Relationship of telomere length in colorectal cancer patients with cancer phenotype and patient prognosis

Abstract

BACKGROUND: Telomeres, repetitive DNA capping ends of eukaryotic chromosomes, are important in the maintenance of genomic integrity. Perturbed telomeres are common features of many human malignancies, including colorectal cancer. METHODS: Telomere length (TL), measured by a Monochrome Multiplex Real-Time qPCR, was investigated in tumour tissues, adjacent mucosa, and blood from patients with colorectal cancer with different clinicopathological features and its impact on patient survival. TL was also measured in a limited number of liver metastases, non-cancerous liver tissues or corresponding tissues from the same patients. RESULTS: TL in tumour tissues was shorter than in the adjacent mucosa (P < 0.0001). Shorter TL was observed in tumours with lower stage than in those with advanced stages (P = 0.001). TL was shorter in tumours at the proximal than at the distal sites of the colon (P < 0.0001). Shorter TL was also associated with microsatellite instability (P = 0.001) and mucinous tumour histology (P < 0.0001). Patients with a smaller TL ratio between tumour tissues and the adjacent mucosa were associated with increased overall survival (P = 0.022). Metastasised tumours had shorter telomeres than the adjacent non-cancerous liver tissues (P = 0.0005). CONCLUSIONS: Overall, the results demonstrate differences in TL between tumours and the adjacent mucosa, between tumours located at different sites and association with patient survival.

TRF2 and VEGF-A: an unknown relationship with prognostic impact on survival of colorectal cancer patients

“…In the last few times there has been a rapid growth in the number of clinical studies aimed at identifying biomarkers able to discriminate the patients that might take a real advantage from administration of therapies beyond the surgical treatment. In this scenario, telomeres were evaluated as a putative prognostic factor in CRC, even if lack of solid evidences and a limited amount of available data raise many doubts about their effective clinical relevance [15,16,21]. Conversely, the telomeric proteins have been poorly investigated in clinical studies and very little is still known about their role as tumor biomarkers [43,44].…”

“…Recently, telomere length has been accounted as a putative prognostic marker for solid tumors, included CRC [15,16]. Telomeres are specialized nucleoprotein structures, located at the terminal portion of chromosomes, playing a central role in the maintenance of genomic integrity [17].…”

Selective Elimination of Osteosarcoma Cell Lines with Short Telomeres by ATR Inhibitors

“…To independently confirm the telomere length predictions based on TRF assessment, we used MM-qPCR, which determines telomeric repeat number relative to the repeat number of a reference gene [40]. In addition, MM-qPCR is suitable to determine telomere status in patient derived tumour samples [14,41,42]. To reduce errors caused by potential aneuploidy that may variably exist in the cancer lines, we used two different single copy number genes (SCGs) present on different chromosomes, ALB encoding albumin (4q13.3) and HBB encoding beta-globin (11q15.4).…”

“…Interestingly, the activity or expression levels of telomerase in cancers does not seem to correlate with the length of telomeres that are maintained [6,9,10]. A substantive fraction of telomerase-positive cancers display abnormally short telomeres compared to adjacent noncancerous tissue [6,[11][12][13][14][15]. Furthermore, shortness of telomeres in tumours is correlated with poor prognosis in many types of cancer [14][15][16].…”

“…A substantive fraction of telomerase-positive cancers display abnormally short telomeres compared to adjacent noncancerous tissue [6,[11][12][13][14][15]. Furthermore, shortness of telomeres in tumours is correlated with poor prognosis in many types of cancer [14][15][16]. Whereas the origin of short telomeres in tumours has not been clearly demonstrated, shortness or loss of telomeres is thought to originate from excessive divisions at the benign stages [1,2,17].…”