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Nyström, Hanna
Publications (10 of 15) Show all publications
Ward, H. A., Murphy, N., Weiderpass, E., Leitzmann, M. F., Aglago, E., Gunter, M. J., . . . Cross, A. J. (2019). Gallstones and incident colorectal cancer in a large pan-European cohort study. International Journal of Cancer, 145(6), 1510-1516
Open this publication in new window or tab >>Gallstones and incident colorectal cancer in a large pan-European cohort study
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2019 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 145, no 6, p. 1510-1516Article in journal (Refereed) Published
Abstract [en]

Gallstones, a common gastrointestinal condition, can lead to several digestive complications and can result in inflammation. Risk factors for gallstones include obesity, diabetes, smoking and physical inactivity, all of which are known risk factors for colorectal cancer (CRC), as is inflammation. However, it is unclear whether gallstones are a risk factor for CRC. We examined the association between history of gallstones and CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a prospective cohort of over half a million participants from ten European countries. History of gallstones was assessed at baseline using a self‐reported questionnaire. The analytic cohort included 334,986 participants; a history of gallstones was reported by 3,917 men and 19,836 women, and incident CRC was diagnosed among 1,832 men and 2,178 women (mean follow‐up: 13.6 years). Hazard ratios (HR) and 95% confidence intervals (CI) for the association between gallstones and CRC were estimated using Cox proportional hazards regression models, stratified by sex, study centre and age at recruitment. The models were adjusted for body mass index, diabetes, alcohol intake and physical activity. A positive, marginally significant association was detected between gallstones and CRC among women in multivariable analyses (HR = 1.14, 95%CI 0.99–1.31, p = 0.077). The relationship between gallstones and CRC among men was inverse but not significant (HR = 0.81, 95%CI 0.63–1.04, p = 0.10). Additional adjustment for details of reproductive history or waist circumference yielded minimal changes to the observed associations. Further research is required to confirm the nature of the association between gallstones and CRC by sex.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
Keywords
Gallstones, colorectal cancer, EPIC, cohort
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-162390 (URN)10.1002/ijc.32090 (DOI)000476557000007 ()30585640 (PubMedID)2-s2.0-85059850802 (Scopus ID)
Available from: 2019-08-20 Created: 2019-08-20 Last updated: 2019-08-20Bibliographically approved
Vaniotis, G., Rayes, R. F., Qi, S., Milette, S., Wang, N., Perrino, S., . . . Brodt, P. (2018). Collagen IV-conveyed signals can regulate chemokine production and promote liver metastasis. Oncogene, 37(28), 3790-3805
Open this publication in new window or tab >>Collagen IV-conveyed signals can regulate chemokine production and promote liver metastasis
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2018 (English)In: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 37, no 28, p. 3790-3805Article in journal (Refereed) Published
Abstract [en]

Liver metastases remain a major cause of death from gastrointestinal tract cancers as well as from other malignancies such as breast and lung carcinomas and melanoma. Understanding the underlying biology is essential for the design of effective targeted therapies. We previously reported that collagen IV α1/α2 overexpression in non-metastatic lung carcinoma (M27colIV) cells increased their metastatic ability, specifically to the liver and documented high collagen IV levels in surgical resections of liver metastases from diverse tumor types. Here, we aimed to elucidate the functional relevance of collagen IV to metastatic outgrowth in the liver. Gene expression profiling revealed in M27colIVcells significant increases in the expression of chemokines CCL5 (5.7-fold) and CCL7 (2.6-fold) relative to wild-type cells, and this was validated by qPCR and western blotting. Similarly, in human colon carcinoma KM12C and KM12SM cells with divergent liver-colonizing potentials, CCL7 and CCL5 production correlated with type IV collagen expression and the metastatic phenotype. CCL7 silencing by short hairpin RNA (shRNA) reduced experimental liver metastasis in both cell types, whereas CCL5 silencing reduced metastasis of M27colIV cells, implicating these cytokines in metastatic expansion in the liver. Subsequent functional analyses implicated both MEK/ERK and PI3K signaling upstream of CCL7 upregulation and identified CCL7 (but not CCL5) as a critical migration/invasion factor, acting via the chemokine receptor CCR3. Chemokine CCL5 was identified as a regulator of the T-cell immune response in the liver. Loss of CCL7 in KM12SM cells was also associated with altered E-cadherin and reduced vimentin and Snail expression, implicating it in epithelial-to-mesenchymal transition in these cells. Moreover, in clinical specimens of colon cancer liver metastases analyzed by immunohistochemistry, CCL5 and CCL7 levels paralleled those of collagen IV. The results identify the chemokines CCL5 and CCL7 as type IV collagen-regulated genes that promote liver metastasis by distinct and complementary mechanisms.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-150724 (URN)10.1038/s41388-018-0242-z (DOI)000438465600003 ()29651051 (PubMedID)2-s2.0-85045252604 (Scopus ID)
Available from: 2018-08-29 Created: 2018-08-29 Last updated: 2018-08-29Bibliographically approved
Franklin, O., Jonsson, P., Billing, O., Lundberg, E., Öhlund, D., Nyström, H., . . . Sund, M. (2018). Plasma micro-RNA alterations appear late in pancreatic cancer. Annals of Surgery, 267(4), 775-781
Open this publication in new window or tab >>Plasma micro-RNA alterations appear late in pancreatic cancer
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2018 (English)In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 267, no 4, p. 775-781Article in journal (Refereed) Published
Abstract [en]

Objectives: The aim of this research was to study whether plasma microRNAs (miRNA) can be used for early detection of pancreatic cancer (PC) by analyzing prediagnostic plasma samples collected before a PC diagnosis. Background: PC has a poor prognosis due to late presenting symptoms and early metastasis. Circulating miRNAs are altered in PC at diagnosis but have not been evaluated in a prediagnostic setting. Methods: We first performed an initial screen using a panel of 372 miRNAs in a retrospective case-control cohort that included early-stage PC patients and healthy controls. Significantly altered miRNAs at diagnosis were then measured in an early detection case-control cohort wherein plasma samples in the cases are collected before a PC diagnosis. Carbohydrate antigen 19–9 (Ca 19–9) levels were measured in all samples for comparison. Results: Our initial screen, including 23 stage I-II PC cases and 22 controls, revealed 15 candidate miRNAs that were differentially expressed in plasma samples at PC diagnosis. We combined all 15 miRNAs into a multivariate statistical model, which outperformed Ca 19–9 in receiver-operating characteristics analysis. However, none of the candidate miRNAs, individually or in combination, were significantly altered in prediagnostic plasma samples from 67 future PC patients compared with 132 matched controls. In comparison, Ca 19–9 levels were significantly higher in the cases at <5 years before diagnosis. Conclusion: Plasma miRNAs are altered in PC patients at diagnosis, but the candidate miRNAs found in this study appear late in the course of the disease and cannot be used for early detection of the disease.

Keywords
blood samples, early detection, micro-RNA, miRNA, pancreatic cancer
National Category
Clinical Laboratory Medicine Chemical Sciences
Identifiers
urn:nbn:se:umu:diva-127998 (URN)10.1097/SLA.0000000000002124 (DOI)000435846900046 ()28425921 (PubMedID)2-s2.0-85044257717 (Scopus ID)
Note

Originally included in thesis in manuscript form.

Available from: 2016-11-21 Created: 2016-11-21 Last updated: 2018-09-27Bibliographically approved
van Dam, P.-J., van der Stok, E. P., Teuwen, L.-A., Van den Eynden, G. G., Illemann, M., Frentzas, S., . . . Vermeulen, P. B. (2017). International consensus guidelines for scoring the histopathological growth patterns of liver metastasis. British Journal of Cancer, 117(10), 1427-1441
Open this publication in new window or tab >>International consensus guidelines for scoring the histopathological growth patterns of liver metastasis
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2017 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 117, no 10, p. 1427-1441Article in journal (Refereed) Published
Abstract [en]

Background: Liver metastases present with distinct histopathological growth patterns (HGPs), including the desmoplastic, pushing and replacement HGPs and two rarer HGPs. The HGPs are defined owing to the distinct interface between the cancer cells and the adjacent normal liver parenchyma that is present in each pattern and can be scored from standard haematoxylin-and-eosin-stained (H&E) tissue sections. The current study provides consensus guidelines for scoring these HGPs.

Methods: Guidelines for defining the HGPs were established by a large international team. To assess the validity of these guidelines, 12 independent observers scored a set of 159 liver metastases and interobserver variability was measured. In an independent cohort of 374 patients with colorectal liver metastases (CRCLM), the impact of HGPs on overall survival after hepatectomy was determined.

Results: Good-to-excellent correlations (intraclass correlation coefficient >0.5) with the gold standard were obtained for the assessment of the replacement HGP and desmoplastic HGP. Overall survival was significantly superior in the desmoplastic HGP subgroup compared with the replacement or pushing HGP subgroup (P=0.006).

Conclusions: The current guidelines allow for reproducible determination of liver metastasis HGPs. As HGPs impact overall survival after surgery for CRCLM, they may serve as a novel biomarker for individualised therapies.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2017
Keywords
liver metastasis, colorectal cancer, breast cancer, vessel co-option, angiogenesis, tumour croenvironment, prognostic factor
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-142243 (URN)10.1038/bjc.2017.334 (DOI)000414550300005 ()
Available from: 2017-12-11 Created: 2017-12-11 Last updated: 2018-06-09Bibliographically approved
Murphy, N., Cross, A. J., Abubakar, M., Jenab, M., Aleksandrova, K., Boutron-Ruault, M.-C., . . . Gunter, M. J. (2016). A Nested Case-Control Study of Metabolically Defined Body Size Phenotypes and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). PLoS Medicine, 13(4), Article ID e1001988.
Open this publication in new window or tab >>A Nested Case-Control Study of Metabolically Defined Body Size Phenotypes and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)
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2016 (English)In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 13, no 4, article id e1001988Article in journal (Refereed) Published
Abstract [en]

Background Obesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia) have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic) overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown.

Methods and Findings The association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI) measurements to create four metabolic health/body size phenotype categories: (1) metabolically healthy/normal weight (BMI < 25 kg/m(2)), (2) metabolically healthy/overweight (BMI >= 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI < 25 kg/m2), and (4) metabolically unhealthy/overweight (BMI >= 25 kg/m2). Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [>= 80 cm for women and >= 94 cm for men]) were used (instead of BMI) to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of <0.05 was considered statistically significant. In multivariable-adjusted conditional logistic regression models with BMI used to define adiposity, compared with metabolically healthy/normal weight individuals, we observed a higher colorectal cancer risk among metabolically unhealthy/normal weight (odds ratio [OR] = 1.59, 95% CI 1.10-2.28) and metabolically unhealthy/overweight (OR = 1.40, 95% CI 1.01-1.94) participants, but not among metabolically healthy/overweight individuals (OR = 0.96, 95% CI 0.65-1.42). Among the overweight individuals, lower colorectal cancer risk was observed for metabolically healthy/overweight individuals compared with metabolically unhealthy/overweight individuals (OR = 0.69, 95% CI 0.49-0.96). These associations were generally consistent when waist circumference was used as the measure of adiposity. To our knowledge, there is no universally accepted clinical definition for using C-peptide level as an indication of hyperinsulinaemia. Therefore, a possible limitation of our analysis was that the classification of individuals as being hyperinsulinaemic-based on their C-peptide level-was arbitrary. However, when we used quartiles or the median of C-peptide, instead of tertiles, as the cut-point of hyperinsulinaemia, a similar pattern of associations was observed.

Conclusions These results support the idea that individuals with the metabolically healthy/overweight phenotype (with normal insulin levels) are at lower colorectal cancer risk than those with hyperinsulinaemia. The combination of anthropometric measures with metabolic parameters, such as C-peptide, may be useful for defining strata of the population at greater risk of colorectal cancer.

National Category
Cancer and Oncology Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-121593 (URN)10.1371/journal.pmed.1001988 (DOI)000375096900002 ()27046222 (PubMedID)
Available from: 2016-06-22 Created: 2016-06-03 Last updated: 2018-06-07Bibliographically approved
Frentzas, S., Simoneau, E., Bridgeman, V. L., Vermeulen, P. B., Foo, S., Kostaras, E., . . . Reynolds, A. R. (2016). Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases. Nature Medicine, 22(11), 1294-1302
Open this publication in new window or tab >>Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases
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2016 (English)In: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 22, no 11, p. 1294-1302Article in journal (Refereed) Published
Abstract [en]

The efficacy of angiogenesis inhibitors in cancer is limited by resistance mechanisms that are poorly understood. Notably, instead of through the induction of angiogenesis, tumor vascularization can occur through the nonangiogenic mechanism of vessel co-option. Here we show that vessel co-option is associated with a poor response to the anti-angiogenic agent bevacizumab in patients with colorectal cancer liver metastases. Moreover, we find that vessel co-option is also prevalent in human breast cancer liver metastases, a setting in which results with anti-angiogenic therapy have been disappointing. In preclinical mechanistic studies, we found that cancer cell motility mediated by the actin-related protein 2/3 complex (Arp2/3) is required for vessel co-option in liver metastases in vivo and that, in this setting, combined inhibition of angiogenesis and vessel co-option is more effective than the inhibition of angiogenesis alone. Vessel co-option is therefore a clinically relevant mechanism of resistance to anti-angiogenic therapy and combined inhibition of angiogenesis and vessel co-option might be a warranted therapeutic strategy.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-128965 (URN)10.1038/nm.4197 (DOI)000387302300022 ()27748747 (PubMedID)
Available from: 2016-12-30 Created: 2016-12-20 Last updated: 2018-06-09Bibliographically approved
Nyström, H., Tavelin, B., Björklund, M., Naredi, P. & Sund, M. (2015). Improved tumour marker sensitivity in detecting colorectal liver metastases by combined type IV collagen and CEA measurement. Tumor Biology, 36(12), 9839-9847
Open this publication in new window or tab >>Improved tumour marker sensitivity in detecting colorectal liver metastases by combined type IV collagen and CEA measurement
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2015 (English)In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 36, no 12, p. 9839-9847Article in journal (Refereed) Published
Abstract [en]

Carcinoembryonic antigen (CEA) is the best circulating tumour marker for colorectal liver metastasis (CLM) but has suboptimal sensitivity and specificity. Circulating type IV collagen (COLIV) is a new potential CLM marker. Here, COLIV and CEA were measured in patients with resectable CLM. COLIV levels were also related to the type of CLM. The prognostic value of these markers and the type of CLM on survival was evaluated. Preoperative plasma samples (n = 94) from patients (n = 85) with CLM undergoing liver resection were used. Seven patients underwent repeated liver resection. Samples from 118 healthy individuals served as control. Samples after liver resection (n = 27) were analysed and related to recurrence. COLIV and CEA levels were analysed, and the type of CLM was classified using paraffinated tissue. Results were analysed by logistic regression and receiver operating characteristic (ROC) curve analysis. CLM patients had significantly elevated levels of COLIV compared to controls (p = 0.001). The sensitivity of COLIV was not better than CEA, but improved sensitivity for detecting CLM was observed with a combination of the two markers compared to using either marker alone (p = 0.001). Circulating COLIV was elevated in 81 % and CEA in 56 % of CLM patients at diagnosis, and high marker levels were related to poor survival. In follow-up samples (n = 27), patients with CLM recurrence (n = 14) had significantly elevated COLIV levels compared to patients without postoperative recurrence (n = 10) (p = 0.001). COLIV is a promising tumour marker for CLM and can possibly be used to detect postoperative CLM recurrence. The combination of COLIV and CEA is superior to either marker alone in detecting CLM.

Place, publisher, year, edition, pages
Springer, 2015
Keywords
Colorectal liver metastases, Circulating biomarkers, CEA, Type IV collagen, Extracellular matrix
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-114582 (URN)10.1007/s13277-015-3729-z (DOI)000367329300082 ()26162539 (PubMedID)
Available from: 2016-02-16 Created: 2016-01-25 Last updated: 2018-06-07Bibliographically approved
Nimptsch, K., Aleksandrova, K., Boeing, H., Janke, J., Lee, Y.-A., Jenab, M., . . . Pischon, T. (2015). Plasma fetuin-A concentration, genetic variation in the AHSG gene and risk of colorectal cancer. International Journal of Cancer, 137(4), 911-920
Open this publication in new window or tab >>Plasma fetuin-A concentration, genetic variation in the AHSG gene and risk of colorectal cancer
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2015 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 137, no 4, p. 911-920Article in journal (Refereed) Published
Abstract [en]

Fetuin-A, also referred to as alpha 2-Heremans-Schmid glycoprotein (AHSG), is a liver protein known to inhibit insulin actions. Hyperinsulinemia is a possible risk factor for colorectal cancer; however, the role of fetuin-A in the development of colorectal cancer is unclear. We investigated the association between circulating fetuin-A and colorectal cancer risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Fetuin-A concentrations were measured in prediagnostic plasma samples from 1,367 colorectal cancer cases and 1,367 matched controls. In conditional logistic regression models adjusted for potential confounders, the estimated relative risk (95% confidence interval) of colorectal cancer per 40 mg/mL higher fetuin-A concentrations (approximately one standard deviation) was 1.13 (1.02-1.24) overall, 1.21 (1.05-1.39) in men, 1.06 (0.93-1.22) in women, 1.13 (1.00-1.27) for colon cancer and 1.12 (0.94-1.32) for rectal cancer. To improve causal inference in a Mendelian Randomization approach, five tagging single nucleotide polymorphisms of the AHSG gene were genotyped in a subset of 456 case-control pairs. The AHSG allele-score explained 21% of the interindividual variation in plasma fetuin-A concentrations. In instrumental variable analysis, genetically raised fetuin-A was not associated with colorectal cancer risk (relative risk per 40 mg/mL genetically determined higher fetuin-A was 0.98, 95% confidence interval: 0.73-1.33). The findings of our study indicate a modest linear association between fetuin-A concentrations and risk of colorectal cancer but suggest that fetuin-A may not be causally related to colorectal cancer development.

Keywords
fetuin-A, AHSG, colorectal cancer
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-106308 (URN)10.1002/ijc.29448 (DOI)000356428400017 ()25611809 (PubMedID)
Available from: 2015-07-20 Created: 2015-07-10 Last updated: 2018-06-07Bibliographically approved
Kong, S. Y., Takeuchi, M., Hyogo, H., McKeown-Eyssen, G., Yamagishi, S.-I., Chayama, K., . . . Bruce, W. R. (2015). The Association between Glyceraldehyde-Derived Advanced Glycation End-Products and Colorectal Cancer Risk. Cancer Epidemiology, Biomarkers and Prevention, 24(12), 1855-1863
Open this publication in new window or tab >>The Association between Glyceraldehyde-Derived Advanced Glycation End-Products and Colorectal Cancer Risk
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2015 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 24, no 12, p. 1855-1863Article in journal (Refereed) Published
Abstract [en]

Background: A large proportion of colorectal cancers are thought to be associated with unhealthy dietary and lifestyle exposures, particularly energy excess, obesity, hyperinsulinemia, and hyperglycemia. It has been suggested that these processes stimulate the production of toxic reactive carbonyls from sugars such as glyceraldehyde. Glyceraldehyde contributes to the production of a group of compounds known as glyceraldehyde-derived advanced glycation end-products (glycer-AGEs), which may promote colorectal cancer through their proinflammatory and pro-oxidative properties. The objective of this study nested within a prospective cohort was to explore the association of circulating glycer-AGEs with risk of colorectal cancer. Methods: A total of 1,055 colorectal cancer cases (colon n = 659; rectal n = 396) were matchced (1: 1) to control subjects. Circulating glycer-AGEs were measured by a competitive ELISA. Multivariable conditional logistic regression models were used to calculate ORs and 95% confidence intervals (95% CI), adjusting for potential confounding factors, including smoking, alcohol, physical activity, body mass index, and diabetes status. Results: Elevated glycer-AGEs levels were not associated with colorectal cancer risk (highest vs. lowest quartile, 1.10; 95% CI, 0.82-1.49). Subgroup analyses showed possible divergence by anatomical subsites (OR for colon cancer, 0.83; 95% CI, 0.571.22; OR for rectal cancer, 1.90; 95% CI, 1.14-3.19; Pheterogeneity = 0.14). Conclusions: In this prospective study, circulating glycer-AGEs were not associated with risk of colon cancer, but showed a positive association with the risk of rectal cancer. Impact: Further research is needed to clarify the role of toxic products of carbohydrate metabolism and energy excess in colorectal cancer development. 

National Category
Cancer and Oncology Occupational Health and Environmental Health
Identifiers
urn:nbn:se:umu:diva-113848 (URN)10.1158/1055-9965.EPI-15-0422 (DOI)000366129100007 ()26404963 (PubMedID)
Available from: 2016-03-30 Created: 2016-01-04 Last updated: 2018-06-07Bibliographically approved
Norgren, N., Olsson, M., Nyström, H., Ericzon, B. G., de Tayrac, M., Genin, E., . . . Suhr, O. B. (2014). Gene expression profile in hereditary transthyretin amyloidosis: differences in targeted and source organs. Amyloid: Journal of Protein Folding Disorders, 21(2), 113-119
Open this publication in new window or tab >>Gene expression profile in hereditary transthyretin amyloidosis: differences in targeted and source organs
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2014 (English)In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 21, no 2, p. 113-119Article in journal (Refereed) Published
Abstract [en]

Introduction: Hereditary transthyretin amyloidosis (ATTR) is a genetic disease caused by a point mutation in the TTR gene that causes the liver to produce an unstable TTR protein. The most effective treatment has been liver transplantation in order to replace the variant TTR producing liver with one that produces only wild-type TTR. ATTR amyloidosis patients' livers are reused for liver sick patients, i.e. the Domino procedure. However, recent findings have demonstrated that ATTR amyloidosis can develop in the recipients within 7-8 years. The aim of this study was to elucidate how the genetic profile of the liver is affected by the disease, and how amyloid deposits affect target tissue. Methods: Gene expression analysis was used to unravel the genetic profiles of Swedish ATTR V30M patients and controls. Biopsies from adipose tissue and liver were examined. Results and Conclusions: ATTR amyloid patients' gene expression profile of the main source organ, the liver, differed markedly from that of the controls, whereas the target organs' gene expression profiles were not markedly altered in the ATTR amyloid patients compared to those of the controls. An impaired ER/protein folding pathway might suggest ER overload due to mutated TTR protein.

Keywords
Adipose tissue, familial amyloidosis, liver tissue, PCA, Simca, V30M
National Category
Medical Genetics
Identifiers
urn:nbn:se:umu:diva-90410 (URN)10.3109/13506129.2014.894908 (DOI)000336146700007 ()
Note

Originally included in thesis in manuscript form.

Available from: 2014-07-10 Created: 2014-06-23 Last updated: 2018-06-07Bibliographically approved
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