Relationship Between Tumor and Plasma Levels of hTERT mRNA in Patients with Colorectal Cancer: Implications for Monitoring of Neoplastic Disease

Abstract

Purpose: Colorectal cancer (CRC) is one of the most common cancers in western countries.Identification of circulating markers for CRC would optimize early stage diagnosis and the monitoring for disease recurrence. Expression of telomerase reverse transcriptase (hTERT) is essential to the oncogenic process and might be used as a molecular marker of neoplastic disease. Experimental Design: Eighty-five CRC samples (25 stage I, 15 stage II, 15 stage III, and 30 stage IV), the available corresponding noncancerous mucosa (n = 42), and plasma collected at the time of surgery (n = 49) were analyzed. Control plasma samples were obtained from 43 age-matched healthy subjects. All hTERT transcripts (hTERT-AT) and transcripts encoding the functional protein (hTERT-FL) were quantified by real-time PCR.Results: hTERT-ATwas found to correlate with hTERT-FL (r = 0.849; P < 0.0001) mRNA levels in tumors. Both hTERT mRNAs were significantly higher in tumors than in adjacent noncancerous mucosa and both significantly increased with tumor progression (P < 0.0001). In contrast to controls, all but two plasma samples from CRC patients were positive for hTERT mRNAs. Using the cutoff value of 180 copies hTERT-AT/mL, the sensitivity and specificity of the assay for CRC detection were 92% and 100%, respectively. Furthermore, hTERT-AT mRNA levels in plasma significantly correlated with hTERT-AT mRNA levels in tumors (r = 0.702, P < 0.0001).Conclusions: These findings indicate that quantification of hTERT mRNA in plasma may be used as a marker for detection and monitoring of neoplastic colorectal disease.

Relationship between telomere shortening, genetic instability, and site of tumour origin in colorectal cancers

“…We did not find any relationship between telomere length and tumour progression. In agreement with previous studies (Terrin et al, 2008), levels of hTERT increased with tumour progression; it is conceivable that telomere length may stabilise with tumour progression because of an increase in telomerase activity compensating for replicative telomere loss. It should be pointed out that B15% of CRCs presented MSI-H, whereas the p53 gene is the known major genetic alteration in CRCs with MSS (Kim et al, 2007;Ogino et al, 2009).…”

“…The quantification of all hTERT transcripts (hTERT-AT) in CRC samples was carried out by real-time PCR, exactly as previously described (Terrin et al, 2007(Terrin et al, , 2008, and normalised for 10 3 copies of the housekeeping hypoxanthine guanine phosphoribosyl transferase 1 (HPRT1) gene (Terrin et al, 2008).…”

Relevance of circulating tumor cells, extracellular nucleic acids, and exosomes in breast cancer

“…Similarly the presence of exRNA is well documented in sera/plasma from patients presenting with breast [62][63][64] and colon cancers [65,66].…”

“…Detection of hTERT expression either in plasma [65,112], peripheral blood mononuclear cells [113] or by IHC in primary tumors [114] has been identified as diagnostic for prostate, colon, esophageal cancers, and paragangliomas, respectively. In terms of breast cancer, Chen et al [97] identified hTERC and hTERT mRNA in primary tumors and sera of breast cancer patients presenting with invasive lobular carcinoma and invasive ductal carcinoma.…”

RuvBl2 cooperates with Ets2 to transcriptionally regulate hTERT in colon cancer

“…3B). Though previous studies have reported an association between hTERT expression levels and disease progression in colorectal cancer [47][48][49], these studies primarily looked at hTERT transcript levels. Here, 78% of colon tumours expressed hTERT protein, 8% of which had nuclear hTERT expression, similar levels of hTERT expression in colorectal tumours have been previously reported [50].…”