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Growth differentiation factor 15: a prognostic marker for recurrence 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 Radiology, Oncology and Radiation Science, Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
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2011 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 104, no 10, 1619-1627 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Growth differentiation factor 15 (GDF15) belongs to the transforming growth factor beta superfamily and has been associated with activation of the p53 pathway in human cancer. The aim of this study was to assess the prognostic value of GDF15 in patients with colorectal cancer (CRC). METHODS: Immunohistochemistry and tissue microarrays were used to analyse GDF15 protein expression in 320 patients with CRC. In a subgroup of 60 patients, the level of GDF15 protein in plasma was also measured using a solid-phase proximity ligation assay. RESULTS: Patients with CRC with moderate to high intensity of GDF15 immunostaining had a higher recurrence rate compared with patients with no or low intensity in all stages (stages I-III) (HR, 3.9; 95% CI, 1.16-13.15) and in stage III (HR, 10.32; 95% CI, 1.15-92.51). Patients with high plasma levels of GDF15 had statistically shorter time to recurrence (P = 0.041) and reduced overall survival (P = 0.002). CONCLUSION: Growth differentiation factor 15 serves as a negative prognostic marker in CRC. High expression of GDF15 in tumour tissue and high plasma levels correlate with an increased risk of recurrence and reduced overall survival.

Place, publisher, year, edition, pages
2011. Vol. 104, no 10, 1619-1627 p.
Keyword [en]
GDF15, colorectal cancer, prognostic markers, MIC-1
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-154348DOI: 10.1038/bjc.2011.112ISI: 000290471600014PubMedID: 21468045OAI: oai:DiVA.org:uu-154348DiVA: diva2:420099
Available from: 2011-05-31 Created: 2011-05-31 Last updated: 2012-01-05Bibliographically approved
In thesis
1. Cancer of the Colon and Rectum: Prognostic Factors and Early Detection
Open this publication in new window or tab >>Cancer of the Colon and Rectum: Prognostic Factors and Early Detection
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Colorectal cancer (CRC) is one of the most common causes of death from malignant disease. Nevertheless, no ideal screening method exists and there is a lack of prognostic and predictive factors to support clinical decisions and to aid the development of a more individualized treatment for patients with CRC. The aim of this thesis was to investigate early detection, prognostic and predictive factors of CRC. In the first paper, a novel method to collect cells for DNA quantification from the rectal mucosa was investigated. The sensitivity and specificity of this test to detect CRC or any pathology in colon and rectum were ultimately too low to be acceptable. In the second paper, the prognostic value of growth differentiation factor 15 (GDF 15) was evaluated in patients curatively operated for colorectal cancer. GDF 15 expression was demonstrated to be associated with a negative prognosis in patients with stages I-III and III disease. In the third paper, the prognostic value of BRAF, PIK3CA KRAS and MSI was evaluated in a cohort of patients with CRC stratified by disease and recurrence. The results indicated that patients with CRC stage III without recurrence have a higher frequency of BRAF mutation compared to stage III patients with recurrence. In the fourth paper, histopathological predictors of pathologic complete response (pCR) as well as the association between pre-treatment carcinoembryonic antigen (CEA) levels and pCR in non-smoking and smoking patients receiving preoperative chemo-radiotherapy for rectal cancer were evaluated. Only in non-smokers was a low CEA level significantly associated with pCR, suggesting that the predictive value of CEA for pCR in rectal cancer in smokers can be limited. In sum, this research has investigated a new method for CRC detection and further evaluated the clinical use of prognostic and predictive markers in CRC.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 83 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 706
colorectal cancer screening predictive markers prognostic markers
National Category
urn:nbn:se:uu:diva-159142 (URN)978-91-554-8166-7 (ISBN)
Public defence
2011-11-04, Hedstrand salen, Akademiska sjuhuset, ing. 70 bv, Uppsala, 13:00 (Swedish)
Available from: 2011-10-14 Created: 2011-09-22 Last updated: 2012-06-14Bibliographically approved

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Wallin, UlrikPåhlman, LarsBirgisson, Helgi
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Colorectal SurgeryOncologyDepartment of Immunology, Genetics and PathologyMolecular and Morphological Pathology
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