| 1. |
- Edler, David, et al.
(författare)
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The expression of the novel CYP2W1 enzyme is an independent prognostic factor in colorectal cancer : a pilot study.
- 2009
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 45:4, s. 705-712
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Tidskriftsartikel (refereegranskat)abstract
- AIM Cytochrome P450 (CYP) enzymes are important for drug metabolism. A novel cytochrome P450 enzyme, CYP2W1, has recently been identified. This enzyme is mainly found in foetal colon tissue and in tumour tissue. In this pilot study, we have investigated the expression of CYP2W1 in 162 tumours from patients with stages II and III colorectal cancer. METHODS The expression of CYP2W1 enzyme was immunohistochemically detected using a polyclonal antibody. Staining intensity was defined using a visual grading scale from 0 to 3. Grades 0-2 were classified as low, and grade 3 was classified as high expression of CYP2W1. RESULTS About 64% of the tumours expressed a low level of CYP2W1-expression, and 36% expressed a high level. CYP2W1-expression was an independent prognostic factor for overall survival (p=0.007), where a high expression was associated with a worse clinical outcome. CONCLUSIONS Immunohistochemically assessed expression of CYP2W1 is an independent prognostic factor in patients with stages II and III colorectal cancer.
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| 2. |
- Kersten, Christian, et al.
(författare)
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Increased C-reactive protein implies a poorer stage-specific prognosis in colon cancer
- 2013
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Ingår i: Acta Oncologica. - : Informa Plc. - 0284-186X .- 1651-226X. ; 52:8, s. 1691-1698
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To characterize the stage-specific prognostic relevance of preoperative systemic inflammatory response, defined by C-reactive protein (CRP), in colon cancer (CC) patients.MATERIAL AND METHODS: Data from CC patients operated on from 1998 to 2007 at three hospitals from three different Nordic countries were collected retrospectively from national registries, local databases and/or patient records. Patients with emergency surgery, infection or auto-immune disease were excluded. Associations between clinical or histopathological variables and CRP were assessed. Patients were followed from the date of surgery to death or end of follow-up. Disease-specific survival (DSS) was the main endpoint.RESULTS: In total, 525 patients with age and stage distributions which were representative for CC patients were included. None of the patients was lost to follow-up. Age, TNM Stage, WHO differentiation grade and right-sided tumor location significantly associated with elevated CRP values, in contrast to postoperative morbidity, which did not. CRP levels were found to be a strong prognostic factor for DSS in CC. The risk of death due to CC was augmented with increasing levels of CRP in every stage of operated CC. Both short- and long-term DSS were impaired. The sub-hazard ratios for CRP-levels above 60 mg/L were 7.37 (CI 2.65-20.5) for stage I+ II, compared to 3.29 (CI 1.30-8.29) for stage III and 2.24 (CI 1.16-4.35) for stage IV.CONCLUSION: Increase of CRP concentrations correlate with clinically relevant poorer disease-specific survival in each stage of CC.
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| 3. |
- Stenstedt, Kristina
(författare)
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CYP2W1 in colorectal cancer : aspects of risk, prognosis and future treatment options
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Colorectal cancer (CRC) is a common disease and a major cause of cancer related death globally. Prognosis is rather good in early stages but worse in cases with disseminated disease. There is a constant need of developing all treatment modalities, which also has been done over the last decades. There are needs to find predictive markers in order to assess who will and who will not benefit of chemotherapy, just as there are needs to develop drugs targeting novel pathways and proteins prevalent in primary tumors and metastases. CYP2W1 is a member of the cytochrome P450 superfamily of enzymes with unknown physiological functions but found to have the capacity to metabolize both carcinogens and various other xenobiotic substances. It is expressed in fetal rat colonic tissue and in human colorectal tumors, but not to our knowledge in any adult normal human tissue. CYP2W1 expression, both mRNA and protein, has previously been studied in a material consisting of about 50 colorectal tumor samples. We wanted to investigate the extent of CYP2W1 expression in a larger tumor material using immunohistochemistry. We found it also interesting to see if CYP2W1 expression affects prognosis. Another aim of the thesis was to assess the association between polymorphism in the CYP2W1 gene and risk to develop CRC. A last aim was to evaluate the CYP2W1 expression in metastases. For the first aim, we used three different patient cohorts, two of which were derived from a randomized Nordic trial aiming to compare no adjuvant versus adjuvant treatment in patients with stage II and III CRC. These cohorts consisted of 162 and 235 patients respectively. The third patient cohort consisted of 96 patients being resected for liver metastases from CRC. All tumor manifestations in these patients were investigated with immunohistochemistry, addressing both the first and the last aim, and the findings indicate that CYP2W1 is expressed at high levels in between 26-36% of the primary tumors. It is expressed in about one third of lymph node metastases and almost half of the liver metastases. We performed two investigations regarding CYP2W1 as a prognostic factor using the two cohorts from the Nordic study (n=162 and n=235). In the first study, high CYP2W1 expression was of independent prognostic value for poor survival together with stage. In the second study aiming to reproduce this, the result was not as clear-cut, CYP2W1 was of prognostic value only in multivariate analysis but not in univariate analysis. In the subgroup of patients with stage III CRC (n=132), CYP2W1 expression was of independent prognostic value. The third aim was addressed using a material of DNA from individuals in a large case-control study aiming to investigate various polymorphisms and their relation to CRC risk. DNA from 1785 CRC patients and 1761 control subject was analyzed regarding three CYP2W1 variants. We also experimentally assessed enzymatic activity of the gene products of the variants studied. No difference was seen, neither in CRC risk between cases and controls, nor in enzymatic activity between the three variant proteins. In conclusion, CYP2W1 seems to be expressed in about one third of primary CRC and half of the liver metastases. The association with prognosis in CRC requires further studies to be elucidated. Genetic polymorphism in the CYP2W1 gene does not seem to have any impact on CRC risk. The tumor specific expression of a catalytic enzyme in CRC and metastases is interesting in the aspect of future targeted anti-cancer therapies.
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