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  • 1.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Slind Olsen, Renate
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. County Hospital Ryhov, Sweden.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Matussek, Andreas
    County Hospital Ryhov, Sweden.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    PDGF-D gene polymorphism is associated with increased cardiovascular mortality in elderly men2016In: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 17, no 62Article in journal (Refereed)
    Abstract [en]

    Background: Platelet-derived growth factor (PDGF) D has been reported to be active in fibroblasts, and in areas of myocardial infarction. In this longitudinal study we evaluated the association between PDGF-D polymorphism and cardiovascular mortality, and attempted to discover whether specific genotype differences regarding risk could be observed, and if gender differences could be seen. Methods: Four hundred seventy-six elderly community participants were included in this study. All participants underwent a clinical examination, echocardiography, and blood sampling including PDGF-D single nucleotide polymorphism (SNP) analyses of the rs974819 A/A, G/A and G/G SNP. The follow-up time was 6.7 years. Results: No specific genotype of rs974819 demonstrated increased cardiovascular mortality in the total population, however, the male group with genotypes A/A and G/A demonstrated an increased risk that persisted in a multivariate evaluation where adjustments were made for well-known cardiovascular risk factors (2.7 fold compared with the G/G genotype). No corresponding finding was observed in the female group. Conclusion: We report here for the first time that the genotypes G/A or A/A of the SNP rs974819 near PDGF-D exhibited a 2.7 fold increased cardiovascular mortality risk in males. Corresponding increased risk could not be observed in either the total population and thus not in the female group. However, the sample size is was small and the results should be regarded as hypothesis-generating, and thus more research in the field is recommended.

  • 2.
    Dimberg, Jan
    et al.
    Jonköping University, Sweden.
    Skarstedt, Marita
    Regional Jönköping County, Sweden.
    Slind Olsen, Renate
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Regional Jönköping County, Sweden.
    Andersson, Roland E.
    Regional Jönköping County, Sweden.
    Matussek, Andreas
    Regional Jönköping County, Sweden.
    Gene polymorphism in DNA repair genes XRCC1 and XRCC6 and association with colorectal cancer in Swedish patients2016In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 124, no 9, p. 736-740Article in journal (Refereed)
    Abstract [en]

    The DNA repair genes XRCC1 and XRCC6 have been proposed to participate in the pathological process of cancer by modulating the DNA repair capacity. This study evaluated the susceptibility of the single-nucleotide polymorphisms (SNPs) XRCC1 (rs25487, G amp;gt; A) and XRCC6 (rs2267437, C amp;gt; G) to colorectal cancer (CRC) and their association with clinical parameters in Swedish patients with CRC. Using the TaqMan system, these SNPs were screened in 452 patients and 464 controls. No significant difference in genotype distribution was found between the patients and controls, or any significant association with cancer-specific or disease-free survival in patients. However, we showed that the carriers of allele A in XRCC1 (rs25487, G amp;gt; A) were connected with a higher risk of disseminated CRC (Odds Ratio = 1.64; 95% Confidence Interval = 1.12-2.41, p = 0.012).

  • 3.
    Dimberg, Jan
    et al.
    University of Coll Health Science, Sweden .
    Slind Olsen, Renate
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Skarstedt, Marita
    Ryhov County Hospital, Sweden .
    Lofgren, Sture
    Ryhov County Hospital, Sweden .
    Zar, Niklas
    Ryhov County Hospital, Sweden .
    Matussek, Andreas
    Ryhov County Hospital, Sweden .
    Polymorphism of the p38 beta gene in patients with colorectal cancer2014In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 8, no 3, p. 1093-1095Article in journal (Refereed)
    Abstract [en]

    The p38 mitogen-activated protein kinase (MAPK) signaling pathways have been proposed to participate in the pathological process of cancer by affecting inflammation, proliferation, metastasis and cell survival. A single nucleotide polymorphism (SNP; rs2235356, -1628A -greater than G) in the promoter region of the p38 beta gene has been proposed as a genetic modifier for colorectal cancer (CRC) in a Chinese population. The present study evaluated the susceptibility of patients possessing this SNP to CRC, in addition to determining its association with clinical parameters in Swedish patients with CRC. Using the LightSNiP genotyping assay, this SNP was screened in 389 patients with CRC and 517 control subjects. No significant difference in the genotype distribution or in the allelic frequencies was identified between the two groups nor was any association identified with the clinical parameters. These findings indicate that the -1628A -greater than G polymorphism of the p38 beta gene is not significantly associated with a susceptibility to CRC in a Swedish population.

  • 4.
    Duvetorp, Albert
    et al.
    Regional Jönköping County, Sweden.
    Slind Olsen, Renate
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Regional Jonköping County, Sweden.
    Nyström, Helena
    Regional Jonköping County, Sweden.
    Skarstedt, Marita
    Regional Jonköping County, Sweden.
    Dienus, Olaf
    Regional Jonköping County, Sweden.
    Mrowietz, Ulrich
    University of Medical Centre Schleswig Holstein, Germany.
    Soederman, Jan
    Regional Jonköping County, Sweden.
    Seifert, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Regional Jonköping County, Sweden.
    Expression of low-density lipoprotein-related receptors 5 and 6 (LRP5/6) in psoriasis skin2017In: Experimental dermatology, ISSN 0906-6705, E-ISSN 1600-0625, Vol. 26, no 11, p. 1033-1038Article in journal (Refereed)
    Abstract [en]

    Low-density lipoprotein-related receptors 5 and 6 (LRP5/6) are transmembrane receptors with key functions in canonical Wnt signalling. Wnt ligands are thought to play an important role in innate immunity and psoriasis, and recent studies assigned LRP5/6 anti-inflammatory properties. The objective of this study was to investigate the expression of LRP5 and LRP6 in lesional and non-lesional skin in peripheral blood and in mononuclear cells of patients with chronic plaque type psoriasis compared with control individuals. To investigate the effect of UV-B radiation, LRP5/6 skin gene expression was analysed before and after narrowband UV-B treatment. Our results showed significantly decreased gene expression of LRP5 and LRP6 in lesional skin and in peripheral blood from patients with psoriasis compared with non-lesional skin and healthy control skin. Immunohistochemistry did not reveal differences in protein expression of LRP5/6. Narrowband UV-B treatment induced a significant increase in LRP5 and LRP6 gene expression in lesional skin. Decreased gene expression of LRP5/6 in lesional skin and upregulation after nb UV-B treatment suggest a possible role for LRP5/6 in psoriasis.

  • 5.
    Duvetorp, Albert
    et al.
    Regional Jönköping County, Sweden.
    Slind Olsen, Renate
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Regional Jonköping County, Sweden.
    Skarstedt, Marita
    Regional Jonköping County, Sweden.
    Söderman, Jan
    Regional Jonköping County, Sweden.
    Seifert, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Regional Jonköping County, Sweden.
    Psoriasis and Pro-angiogenetic Factor CD93: Gene Expression and Association with Gene Polymorphism Suggests a Role in Disease Pathogenesis2017In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 97, no 8, p. 916-921Article in journal (Refereed)
    Abstract [en]

    CD93 is involved in angiogenesis and inflammation, both of which are key processes in the pathogenesis of psoriasis. CD93 was studied in serum, peripheral blood mononuclear cells and skin of patients with psoriasis and controls. Furthermore, allele frequencies for CD93 single-nucleotide polymorphisms rs2749812 and rs2749817 were assessed in patients with psoriasis compared with controls and the effect of narrow-band ultraviolet B (NB-UVB) treatment on CD93 gene expression was evaluated in the skin of patients with psoriasis. CD93 gene expression was significantly increased in lesional and non-lesional skin from patients with psoriasis compared with controls. Immunohistochemistry revealed CD93 staining in dermal endothelial cells in lesional skin, and psoriasis was significantly associated with rs2749817 CD93 gene polymorphism. NB-UVB treatment of patients with psoriasis did not alter skin CD93 gene expression. Increased protein expression of CD93 psoriatic skin and association with the rs2749817 polymorphism suggests that CD93 plays a role in psoriasis disease pathogenesis.

  • 6.
    Gacic, Jelena
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology.
    Vorkapic, Emina
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Slind Olsen, Renate
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. County Hospital Ryhov, Sweden.
    Söderberg, Daniel
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Gustafsson, Therese
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Geffers, Robert
    Helmholtz Centre Infect Research, Germany.
    Skoglund, Karin
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Matussek, Andreas
    County Hospital Ryhov, Sweden.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Imatinib reduces cholesterol uptake and matrix metalloproteinase activity in human THP-1 macrophages2016In: Pharmacological Reports, ISSN 1734-1140, E-ISSN 2299-5684, Vol. 68, no 1, p. 1-6Article in journal (Refereed)
    Abstract [en]

    Background: Imatinib mesylate (Glivec, formerly STI-571) is a selective tyrosine kinase inhibitor used for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. However, there are reports suggesting that imatinib could be atheroprotective by lowering plasma low-density lipoprotein (LDL). Aim: To investigate the potential inhibitory effect of imatinib on cholesterol uptake in human macrophages as well as its effect on matrix metalloproteinase (MMP) activity. Methods and results: Uptake of fluorescence-labeled LDL was analyzed using flow cytometry. Macrophages treated with imatinib showed a 23.5%, 27%, and 15% decrease in uptake of native LDL (p < 0.05), acetylated LDL (p < 0.01), and copper-modified oxidized LDL (p < 0.01), respectively. Gel based zymography showed that secretion and activity of MMP-2 and MMP-9 were inhibited by imatinib. Using GeneChip Whole Transcript Expression array analysis, no obvious gene candidates involved in the mechanisms of cholesterol metabolism or MMP regulation were found to be affected by imatinib. Instead, we found that imatinib up-regulated microRNA 155 (miR155) by 43.8% and down-regulated ADAM metallopeptidase domain 28 (ADAM28) by 41.4%. Both genes could potentially play an atheroprotective role and would be interesting targets in future studies. Conclusion: Our results indicate that imatinib causes post-translational inhibition with respect to cholesterol uptake and regulation of MMP-2 and MMP-9. More research is needed to further evaluate the role of imatinib in the regulation of other genes and processes. (c) 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.

  • 7.
    Hanssen, Anne-Merethe
    et al.
    UiT Arctic University of Norway, Norway.
    Kindlund, Bert
    University of Gothenburg, Sweden.
    Christian Stenklev, Niels
    UiT Arctic University of Norway, Norway.
    Furberg, Anne-Sofie
    University Hospital North Norway, Norway; UiT Arctic University of Norway, Norway.
    Fismen, Silje
    University Hospital North Norway, Norway.
    Slind Olsen, Renate
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Department Lab Med, Sweden.
    Johannessen, Mona
    UiT Arctic University of Norway, Norway.
    Ericson Sollid, Johanna Ulrica
    UiT Arctic University of Norway, Norway.
    Localization of Staphylococcus aureus in tissue from the nasal vestibule in healthy carriers2017In: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 17, article id 89Article in journal (Refereed)
    Abstract [en]

    Background: Colonization of the body is an important step in Staphylococcus aureus infection. S. aureus colonizes skin and mucous membranes in humans and several animal species. One important ecological niche of S. aureus is the anterior nares. More than 60% of the S. aureus in the nose are found in vestibulum nasi. Our aim was to describe the localization of S. aureus in nasal tissue from healthy carriers. Methods: Punch skin biopsies were taken from vestibulum nasi from healthy volunteers (S. aureus carriers and non-/intermittent carriers, n = 39) attending the population-based Tromso 6 study. The tissue samples were processed as frozen sections before immunostaining with a specific S. aureus antibody, and finally evaluated by a confocal laser-scanning microscope. Results: Our results suggest that S. aureus colonize both the upper and lower layers of the epidermis within the nasal epithelium of healthy individuals. The number of S. aureus in epidermis was surprisingly low. Intracellular localization of S. aureus in nasal tissue from healthy individuals was also detected. Conclusions: Knowledge of the exact localization of S. aureus in nasal tissue is important for the understanding of the host responses against S. aureus. Our results may have consequences for the eradication strategy of S. aureus in carriers, and further work can provide us with tools for targeted prevention of S. aureus colonisation and infection.

  • 8.
    Slind Olsen, Renate
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Circulating and genetic factors in colorectal cancer: Potential factors for establishing prognosis?2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Colorectal cancer (CRC) is defined as a cancer appearing in the colon or in the rectum. In Sweden, ~ 6300 individuals were diagnosed with the disease in 2014 and ~ 2550 individuals diagnosed with CRC die each year due to their cancer. Surgery is the main treatment option of CRC and a survival rate of ~ 10 % is estimated if distant metastases have developed. It is therefore of importance to find factors that may be useful together with tumour, node, metastasis (TNM) stage to establish early CRC diagnosis, prognosis and follow-up of CRC patients. The aim of this thesis was to study the possible association of CD93, PLA2G4C, PDGF-D and inflammatory cytokines with CRC disease progression.

    In a prospective study approach CD93 and PLA2G4C single nucleotide polymorphisms (SNPs) were of potential importance in CRC prognosis.

    The T/T genotype of CD93 was associated with an increased CD93 expression in CRC tissue. Further, CRC patients carrying this genotype were associated with disseminated CRC at diagnosis and a lower recurrence-free survival after surgery. The A allele of a SNP of PLA2G4C was a stronger predictor for CRC-specific mortality than the conventional risk factors used in the clinic for selection of TNM stage II patients for adjuvant treatment. This indicates that the T/T genotype of CD93 and the A allele of PLA2G4C may be potential genetic factors related to disease severity and spread. Furthermore, they distinguish CRC patients that may benefit from a more comprehensive follow-up and adjuvant treatment.

    To study the putative involvement of PDGF-D in CRC the effects of PDGF-D signalling was studied in vitro. PDGF-D signalling altered the expression of genes of importance in CRC carcinogenesis and proliferation which was blocked by imatinib, a tyrosine kinase inhibitor. This indicates that PDGF-D signalling may be an important pathway in CRC progression and a potential target in CRC treatment.

    The analysis of various inflammatory cytokines in plasma at diagnosis showed an association between high levels and increased total- or CRC-specific mortality two years after surgery. High levels of CCL1 and CCL24 was the only cytokines strongly correlated with a worse CRC prognosis after statistical adjustments and may be of interest for further evaluation.

    In conclusion, this thesis presents circulating and genetic factors such as CD93, PLA2G4C, PDGF-D, CCL1 and CCL24 that may be of importance in CRC progression and may be of clinical value together with TNM stage in establishing prognosis.

    List of papers
    1. CD93 gene polymorphism is associated with disseminated colorectal cancer
    Open this publication in new window or tab >>CD93 gene polymorphism is associated with disseminated colorectal cancer
    Show others...
    2015 (English)In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 30, no 7, p. 883-890Article in journal (Refereed) Published
    Abstract [en]

    Cluster of differentiation 93 (CD93) is involved in apoptosis and inflammation and has a suggested role in angiogenesis, and all of which are involved in the development and dissemination of cancer. We evaluated the expression of CD93 and the association with two single nucleotide polymorphisms (SNPs), rs2749812 and rs2749817, as possible biomarkers in colorectal cancer (CRC). Tissue levels and plasma levels of CD93 were measured using an enzyme-linked immunosorbent assay (ELISA). Expression of CD93 was determined by immunohistochemistry, western blot and gene expression analysis. Genotype frequencies were established for the SNPs by real-time polymerase chain reaction (PCR), and the association with tumour stage and survival was analysed. Total CD93 levels were 82 % higher (P less than 0.001) in tumours compared to matched normal tissues. Mean levels of soluble CD93 in plasma were 30 % lower (P less than 0.001) in the patients compared to the controls. The T/T genotype of SNP rs2749817 was more common in stage IV patients, with consequently higher risk of CRC death (T/T vs. C/C and C/T; hazard ratio (HR) = 1.73, 95 % confidence interval (CI) = 1.11-2.67, P = 0.014), and was associated with a higher risk of CRC recurrence after radical operation (T/T vs. C/C and C/T; HR = 2.07, CI = 1.22-3.51, P = 0.007). We showed that the T/T genotype of SNP rs2749817 is associated with disseminated cancer at diagnosis and an increased recurrence rate after radical operation. Patients with this genotype may benefit from early identification.

    Place, publisher, year, edition, pages
    Springer Verlag (Germany), 2015
    Keywords
    Biomarker; Colorectal cancer; Genotype; Prognosis; Single nucleotide polymorphism; Survival
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:liu:diva-120141 (URN)10.1007/s00384-015-2247-1 (DOI)000356350900003 ()26008729 (PubMedID)
    Note

    Funding Agencies|Foundation of Clinical Cancer Research, Jonkoping [110426-1]; Futurum; Academy of Healthcare; County Council of Jonkoping [FUTURUM-105891]; FORSS, the Research Council of Southeastern Sweden [FORSS-373251]

    Available from: 2015-07-14 Created: 2015-07-13 Last updated: 2017-12-04
    2. Prognostic significance of PLA2G4C gene polymorphism in patients with stage II colorectal cancer.
    Open this publication in new window or tab >>Prognostic significance of PLA2G4C gene polymorphism in patients with stage II colorectal cancer.
    Show others...
    2016 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 4, p. 474-479Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Phospholipase A2 Group IV C (PLA2G4C) catalyzes the release of certain fatty acids from phospholipids and plays a role in a range of physiological functions, such as remodeling of cell membranes and the production of prostaglandins. Furthermore, it has been proposed that PLA2G4C plays an important role in breast cancer cell chemotaxis. This study aimed to investigate the effect of a single nucleotide polymorphism (SNP) rs1549637 (T>A) of the PLA2G4C gene on the prognosis of colorectal cancer (CRC).

    MATERIAL AND METHODS: Whole blood DNA was extracted from 381 patients with CRC and 618 controls, and a TaqMan SNP genotyping assay was used to determine the distribution of the genotypes. Cancer-specific and disease-free survival was analyzed by Kaplan-Meier graphs and by uni- and multivariable Cox regression.

    RESULTS: The cancer-specific survival differed between the genotypes (p = 0.019) and the carriers of the A allele were associated with the highest risk of CRC death, with a hazard ratio (HR) of 1.72 [95% confidence interval (CI) 1.17-2.53, p = 0.006] compared with homozygous carriers of the T allele. This increased mortality in the carriers with the allele A was especially marked in stage II with an HR of 3.84 (95% CI 1.51-9.78, p = 0.005).

    CONCLUSION: The A allele in PLA2G4C SNP (rs1549637) is associated with a worse prognosis in patients with CRC, especially in stage II disease, and it could be a potential prognostic biomarker in the planning of individual adjuvant therapy in stage II patients.

    Place, publisher, year, edition, pages
    Taylor & Francis Group, 2016
    National Category
    Cancer and Oncology Cell and Molecular Biology
    Identifiers
    urn:nbn:se:liu:diva-125986 (URN)10.3109/0284186X.2015.1073350 (DOI)000372125400012 ()26364726 (PubMedID)
    Note

    Funding agencies: Futurum; Academy of Healthcare; Region Jonkoping County, Sweden; Foundation of Clinical Cancer Research, Jonkoping Sweden; University College of Health Sciences, Jonkoping, Sweden

    Available from: 2016-03-10 Created: 2016-03-10 Last updated: 2018-01-10
  • 9.
    Slind Olsen, Renate
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Laboratory Services, Ryhov County Hospital, Jönköping, Sweden.
    Andersson, Roland E
    Department of Surgery, Ryhov County Hospital, Jönköping Sweden.
    Zar, Niklas
    Department of Surgery, Ryhov County Hospital, Jönköping Sweden.
    Löfgren, Sture
    Department of Clinical Microbiology, Ryohov County Hospital, Jönköping .
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Matussek, Andreas
    Laboratory Services, Ryhov County Hospital, Jönköping, Sweden.
    Dimberg, Jan
    Natural Science and Biomedicine, University College of Health Sciences, Jönköping, Sweden.
    Prognostic significance of PLA2G4C gene polymorphism in patients with stage II colorectal cancer.2016In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 4, p. 474-479Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Phospholipase A2 Group IV C (PLA2G4C) catalyzes the release of certain fatty acids from phospholipids and plays a role in a range of physiological functions, such as remodeling of cell membranes and the production of prostaglandins. Furthermore, it has been proposed that PLA2G4C plays an important role in breast cancer cell chemotaxis. This study aimed to investigate the effect of a single nucleotide polymorphism (SNP) rs1549637 (T>A) of the PLA2G4C gene on the prognosis of colorectal cancer (CRC).

    MATERIAL AND METHODS: Whole blood DNA was extracted from 381 patients with CRC and 618 controls, and a TaqMan SNP genotyping assay was used to determine the distribution of the genotypes. Cancer-specific and disease-free survival was analyzed by Kaplan-Meier graphs and by uni- and multivariable Cox regression.

    RESULTS: The cancer-specific survival differed between the genotypes (p = 0.019) and the carriers of the A allele were associated with the highest risk of CRC death, with a hazard ratio (HR) of 1.72 [95% confidence interval (CI) 1.17-2.53, p = 0.006] compared with homozygous carriers of the T allele. This increased mortality in the carriers with the allele A was especially marked in stage II with an HR of 3.84 (95% CI 1.51-9.78, p = 0.005).

    CONCLUSION: The A allele in PLA2G4C SNP (rs1549637) is associated with a worse prognosis in patients with CRC, especially in stage II disease, and it could be a potential prognostic biomarker in the planning of individual adjuvant therapy in stage II patients.

  • 10.
    Slind Olsen, Renate
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Dept Lab Med, Sweden.
    Dimberg, Jan
    Jonkoping Univ, Sweden.
    Geffers, Robert
    Helmholtz Ctr Infect Res, Germany.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Possible Role and Therapeutic Target of PDGF-D Signalling in Colorectal Cancer2019In: Cancer Investigation, ISSN 0735-7907, E-ISSN 1532-4192, Vol. 37, no 2, p. 99-112Article in journal (Refereed)
    Abstract [en]

    Platelet-derived growth factor D (PDGF-D) has been shown to mediate cellular processes of importance in cancer progression. This study aimed to investigate the expression and putative involvement of PDGF-D signaling in colorectal carcinogenesis. PDGF-D was expressed in vascular endothelial cells in tumor and normal tissues. PDGF-D stimulation of cells altered genes of importance in carcinogenic processes. In addition, PDGF-D increased the proliferation rate while imatinib inhibited these effects. PDGF-D and its PDGF receptor beta (PDGFR-beta) are expressed in colorectal cancer and blockage of PDGF-D/PDGFR-beta signaling using tyrosine kinase inhibitors, such as imatinib, might be important in inhibiting tumor-promoting actions.

  • 11.
    Slind Olsen, Renate
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. County Hospital Ryhov, Sweden.
    Lindh, Mikael
    County Hospital Ryhov, Sweden.
    Vorkapic, Emina
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Andersson, Roland E.
    County Hospital Ryhov, Sweden.
    Zar, Niklas
    County Hospital Ryhov, Sweden.
    Lofgren, Sture
    County Hospital Ryhov, Sweden.
    Dimberg, Jan
    School Health Science, Sweden.
    Matussek, Andreas
    County Hospital Ryhov, Sweden.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    CD93 gene polymorphism is associated with disseminated colorectal cancer2015In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 30, no 7, p. 883-890Article in journal (Refereed)
    Abstract [en]

    Cluster of differentiation 93 (CD93) is involved in apoptosis and inflammation and has a suggested role in angiogenesis, and all of which are involved in the development and dissemination of cancer. We evaluated the expression of CD93 and the association with two single nucleotide polymorphisms (SNPs), rs2749812 and rs2749817, as possible biomarkers in colorectal cancer (CRC). Tissue levels and plasma levels of CD93 were measured using an enzyme-linked immunosorbent assay (ELISA). Expression of CD93 was determined by immunohistochemistry, western blot and gene expression analysis. Genotype frequencies were established for the SNPs by real-time polymerase chain reaction (PCR), and the association with tumour stage and survival was analysed. Total CD93 levels were 82 % higher (P less than 0.001) in tumours compared to matched normal tissues. Mean levels of soluble CD93 in plasma were 30 % lower (P less than 0.001) in the patients compared to the controls. The T/T genotype of SNP rs2749817 was more common in stage IV patients, with consequently higher risk of CRC death (T/T vs. C/C and C/T; hazard ratio (HR) = 1.73, 95 % confidence interval (CI) = 1.11-2.67, P = 0.014), and was associated with a higher risk of CRC recurrence after radical operation (T/T vs. C/C and C/T; HR = 2.07, CI = 1.22-3.51, P = 0.007). We showed that the T/T genotype of SNP rs2749817 is associated with disseminated cancer at diagnosis and an increased recurrence rate after radical operation. Patients with this genotype may benefit from early identification.

  • 12.
    Slind Olsen, Renate
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Department Lab Med, Sweden.
    Nijm, Johnny
    Division of Medical Diagnostics, Department of Clinical Physiology, Region Jönköping County, Jönköping, Sweden.
    Andersson, Roland
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Department of Surgery, Region Jönköping County, Sweden.
    Dimberg, Jan
    Jonköping University, Sweden.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Circulating inflammatory factors associated with worse long-term prognosis in colorectal cancer2017In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 23, no 34, p. 6212-6219Article in journal (Refereed)
    Abstract [en]

    AIM To investigate association of circulating inflammatory factors at the time of colorectal cancer (CRC) surgery with survival. METHODS Plasma levels from 174 CRC patients (69 females and 105 men), with median age 70 years (range 29-90), localized in the colon (n = 105) or rectum (n = 69), with stage. (n = 24), stage. (n = 54), stage. (n = 67) and stage. (n = 29) were measured using commercially available Bio-Plex Pro (TM) Human Chemokine Panel 40-Plex, including 40 different chemokines, cytokines and interleukins. The prognostic association of each inflammatory factor was analysed as CRC-specific and total mortality. RESULTS Out of 174 patients, 66 died during the follow-up, 40 because of CRC specific mortality. High tertile levels of 8 factors were significantly associated with increased CRC-specific mortality, of which CCL1, CCL20, CCL24, CX3CL1, IL-4 and TNF-alpha remained significant in a multivariate Cox regression analysis. High tertile levels of 14 factors were associated with increased total mortality, of which CCL1, CCL15, CCL20, CX3CL1, CXCL13, IFN-gamma, IL-2, IL-4 and IL-10 remained significant after adjustment for clinical covariates. For most of the inflammatory factors the association between higher tertile levels and an increased mortality in general appeared two years after surgery. High tertile levels of TNF-alpha and CCL24 were exclusively associated with CRC-specific mortality. The distribution of these factors were not associated with TNM stage with exception for CCL20. CONCLUSION High plasma levels of inflammatory factors are associated with increased risk of mortality among CRC patients and could be potential biomarkers for revealing prognosis.

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