Circulating PD-1 mRNA in Peripheral Blood is a Potential Biomarker for Predicting Survival of Breast Cancer Patients

• Published in: Annals of surgical oncology Vol. 27; no. 10; pp. 4035 - 4043
• Main Authors: Noda, Miwa, Masuda, Takaaki, Ito, Shuhei, Tobo, Taro, Kitagawa, Akihiro, Hu, Qingjiang, Shimizu, Dai, Eguchi, Hidetoshi, Etoh, Tsuyoshi, Ohno, Shinji, Inomata, Masafumi, Mimori, Koshi
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.10.2020; Springer Nature B.V
• Subjects: Apoptosis; Biomarkers; Biomarkers, Tumor - genetics; Breast cancer; Breast Neoplasms - genetics; CD4 antigen; Cell death; Flow cytometry; Gene expression; Genomes; Humans; Lymphocytes T; Medical prognosis; Medicine; Medicine & Public Health; Oncology; PD-1 protein; Peripheral blood; Polymerase chain reaction; Prognosis; Programmed Cell Death 1 Receptor - genetics; RNA, Messenger - genetics; Surgery; Surgical Oncology; Survival analysis; Translational Research and Biomarkers
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-020-08375-z

Background Programmed cell death 1 (PD-1) inhibitors have shown significant therapeutic promise in various cancers. However, the clinical significance of PD-1 expression remains not fully understood. In this study, we evaluated the clinical and prognostic relevance of PD-1 expression in breast cancer (BC). Methods First, we analyzed PD - 1 mRNA expression in BC tissues and performed a survival analysis using a dataset from The Cancer Genome Atlas. Next, we measured PD - 1 mRNA expression in peripheral blood (PB) in BC patients by quantitative reverse-transcription polymerase chain reaction. We performed a survival analysis and evaluated the association between PD - 1 mRNA expression in PB and the clinicopathological features of 372 BC patients who underwent curative resection. Flow cytometry (FCM) analysis was performed to identify PD-1-expressing cells in PB. Finally, we determined whether there was a correlation of PD - 1 mRNA expression in PB and tumor tissue. Results PD - 1 mRNA expression was significantly higher in tumor tissues compared with normal tissues. Decreased PD - 1 mRNA expression in tumor tissue was associated with poor overall survival (OS). PD - 1 mRNA expression in PB of BC patients was higher than that of healthy volunteers, and increased PD - 1 mRNA expression in PB was associated with poor OS. FCM revealed that PD-1 was mostly expressed on T cells in PB, predominantly in CD4 + T cells. PD - 1 mRNA expression in PB was negatively correlated with PD - 1 mRNA expression in tumor tissue. Conclusion High expression of PD - 1 mRNA in preoperative PB could serve as an effective biomarker that indicates poor prognosis in BC.