Telomere function in colorectal cancer

Frías, Cristina; Morán, Alberto; Juan, Carmen; Ortega, Paloma; Fernández-Marcelo, Tamara; Sánchez‐Pernaute, Andrés; Torres, Antonio; Dı́az-Rubio, Eduardo; Benito, Manuel; Iniesta, Pilar

doi:10.4251/wjgo.v1.i1.3

Cited by 6 publications

(5 citation statements)

References 72 publications

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“…However, several studies, including ours, did not find a significant relationship between telomere length and telomerase levels and/or activity (Frías and Morán 2009; Rampazzo et al , 2010). Several studies suggested that hTERT might increase the malignant potential of tumours beyond just preservation of telomere length.…”

Section: Discussioncontrasting

confidence: 59%

Telomerase is an independent prognostic marker of overall survival in patients with colorectal cancer

et al. 2013

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Background:Colorectal cancer (CRC) is an important cause of cancer-related death. Prediction of recurrence is an important issue in the treatment of disease, particularly for stage II patients. The level of telomere-specific reverse transcriptase (hTERT), the catalytic component of the telomerase complex, increases along with CRC progression, but its prognostic value is still unclear.Methods:One hundred and thirty-seven CRC patients were studied for hTERT expression in tumour cells by real-time PCR. hTERT level was evaluated as a prognostic factor of overall survival (OS) in all patients and of disease recurrence in a subgroup of 50 stage II patients.Results:The median hTERT level was 93.8 copies (interquartile range 48–254). Patients with high hTERT levels (above the median) showed a significantly worse survival than those with low hTERT levels (below the median; log-rank test P<0.0001; hazard ratio (HR)=3.30 (95% confidence interval (CI) 1.98–5.52); P<0.0001). The negative prognostic value of high hTERT level is independent of the pathological stage and microsatellite instability (HR=2.09 (95% CI 1.20–3.64), P=0.009). Moreover, in stage II CRC, high hTERT levels identified patients with a higher risk of disease recurrence (HR=3.06 (95% CI 1.03–9.04), P=0.043) and death (HR=3.24 (95% CI 1.37–7.71), P=0.008).Conclusion:hTERT level is an independent prognostic marker of OS in CRC patients. In addition, assessment of hTERT level could improve stratification of stage II CRC patients for the risk of disease recurrence.

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Section: Discussioncontrasting

confidence: 59%

Telomerase is an independent prognostic marker of overall survival in patients with colorectal cancer

et al. 2013

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“…A multivariate analysis by Sanz-Casla et al examined the impact of telomerase activity in prognosis in 103 CRC patients undergoing surgery, which showed that by adjusting for tumor stage, telomerase activity could be utilized to predict the risk of death or recurrence of CRC [154]. Thus, quantification of telomerase activity may be a useful method of evaluating prognosis in patients with CRC [155]. …”

Section: The Gi Tract Cancers Telomeres and Telomere Maintenance Mementioning

confidence: 99%

Telomeres and telomere dynamics: relevance to cancers of the GI tract

Basu¹,

Skinner²,

Litzelman³

et al. 2013

Expert Review of Gastroenterology & Hepatology

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Summary Aberrations in telomere length and telomere maintenance contribute to cancer development. In this article, we review basic principles of telomere length in normal and tumor tissue and the presence of the two main telomere maintenance pathways as they pertain to GI tract cancer. Peripheral blood telomeres are shorter in patients with many types of GI tract cancers. Telomere length in tumor DNA also appears to shorten early in cancer development. Tumor telomere shortening is often accompanied by telomerase activation to protect genetically damaged DNA from normal cell senescence or apoptosis, allowing immortalized but damaged DNA to persist. Alternative lengthening of telomeres (ALT) is another mechanism used by cancer to maintain telomere length in cancer cells. Telomerase and ALT activators and inhibitors may become important chemopreventive or chemotherapeutic agents as our understanding of telomere biology, specific telomere related phenotypes, and its relationship to carcinogenesis increases.

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“…Wang et al (7) observed that the expression of E-cadherin, β-catenin, glycogen synthase kinase-3β (GSK-3β), cyclin D1 and c-myc was positive in LSTs. Human telomerase reverse transcriptase (hTERT/Hest2/TP2), the main subunit involved in telomerase reverse transcription, is considered as one of the most important proteins affecting telomerase activity (8,9). However, hTERT expression in LSTs has not been thoroughly studied.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of hTERT in potentially malignant colorectal laterally spreading tumors

Cao²,

Fang³

et al. 2013

Molecular Medicine Reports

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Abstract. Human telomerase reverse transcriptase (hTERT) is the main subunit of the core enzyme telomerase, which consists of three subunits. Telomeres are essential for chromosomal stability and integrity, protecting the ends of chromosomes from degradation and preventing chromosomal end fusions and recombination. A loss of telomere function is a major mechanism for the generation of chromosomal abnormalities. Telomere shortening leads to mutations, chromosome rearrangements and translocations. Colorectal laterally spreading tumors (LSTs) are a special type of superficial colorectal tumor. They are considered to have a high malignancy potential. The aim of the present study was to characterize the expression of hTERT in an LST cell line and paraffin sections. Immunohistochemistry was utilized to examine the protein expression of hTERT in the LST cell line, 48 resected LSTs, 48 protruded-type colorectal adenomas (PAs) and 48 normal mucosa samples. Statistical analyses were applied to test the associations between hTERT expression and clinicopathological parameters. The present study demonstrated that the positive expression levels of hTERT in LSTs, PAs and normal mucosa were 60.4, 22.9 and 10%, respectively. Compared with polypi and normal mucosa, the expression levels of hTERT were significantly increased in LSTs. The expression of hTERT was also observed in the LST cell line. The expression of hTERT was significantly higher in LSTs, which may indicate a potential for malignancy. IntroductionColorectal laterally spreading tumors (LSTs) of the colon and rectum are defined as lesions >10 mm in diameter with a low vertical axis that extend laterally along the luminal wall (1). The clinical characteristics of LSTs include a flat and superficial growth pattern. Although LSTs are known as adenomas or 'pre-existing cancers', they have been hypothesized to have malignant potential. LSTs are divided into two macroscopic subtypes, flat (F)-type and protruded-type (2). Despite the distinctive biological behaviors of LSTs, a number of genetic alterations have been reported, including K-ras and p53 mutations and cyclooxygenase 2 overexpression (3-6). Wang et al (7) observed that the expression of E-cadherin, β-catenin, glycogen synthase kinase-3β (GSK-3β), cyclin D1 and c-myc was positive in LSTs. Human telomerase reverse transcriptase (hTERT/Hest2/TP2), the main subunit involved in telomerase reverse transcription, is considered as one of the most important proteins affecting telomerase activity (8,9). However, hTERT expression in LSTs has not been thoroughly studied. Thus, this study aimed to elucidate the expression levels of hTERT in LSTs, colorectal tumors with a high malignancy potential. Materials and methodsLST cell line. The novel LST cell line was obtained from the Department of Gastroenterology, Nan Fang Hospital, Affiliated Hospital of Nan Fang Medical University, China. The LST cell line was established from a human rectal villous adenoma obtained using endoscopic resection. A magnifying endoscope showed a flat...

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Telomere function in colorectal cancer

Cited by 6 publications

References 72 publications

Telomerase is an independent prognostic marker of overall survival in patients with colorectal cancer

Telomerase is an independent prognostic marker of overall survival in patients with colorectal cancer

Telomeres and telomere dynamics: relevance to cancers of the GI tract

Overexpression of hTERT in potentially malignant colorectal laterally spreading tumors

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