Differential Expression of Senescence and Cell Death Factors in Non-Small Cell Lung and Colorectal Tumors Showing Telomere Attrition

Fernández-Marcelo, Tamara; Morán, Alberto; Juan, Carmen; Pascua, Irene; Head, Jacqueline; Gómez, Ana María; Trancho, Florentino Hernando; López-Asenjo, José A.; Hernández, Susana; Sánchez‐Pernaute, Andrés; Torres, Antonio; Benito, Manuel; Iniesta, Pilar

doi:10.1159/000335678

Cited by 6 publications

(7 citation statements)

References 75 publications

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“…A possible molecular explanation for this fact could be the differential regulation of telomerase expression in colorectal epithelial cells [ 39 ]. Also, it may be possible that the viability of senescence and cell death pathways, in response to short telomeres, contributes to limiting tumorigenesis, as we previously hypothesized [ 40 ]. Our results seem to indicate that the telomere attrition could be acting as a tumour suppressor mechanism in CRC.…”

Section: Discussionmentioning

confidence: 99%

Clinical Relevance of Telomere Status and Telomerase Activity in Colorectal Cancer

et al. 2016

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The role of telomeres and telomerase in colorectal cancer (CRC) is well established as the major driving force in generating chromosomal instability. However, their potential as prognostic markers remains unclear. We investigated the outcome implications of telomeres and telomerase in this tumour type. We considered telomere length (TL), ratio of telomere length in cancer to non-cancer tissue (T/N ratio), telomerase activity and TERT levels; their relation with clinical variables and their role as prognostic markers. We analyzed 132 CRCs and paired non-cancer tissues. Kaplan-Meier curves for disease-free survival were calculated for TL, T/N ratio, telomerase activity and TERT levels. Overall, tumours had shorter telomeres than non-tumour tissues (P < 0.001) and more than 80% of CRCs displayed telomerase activity. Telomere lengths of non-tumour tissues and CRCs were positively correlated (P < 0.001). Considering telomere status and clinical variables, the lowest degree of telomere shortening was shown by tumours located in the rectum (P = 0.021). Regarding prognosis studies, patients with tumours showing a mean TL < 6.35 Kb experienced a significantly better clinical evolution (P < 0.001) and none of them with the highest degree of tumour telomere shortening relapsed during the follow-up period (P = 0.043). The mean TL in CRCs emerged as an independent prognostic factor in the Cox analysis (P = 0.017). Telomerase-positive activity was identified as a marker that confers a trend toward a poor prognosis. In CRC, our results support the use of telomere status as an independent prognostic factor. Telomere status may contribute to explaining the different molecular identities of this tumour type.

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Section: Discussionmentioning

confidence: 99%

Clinical Relevance of Telomere Status and Telomerase Activity in Colorectal Cancer

et al. 2016

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“…Therefore, cancer prognosis associated to telomere status could be dependent on the tumour type [ 14 ]. A deficiency in the function of senescence and cell death pathways [ 29 ], or other molecules related to telomere maintenance and genome instability [ 30 ] could explain the unfavorable prognosis for post-surgical patients with NSCLCs and short telomeres. Genetic context underlying telomere status, which confers the different clinical outcome, must be carefully considered.…”

Section: Discussionmentioning

confidence: 99%

Telomere length and telomerase activity in non-small cell lung cancer prognosis: clinical usefulness of a specific telomere status

Fernández-Marcelo

Gómez

Pascua

et al. 2015

J Exp Clin Cancer Res

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BackgroundConsidering previous data and the need to incorporate new biomarkers for the prognosis of solid tumours into the clinic, our aim in this work consists of evaluating the potential clinical use of telomeres and telomerase in non-small cell lung cancer (NSCLC).MethodsTelomere status was established by determination of telomere length using the Terminal Restriction Fragment length method, and telomerase activity by the Telomeric Repeat Amplification Protocol in 142 NSCLCs and their corresponding control samples, obtained from patients submitted to surgery. Group-oriented curves for disease-free survival were calculated according to the Kaplan-Meier method considering telomere length, T/N ratio (telomere length in tumour to control tissue) and telomerase activity.ResultsOverall, tumours had significantly shorter telomeres compared with telomeres in control tissues (P = 0.027). More than 80 % of NSCLCs displayed telomerase activity. Regarding prognosis studies, patients whose tumours showed a mean telomere length (MTL) <7.29 Kb or T/N ratio <0.97 showed a significantly poor clinical evolution (P = 0.034 and P = 0.040, respectively). As result of a Cox multivariate analysis including pathologic state and lymph node dissemination, the MTL and T/N ratio emerged as independent significant prognostic factors.ConclusionsTelomerase activity was identified as a marker of poor prognosis. The novel finding of this study is the independent prognosis role of a specific telomere status in NSCLC patients. According to our results, telomere function may emerge as a useful molecular tool that allow to select groups of NSCLC patients with different clinical evolution, in order to establish personalized therapy protocols.

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“… 17 Depending on the cancer type, both short and long telomeres have been described as markers of risk. 36 In some cases, telomerase expression is considered as a marker of aggressiveness and poor prognosis. 37 Therapies inhibiting the action of telomerase have been shown to be effective in limiting cell growth in some cancers.…”

Section: Telomere Length Dynamics In Aging and Diseasementioning

confidence: 99%

Integration of Telomere Length Dynamics into Systems Biology Framework: A Review

Nersisyan

2016

Gene�Regul Syst Bio

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Telomere length dynamics plays a crucial role in regulation of cellular processes and cell fate. In contrast to epidemiological studies revealing the association of telomere length with age, age-related diseases, and cancers, the role of telomeres in regulation of transcriptome and epigenome and the role of genomic variations in telomere lengthening are not extensively analyzed. This is explained by the fact that experimental assays for telomere length measurement are resource consuming, and there are very few studies where high-throughput genomics, transcriptomics, and/or epigenomics experiments have been coupled with telomere length measurements. Recent development of computational approaches for assessment of telomere length from whole genome sequencing data pave a new perspective on integration of telomeres into high-throughput systems biology analysis framework. Herein, we review existing methodologies for telomere length measurement and compare them to computational approaches, as well as discuss their applications in large-scale studies on telomere length dynamics.

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Differential Expression of Senescence and Cell Death Factors in Non-Small Cell Lung and Colorectal Tumors Showing Telomere Attrition

Cited by 6 publications

References 75 publications

Clinical Relevance of Telomere Status and Telomerase Activity in Colorectal Cancer

Clinical Relevance of Telomere Status and Telomerase Activity in Colorectal Cancer

Telomere length and telomerase activity in non-small cell lung cancer prognosis: clinical usefulness of a specific telomere status

Integration of Telomere Length Dynamics into Systems Biology Framework: A Review

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