Prognostic Value of Peripheral Blood Lymphocyte Telomere Length in Gynecologic Malignant Tumors

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.

Shorter Leukocyte Telomere Length Is Associated with Worse Survival of Patients with Bladder Cancer and Renal Cell Carcinoma

“…For instance, Svenson et al found that long leukocyte TL correlated with worse survival in breast cancer [58], ccRCC [59] and prostate cancer [60], which was also observed in hepatocellular carcinoma by Liu et al [61]. Other studies revealed that short leukocyte TL was associated with worse survival in BC [62], gastric cancer [63], colorectal cancer [64,65], ovarian cancer and cervical cancer [66]. Using GRS and MR approaches, Gao et al demonstrated that decreased leukocyte TL was associated with worse overall survival of patients with rectum adenocarcinoma, sarcoma and skin cutaneous melanoma, but better overall survival of patients with papillary RCC [76].…”

“…Several studies suggest that a higher proliferation rate of immune cells accounts for the association of shorter TL with poorer overall survival. One mechanism could involve regulation of telomere length by regulating telomerase activity via serum factors such as cytokine TGFß1 [65] or interleukins [66], which are known to be regulators of telomerase [99,100]. For instance, a lower concentration of plasma transforming growth factor-β1 (TGF-β1) was correlated with shorter TL in CD4 + T cells [65].…”

“…In support of this, Haycock et al conducted a Mendelian randomization (MR) study, which showed that increased telomere length (TL) due to germline genetic variation was significantly associated with a higher risk of developing cancer, including BC (OR 2.19 [1.32-3.66]) and RCC (OR 1.55 [1.08-2.23]) [57]. Interestingly, recent studies also revealed that the TL of PBL cells has prognostic potential to predict survival of patients with various types of solid cancers [58][59][60][61][62][63][64][65][66]. However, inconsistent results were reported for distinct cancer types, both in the context of cancer risk assessment and survival prognosis; while some studies reported that longer PBL TL correlated with worse survival, i.e., in breast cancer [58], clear cell RCC [59], prostate cancer [60], and hepatocellular carcinoma [61], other reports indicated that shorter PBL TL correlated with worse survival in BC [62], gastric cancer [63], colorectal cancer [64,65], ovarian cancer and cervical cancer [66].…”

“…Interestingly, recent studies also revealed that the TL of PBL cells has prognostic potential to predict survival of patients with various types of solid cancers [58][59][60][61][62][63][64][65][66]. However, inconsistent results were reported for distinct cancer types, both in the context of cancer risk assessment and survival prognosis; while some studies reported that longer PBL TL correlated with worse survival, i.e., in breast cancer [58], clear cell RCC [59], prostate cancer [60], and hepatocellular carcinoma [61], other reports indicated that shorter PBL TL correlated with worse survival in BC [62], gastric cancer [63], colorectal cancer [64,65], ovarian cancer and cervical cancer [66]. Importantly, it was shown that long and heterogeneous TL in blood lymphocytes indicated increased BC risk [67], while another study observed shorter PBL TL in BC patients [68].…”

Identification of a Prognosis-Related Risk Signature for Bladder Cancer to Predict Survival and Immune Landscapes

“…Interferon- γ , secreted by CD8+ cytotoxic T lymphocytes, inhibits tumors, an essential part of antitumor immune responses [ 78 ]. IFN- α expands CD8+ T cells on a large scale and blocks the cycle of cancer cells, thereby improving outcomes [ 79 ]. In our study, the expression of TNFRSF14 is positively correlated with the expression levels of MHC-I, MHC-II, LCK, and interferon, while the risk score was the opposite.…”