The prognostic significance of hTERT overexpression in cancers

Wang, Kai; Wang, Rui-Ling; Liu, Jing; Zhou, Ji; Li, Xue; Hu, Wenwei; Jiang, Weijian; Hao, Ning-Bo

doi:10.1097/md.0000000000011794

Cited by 35 publications

(25 citation statements)

References 45 publications

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“…It can be speculated that accelerated telomere shortening in B12 deficient subjects might be counteracted by compensatory mechanism that activate telomerase, an enzyme that can prolong telomeres. In oncologic patients, the induction of telomerase is a common tumor escape mechanism [49]. In contrast, average RTL in individuals with high B12 is probably the result of an adequately functioning one-carbon metabolism.…”

Section: Discussionmentioning

confidence: 99%

Telomere length, vitamin B12 and mortality in persons undergoing coronary angiography: the Ludwigshafen risk and cardiovascular health study

Pusceddu

Herrmann

Kleber

et al. 2019

Aging

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Background: Vitamin B12 (B12) deficiency and excess are associated with increased risk of age-related-diseases and mortality. It has been suggested that high- and low-B12 concentrations link to increased mortality through accelerated genomic aging and inflammation. Evidence to support this is limited.Results: B12 was associated with all-cause-mortality, RTL and hsCRP in a non-linear fashion. The association between B12 and mortality was not independent, as it lost significance after adjustment for potential confounders. In the lowest-(LB12) and highest-(HB12) quartiles of B12 mortality was higher than in the mid-range (HR:LB12:1.23;CI95%:1.06-1.43; HR:HB12:1.24;CI95%:1.06-1.44). We divided subjects with LB12 in quartiles of their RTL. Those with the longest-telomeres had a lower mortality-rate (HR:0.57;95%CI:0.39-0.83) and lower homocysteine than those with the shortest-telomeres. Amongst subjects with HB12, those with long-telomeres also had a lower mortality than those with short-telomeres (HR:0.40;95%CI:0.27-0.59). IL-6 and hsCRP concentrations were low in HB12LT but were high in HB12ST.Methods: B12, homocysteine, telomere length (RTL), interleukin-6 (IL-6) and high-sensitive-C-reactive-protein (hsCRP) were measured in 2970 participants of the LURIC study.Conclusions: Mortality, stratified according to B12 and RTL, seems to be driven by different mechanisms. In LB12 and HB12 subjects, mortality and accelerated telomere shortening might be driven by homocysteine and inflammation, respectively.

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Section: Discussionmentioning

confidence: 99%

Telomere length, vitamin B12 and mortality in persons undergoing coronary angiography: the Ludwigshafen risk and cardiovascular health study

Pusceddu

Herrmann

Kleber

et al. 2019

Aging

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“…Others have reported similar findings. Elevated expression of hTERT was associated with a poor prognosis in solid tumors such as gastric, lung, cervical, head and neck, breast, and ovarian cancer, and glioblastoma [ 24 , 25 ]. In head and neck cancer patients, elevated hTERT expression was associated with a higher recurrence rate ( p =0.044) and a lower 5-year survival rate ( p =0.011) [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-Based Cancer Mortality Risk Scoring System and hTERT Expression in Early-Stage Oral Squamous Cell Carcinoma

Yoon

Santella

Wang

et al. 2021

Journal of Oncology

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We have previously constructed a novel microRNA (miRNA)-based prognostic model and cancer-specific mortality risk score formula to predict survival outcome in oral squamous cell carcinoma (OSCC) patients who are already categorized into “early-stage” by the TNM staging system. A total of 836 early-stage OSCC patients were assigned the mortality risk scores. We evaluated the efficacy of various treatment regimens in terms of survival benefit compared to surgery only in patients stratified into high (risk score ≥0) versus low (risk score <0) mortality risk categories. For the high-risk group, surgery with neck dissection significantly improved the 5-year survival to 75% from 46% with surgery only ( p < 0.001 ); a Cox proportional hazard model on time-to-death demonstrated a hazard ratio of 0.37 for surgery with neck dissection (95% CI: 0.2–0.6; p = 0.0005 ). For the low-risk group, surgery only was the treatment of choice associated with 5-year survival benefit. Regardless of treatment selected, those with risk score ≥2 may benefit from additional therapy to prevent cancer relapse. We also identified hTERT (human telomerase reverse transcriptase) as a gene target common to the prognostic miRNAs. There was 22-fold increase in the hTERT expression level in patients with risk score ≥2 compared to healthy controls ( p < 0.0005 ). Overexpression of hTERT was also observed in the patient-derived OSCC organoid compared to that of normal organoid. The DNA cancer vaccine that targets hTERT-expressing cells currently undergoing rigorous clinical evaluation for other tumors can be repurposed to prevent cancer recurrence in these high-risk early-stage oral cancer patients.

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“…Telomerase activity enables cells to overcome replicative crisis or senescence and thus provides the cell with the capacity to divide infinitely [72,73,74,75]. The basic molecular mechanisms of telomerase activity are highly conserved throughout evolution and our understanding of the holoenzyme complex is steadily improving since its discovery by Blackburn and Greider in 1985.…”

Section: Telomerase Activationmentioning

confidence: 99%

Telomere Maintenance in Pediatric Cancer

Ackermann

Fischer

2019

IJMS

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Telomere length has been proposed as a biomarker of biological age and a risk factor for age-related diseases and cancer. Substantial progress has been made in recent decades in understanding the complex molecular relationships in this research field. However, the majority of telomere studies have been conducted in adults. The data on telomere dynamics in pediatric cancers is limited, and interpretation can be challenging, especially in cases where results are contrasting to those in adult entities. This review describes recent advances in the molecular characterization of structure and function of telomeres, regulation of telomerase activity in cancer pathogenesis in general, and highlights the key advances that have expanded our views on telomere biology in pediatric cancer, with special emphasis on the central role of telomere maintenance in neuroblastoma. Furthermore, open questions in the field of telomere maintenance research are discussed in the context of recently published literature.

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The prognostic significance of hTERT overexpression in cancers

Abstract: Our comprehensive systematic review concluded that the overexpression of hTERT was associated with poor survival in human solid tumors. hTERT may be a valuable predictive biomarker for prognosis.

Cited by 35 publications

References 45 publications

Telomere length, vitamin B12 and mortality in persons undergoing coronary angiography: the Ludwigshafen risk and cardiovascular health study

Telomere length, vitamin B12 and mortality in persons undergoing coronary angiography: the Ludwigshafen risk and cardiovascular health study

MicroRNA-Based Cancer Mortality Risk Scoring System and hTERT Expression in Early-Stage Oral Squamous Cell Carcinoma

Telomere Maintenance in Pediatric Cancer

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