Relationship between tumor and plasma levels of hTERT mRNA in patients with colorectal cancer: implications for monitoring of neoplastic disease.
OBJECTIVE
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.


METHODS
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-AT was 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.
Terrin
Liliana
L
Department of Oncology and Surgical Sciences, Section of Oncology, University of Padova, Padova, Italy.
Rampazzo
Enrica
E
Pucciarelli
Salvatore
S
Agostini
Marco
M
Bertorelle
Roberta
R
Esposito
Giovanni
G
DelBianco
Paola
P
Nitti
Donato
D
De Rossi
Anita
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis*; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D019098:Telomerase / Q000032:analysis* / Q000096:biosynthesis* / Q000235:genetics
D015415:Biomarkers; D012333:RNA, Messenger; C509186:TERT protein, human; D019098:Telomerase