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.

Prognostic relevance of telomere length and telomerase reverse transcriptase variant (rs2242652) on the multiple myeloma patients

“…In the present study among patients' group, there was significant association between stage of the disease and relative telomere length. This finding agrees with Qu et al who demonstrated that short leukocyte RTL predicts poor prognosis and associated with an immunosuppressive phenotype in the peripheral blood lymphocytes in gastric cancer patients. Also, Chen et al demonstrated that short leukocyte RTL is an independent bad prognostic marker and associated with the immune functions in colorectal cancer patients.…”

Association of telomere length in peripheral leukocytes with chronic hepatitis B and hepatocellular carcinoma

“…In some types of cancers, such as gastric and bladder cancer, shorter RTL in leukocytes was a risk factor of tumorigenesis, [12,13,21] while it was opposite in lung and colorectal cancer. [17,18] …”

“…Some findings showed that shorter telomere length not only increases the risk of gastric cancer, [12] but also decreases the survival rate of bladder cancer, [13] while in other epidemiologic investigates, longer telomere length was associated with the increased risk of cancers that were reported. [14–18] To date, little research has investigated the relationship between telomere length and the event of hepatocarcinogenesis (from normal, CHB to HCC) to our knowledge.…”

Leukocyte telomere length associates with nasopharyngeal carcinoma risk and survival in Hong Kong Chinese

“…Short rLTL predicts poor survival in colorectal, bladder and gastric cancers. [24][25][26] Long rLTL predicts poor survival in gliomas, prostate, and renal cell carcinomas. 23,27,42 However, this NPC study suggests for the first time that late Stage IV NPC patients with short or long, that is, suboptimal, blood telomere length associates with poor survival compared to those carrying medium rLTL.…”