Short telomere length in peripheral blood leukocyte predicts poor prognosis and indicates an immunosuppressive phenotype in gastric cancer patients.

Abstract

Compelling evidences indicate that relative telomere length (RTL) in peripheral blood leukocytes (PBLs) can predict the clinical outcome of several cancers. However, to date, the prognostic value of leukocyte RTL in gastric cancer (GC) patients has not been explored. In this study, relative telomere length (RTL) in peripheral blood leukocytes (PBLs) was measured using a real-time PCR-based method in a total of 693 GC patients receiving surgical resection. The prognostic value of leukocyte RTL was first explored in the training set (112 patients) using Kaplan-Meier and Cox proportional hazards regression analyses. Then an independent cohort of 581 patients was used as a validation set. To explore potential mechanism, we detected the immunophenotypes of peripheral blood mononuclear cells and plasma concentrations of several cytokines in GC patients. Patients with short RTL showed significantly worse overall survival (OS) and relapse-free survival (RFS) than those with long RTL in all patient sets. Furthermore, leukocyte RTL and TNM stage exhibited a notable joint effect in prognosis prediction. Integration of TNM stage and leukocyte RTL significantly improved the prognosis prediction efficacy for GC. In addition, we found that patients with short RTL had a higher CD4(+) T cell percentage in PBMCs, CD19(+)IL-10(+) Breg percentage in B cells and plasma IL-10 concentration, indicating an enhanced immunosuppressive status with short leukocyte RTL. In conclusion, our study for the first time demonstrates that leukocyte RTL is an independent prognostic marker complementing TNM stage and associated with an immunosuppressive phenotype in the peripheral blood lymphocytes in GC patients.