The prognostic significance of tryptophanyl-tRNA synthetase in colorectal cancer.
BACKGROUND
Tryptophanyl-tRNA synthetase (TrpRS) is an aminoacyl-tRNA synthetase involved in protein synthesis and regulation of RNA transcription and translation and is an inhibitor of angiogenesis. TrpRS has been shown to be differentially expressed in colorectal cancer (CRC) and has thus been identified as a potential prognostic marker. The aim of this study was to analyze the correlation of TrpRS to the prognosis of patients diagnosed and treated for CRC within a defined population.


METHODS
With a polyclonal, monospecific IgG antibody, TrpRS expression was assessed by immunohistochemistry on tissue microarrays with tumors from a population-based CRC cohort (n = 320). Staining intensity and fraction of positive tumor cells were recorded. A Cox multivariate model including TrpRS expression, carcinoembryonic antigen, age, stage, tumor differentiation, and lymphatic and vascular vessel invasion was used to calculate the hazard ratio and 95% confidence interval (95% CI) for time to recurrence, disease-free survival, and overall survival.


RESULTS
Low expression of TrpRS correlated to increased risk for lymph node metastasis (P = 0.025) and a more advanced tumor stage (P = 0.001). Patients with tumors and increased levels of TrpRS expression had better survival than patients with low expression levels. Multivariate analyses revealed significantly better disease-free survival (relative risk, 0.59; 95% CI, 0.38-0.95) for patients with high expression than for patients with low expression of TrpRS. For colon cancer patients, a reduced risk for recurrence was seen in patients with increased TrpRS expression (relative risk, 0.23; 95% CI, 0.07-0.80).


CONCLUSIONS
Low expression of TrpRS in tumor tissue correlates with increased risk for recurrence and worse survival in patients with CRC. This can be related to its antiangiogenic properties and could aid in the future selection of new drugs in the treatment of CRC.
Ghanipour
Arezo
A
Department of Surgery, University of Uppsala, Uppsala, Sweden. arezo_g@hotmail.com
Jirström
Karin
K
Pontén
Fredrik
F
Glimelius
Bengt
B
Påhlman
Lars
L
Birgisson
Helgi
H
D002272:Carcinoembryonic Antigen / Q000378:metabolism; D002454:Cell Differentiation; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000201:enzymology* / Q000473:pathology; D008207:Lymphatic Metastasis; D009092:Mucous Membrane; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000201:enzymology* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D046888:Tissue Array Analysis; D014369:Tryptophan-tRNA Ligase / Q000378:metabolism*
D002272:Carcinoembryonic Antigen; D014369:Tryptophan-tRNA Ligase