title: Short leukocyte telomere length predicts poor prognosis and indicates altered immune functions in colorectal cancer patients.
abstract: BACKGROUND
  Numerous studies indicate that the leukocyte telomere length is associated with the risk of cancers, including colorectal cancer (CRC). However, the prognostic value of leukocyte telomere length in CRC patients has not been investigated.
  
  
  METHODS
  Relative telomere length (RTL) of peripheral blood leukocytes (PBLs) from 571 CRC patients receiving surgical resection was measured using a polymerase chain reaction-based method. The Cox proportional hazards ratio model and the Kaplan-Meier curve were used to estimate the association between RTL and the clinical outcome of CRC patients in the training set (90 patients) and the testing set (86 patients). Finally, an independent cohort of 395 patients was used as an external validation set. The immunophenotype of PBLs and the plasma concentration of several immune-related cytokines were determined by flow cytometry and enzyme-linked immunosorbent assay, respectively.
  
  
  RESULTS
  Patients with shorter RTL had significantly poorer overall survival and relapse-free survival than those with longer RTL in the training, testing and validation sets. Furthermore, leukocyte RTL and Tumor-Node-Metastasis (TNM) stage exhibited a significant joint effect in the prognosis prediction of combined CRC patients, indicating that patients with both short RTL and advanced stages had the worst prognosis, when compared with other subgroups. In addition, patients with short RTL showed the higher percentage of CD4(+) T cell and the lower percentage of B cell in peripheral blood mononuclear cells, as well as the lower concentration of plasma transforming growth factor-β1, suggesting a possibility that the immune functions changed with RTL alteration.
  
  
  CONCLUSIONS
  Our study for the first time demonstrates that leukocyte RTL is an independent prognostic marker complementing TNM stage and associated with the immune functions in CRC patients.
authors.affiliation: State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an.
authors.forename: F
authors.initials: F
authors.lastname: Qu
authors.affiliation: Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an.
authors.forename: X
authors.initials: X
authors.lastname: He
authors.affiliation: Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an.
authors.forename: G
authors.initials: G
authors.lastname: Bao
authors.affiliation: Deparment of Gastroenterology, Xijing Hospital of Digestive Disease, Fourth Military Medical University, Xi'an.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.affiliation: Pharmaceutical College, Henan University, Kaifeng, People's Republic of China.
authors.forename: S
authors.initials: S
authors.lastname: Wan
authors.affiliation: State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi'an. Electronic address: xingjinliang@163.com.
authors.forename: J
authors.initials: J
authors.lastname: Xing
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007962:Leukocytes / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D012307:Risk Factors; D016615:Telomere / Q000235:genetics; D059506:Telomere Shortening / Q000235:genetics* / Q000276:immunology
keywords: colorectal cancer; cytokine; immunophenotype; leukocyte relative telomere length; overall survival; relapse-free survival