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

Ann Surg Oncol. 2020 Oct;27(10):4035-4043. doi: 10.1245/s10434-020-08375-z. Epub 2020 Mar 21.

Abstract

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.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Breast Neoplasms* / genetics
  • Humans
  • Prognosis
  • Programmed Cell Death 1 Receptor / genetics*
  • RNA, Messenger / genetics

Substances

  • Biomarkers, Tumor
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • RNA, Messenger