Abstract

Background: Lymphocyte telomere length is strongly correlated with patient prognosis in several malignant tumor types and is thought to be related to tumor immunity. However, this correlation has not been studied in gynecological cancers. We determined the prognostic significance of peripheral blood lymphocyte telomere length in gynecologic cancers. Methods: Telomere length of lymphocytes from patients with gynecological malignant tumors (ovarian cancer (OC), N = 72; cervical cancer (CC), N = 63; endometrial cancer (EC), N = 87) was examined by quantitative reverse-transcription PCR of isolated mononuclear cells. Kaplan–Meier and Cox proportional hazard analyses were used to determine the association between lymphocyte telomere length and clinicopathological factors. Results: The overall survival (OS) and progression-free survival (PFS) of patients were based on the dichotomized lymphocyte telomere length using the median as a threshold (OC: 0.75, CC: 1.94, and EC: 1.09). A short telomere length was significantly correlated with residual tumors (≥1 cm) in OC and with advanced stage (III and IV) of CC. In OC and CC, patients with shorter relative lymphocyte telomere length (RLT) had significantly poorer OS and PFS than patients with longer RLT (p = 0.002, p = 0.003, and p = 0.001, p = 0.001, respectively). However, in EC, RLT was not significantly associated with OS or PFS (p = 0.567 and p = 0.304, log-rank test). Multivariate analysis showed that shorter RLT was a significant independent prognostic factor of PFS and OS for OC (p = 0.03 and p = 0.04, respectively) and CC (p = 0.02 and p = 0.03, respectively). Conclusions: Patients with OC and CC with shorter lymphocyte telomeres have significantly reduced survival; therefore, the peripheral blood lymphocyte telomere length is a prognostic biomarker in OC and CC.

Highlights

  • Telomeres, the terminal structures of chromosomes, are composed of long, repetitive 6-base pair nucleoproteins

  • (International Freedom of Gynecology and Obstetrics) stages (I, II, III, and IV) and lymphocyte telomere length was significantly higher in patients with advanced stages III and IV than early stages I and II (60.71% vs. 34.09% in ovarian cancer (OC), p = 0.027; 77.77% vs. 33.33% in CC, p = 0.001; 75% vs. 38.80% in endometrial cancer (EC), p = 0.001)

  • The correlation of myometrial invasion and menopause with telomere length was evaluated in patients with EC, and no significant correlation was found; lymph vascular space and lymph node metastasis were both significantly correlated with relative lymphocyte telomere length (RLT) in patients with EC (p = 0.015; p = 0.008)

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Summary

Introduction

The terminal structures of chromosomes, are composed of long, repetitive 6-base pair nucleoproteins. Short telomeres in peripheral blood cell DNA are associated with an increased risk of various human malignant tumors [10,11] including ovarian cancer (OC) [12], bladder cancer [13], gastric adenocarcinoma [14], colorectal cancer [15], and pancreatic cancer [16]. Lymphocyte telomere length is strongly correlated with patient prognosis in several malignant tumor types and is thought to be related to tumor immunity. This correlation has not been studied in gynecological cancers. Methods: Telomere length of lymphocytes from patients with gynecological malignant tumors (ovarian cancer (OC), N = 72; cervical cancer (CC), N = 63; endometrial cancer (EC), N = 87) was examined by quantitative reverse-transcription PCR of isolated mononuclear cells.

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