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posted on 2023-03-31, 19:30 authored by Jayanta Chatterjee, Wei Dai, Nor Haslinda Abd Aziz, Pei Yun Teo, John Wahba, David L. Phelps, Christian J. Maine, Lynsey M. Whilding, Roberto Dina, Giorgia Trevisan, Kirsty J. Flower, Andrew J.T. George, Sadaf Ghaem-Maghami The stability of unsupervised hierarchical clustering of candidate biomarkers A: 23 markers in PBMC samples, B: 22 markers in ascites samples. Healthy controls (HH), benign ovarian tumours (BN), borderline ovarian tumour (BT) and malignant cases (SER: serous; END: endometrioid; CC: clear cell; MU: mucinous). The stability was estimated by pvclust package in R (see method).
Funding
Mann-Hodgson charitable trust and Rosie's charity
History
ARTICLE ABSTRACT
Purpose: We aimed to establish whether programmed cell death-1 (PD-1) and programmed cell death ligand 1 (PD-L1) expression, in ovarian cancer tumor tissue and blood, could be used as biomarkers for discrimination of tumor histology and prognosis of ovarian cancer.Experimental Design: Immune cells were separated from blood, ascites, and tumor tissue obtained from women with suspected ovarian cancer and studied for the differential expression of possible immune biomarkers using flow cytometry. PD-L1 expression on tumor-associated inflammatory cells was assessed by immunohistochemistry and tissue microarray. Plasma soluble PD-L1 was measured using sandwich ELISA. The relationships among immune markers were explored using hierarchical cluster analyses.Results: Biomarkers from the discovery cohort that associated with PD-L1+ cells were found. PD-L1+ CD14+ cells and PD-L1+ CD11c+ cells in the monocyte gate showed a distinct expression pattern when comparing benign tumors and epithelial ovarian cancers (EOCs)—confirmed in the validation cohort. Receiver operating characteristic curves showed PD-L1+ and PD-L1+ CD14+ cells in the monocyte gate performed better than the well-established tumor marker CA-125 alone. Plasma soluble PD-L1 was elevated in patients with EOC compared with healthy women and patients with benign ovarian tumors. Low total PD-1+ expression on lymphocytes was associated with improved survival.Conclusions: Differential expression of immunological markers relating to the PD-1/PD-L1 pathway in blood can be used as potential diagnostic and prognostic markers in EOC. These data have implications for the development and trial of anti–PD-1/PD-L1 therapy in ovarian cancer. Clin Cancer Res; 23(13); 3453–60. ©2016 AACR.
