Correlations of telomere length, telomerase activity, and telomeric-repeat binding factor 1 expression in colorectal carcinoma.
BACKGROUND
Telomere maintenance has been proposed as an essential step for tumor cell immortalization. The objectives of the current study were to investigate the mechanisms implicated in telomere length in colorectal carcinoma (CRC) and to evaluate the prognostic impact of telomere status.


METHODS
Ninety-one colorectal carcinoma samples that were obtained from patients who underwent surgery were analyzed to investigate the factors related to telomere function. The authors studied telomerase activity, terminal restriction fragment (TRF) length, and telomeric-repeat binding factor (TRF1) expression and analyzed the prognostic implications of those factors.


RESULTS
Most tumors (81.3%) displayed telomerase activity. Overall, telomeres in CRC specimens were significantly shorter compared with telomeres in normal, adjacent specimens (P=0.02). Moreover, tumors that demonstrated shortened telomeres displayed higher TRF1 levels than tumors without telomere shortening. In relation to patient prognosis, a significantly poor clinical course was observed in the group of patients who had tumors with longer telomeres (P=0.02), and this finding emerged as an independent prognostic factor in a Cox proportional hazards model (P=0.04; relative risk, 6.48). Among patients with tumors classified as telomerase-positive, telomere length ratios (the ratio of tumor tissues to normal tissues)<or=0.66 or TRF1 over-expression conferred a favorable outcome (P=0.03 and P=0.05, respectively).


CONCLUSIONS
The majority of CRC specimens in the current study displayed telomerase reactivation. However, only those tumors that displayed telomere elongation conferred a poor prognosis. Conversely, colorectal tumors that over-expressed TRF1 demonstrated telomere shortening, and patients with those tumors had a better clinical course.
Garcia-Aranda
Cristina
C
Departamento de Bioquimica y Biologia Molecular, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
de Juan
Carmen
C
Diaz-Lopez
Antonio
A
Sanchez-Pernaute
Andres
A
Torres
Antonio-Jose
AJ
Diaz-Rubio
Eduardo
E
Balibrea
Jose-Luis
JL
Benito
Manuel
M
Iniesta
Pilar
P
D000368:Aged; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000648:ultrastructure*; D035321:Telomeric Repeat Binding Protein 1 / Q000096:biosynthesis*
D035321:Telomeric Repeat Binding Protein 1; D019098:Telomerase