and higher sensitivity to immunotherapy. Programmed death-1/programmed death ligand 1 has a prognostic and predictive role that can help classify molecular subtypes.ConclusionsOur findings redefined a unique molecular subtype of high-grade serous ovarian carcinoma, suggesting that high-grade serous ovarian carcinoma patients with higher antigen-presenting cell infiltration and programmed death-1/programmed death ligand 1 expression can benefit from precise immunotherapy.
Highlights
High-grade serous ovarian carcinoma is highly heterogeneous, and many studies have been conducted to identify high-grade serous ovarian carcinoma molecular subtypes that are sensitive to immunotherapy, no precise molecular subtype has been proposed to date
PD‐1 and PD‐L1 were associated with improved outcomes in High-grade serous ovarian carcinoma (HGSOC) To investigate whether Programmed death1 (PD-1)/Programmed death ligand 1 (PD-L1) expression was related to clinical prognosis, clinical information was extracted from four databases, including three HGSOC databases: GSE53963 (GSE53963-HGSOC), GSE135820 (GSE135820-HGSOC), and GSE32062 (GSE32062HGSOC) and The Cancer General Atlas (TCGA) database of Ovarian carcinoma (OC) (TCGA-OC)
The higher PD-1/PD-L1 expression group had significantly better overall survival (OS) in the three HGSOC databases compared with the lower expression group (p = 0.023 for PD-1 and p = 0.021 for PD-L1 in GSE5396, p = 0.016 for PD-1 and p = 0.026 for PD-L1 in GSE32062, p < 0.001 for PD-1 and p < 0.001 for PD-L1 in GSE135820, log-rank test; Fig. 1A–C)
Summary
High-grade serous ovarian carcinoma is highly heterogeneous, and many studies have been conducted to identify high-grade serous ovarian carcinoma molecular subtypes that are sensitive to immunotherapy, no precise molecular subtype has been proposed to date. Immune cell infiltration and immune checkpoints are highly correlated with immunotherapy. We investigated immune cell infiltration and immune checkpoint values for prognosis and precise immunotherapy for high-grade serous ovarian carcinoma based on molecular subtype classification. High-grade serous ovarian carcinoma (HGSOC) is mainly diagnosed at advanced stages (III/IV) with a 5-year survival rate of 45.6% and accounts for 90% of EOC cases [2, 3]. High heterogeneity and resistance to platinum chemotherapy significantly contribute to the poor prognosis of HGSOC [4]. Precise molecular treatment has proved effective and safe against gynecological malignant tumors, such as breast ductal carcinoma and endometrial carcinoma. The precise molecular classification of tumors contributed to treatment benefits, with the 5-year disease-free survival of breast ductal carcinoma luminal A and B subtypes being significantly higher than
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