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The prognostic significance of tryptophanyl-tRNA synthetase in colorectal cancer
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
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2009 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 18, no 11, 2949-2956 p.Article in journal (Refereed) Published
Abstract [en]

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). CONCLUSION: 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.

Place, publisher, year, edition, pages
2009. Vol. 18, no 11, 2949-2956 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-113326DOI: 10.1158/1055-9965.EPI-09-0456ISI: 000271562600022PubMedID: 19900940OAI: oai:DiVA.org:uu-113326DiVA: diva2:290461
Available from: 2010-01-27 Created: 2010-01-27 Last updated: 2014-07-25Bibliographically approved
In thesis
1. Colorectal Cancer: Aspects of Heredity, Prognosis and Tumour Markers
Open this publication in new window or tab >>Colorectal Cancer: Aspects of Heredity, Prognosis and Tumour Markers
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Colorectal cancer (CRC) is one of the most common cancer types and leading causes of cancer death worldwide. Since CRC is a heterogenic disease, there is a demand for increased knowledge of the underlying genetic and epigenetic mechanisms. The aim of this thesis was to investigate heredity and potential tumour markers in relation to prognosis. In paper I, survival of patients with CRC and a positive family history of CRC in first-degree relatives was analysed. Patients with colon cancer and positive family history of CRC had improved survival compared to patients with negative family history. This improvement in survival could not be explained by known clinico-pathological factors. In paper II, we investigated the prognostic value of Tryptophanyl t-RNA synthetase (TrpRS) in tissues from patients operated for CRC. Low protein expression of TrpRS in primary tumour tissues correlated with increased risk of recurrence and poorer survival. In paper III, the prognostic value of microsatellite instability (MSI) and the correlation to heredity for CRC in first-degree relatives was investigated. Patients with proximal colon cancer and MSI had improved cancer specific survival. There were no correlation between MSI and heredity. In paper IV, we evaluated the potential use of proximity ligation assay (SP-PLA) in patients with CRC, by simultaneous analysis of 35 proteins in only 5 μl plasma. SP-PLA is a suitable method for protein detection and might give valuable guidance in pursuing new prognostic and predictive tumour markers. However, none of the markers selected for present SP-PLA analyses gave better prognostic information than CEA. In conclusion, heredity is related to better survival independent of MSI in patients with CRC and MSI is associated with better prognosis in proximal colon cancer. Detection and increased knowledge of molecular mechanism in CRC is important, however it needs to be further investigated and validated in clinical use. 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. 68 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1011
colorectal cancer, heredity, Tryptophanyl t-RNA synthetase, microsatellite instability, SP-PLA, prognosis, biomarkers
National Category
Medical and Health Sciences
urn:nbn:se:uu:diva-224624 (URN)978-91-554-8975-5 (ISBN)
Public defence
2014-09-06, Grönwallsalen, Akademiska sjukhuset, ingång 70, bv, Uppsala, 09:15 (Swedish)
Available from: 2014-06-13 Created: 2014-05-15 Last updated: 2014-07-25

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Pontén, Fredrik
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