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Thysell, Elin
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Publications (10 of 58) Show all publications
Wikström, P., Bergh, A., Josefsson, A., Thysell, E. & Welén, K. (2024). Molekylära subtyper och avancerad prostatacancer: nya möjligheter för anpassad behandling: [Molecular subtypes provide possibilities for precision medicine in a advanced prostate cancer]. Läkartidningen, 121, Article ID 23179.
Open this publication in new window or tab >>Molekylära subtyper och avancerad prostatacancer: nya möjligheter för anpassad behandling: [Molecular subtypes provide possibilities for precision medicine in a advanced prostate cancer]
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2024 (Swedish)In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 121, article id 23179Article, review/survey (Refereed) Published
Abstract [en]

Increased molecular knowledge makes it possible to consider not only genetic defects but also expression profiles for precision medicine in advanced prostate cancer. Several prognostic and treatment-predictive classifiers for prostate cancer have been described, such as Prolaris, OncotypeDx, Decipher, Prostatype, PAM50, PCS1-2, and MetA-C, which all build upon transcript profiles. In research studies, the MetA-C classifier has shown clear prognostic information for patients with metastatic disease, in relation to outcome after androgen receptor targeting therapies, and so has immunohistochemical evaluation of tumor cell proliferation (Ki67) and PSA expression. Unfortunately, methods within clinical routine today do not allow molecular subclassification of prostate cancer. To enable comparison of the most promising treatment-predictive biomarkers and to evaluate the health economic value of implementing such precision medicine for prostate cancer, a prospective study is being planned as a joint initiative in Sweden that aims to evaluate and validate biomarkers and to establish a study platform for adaptive biomarker-driven clinical trials (sprintr.se).

Place, publisher, year, edition, pages
Läkartidningen Förlag AB, 2024
National Category
Urology and Nephrology Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-224113 (URN)2-s2.0-85191380918 (Scopus ID)
Available from: 2024-05-13 Created: 2024-05-13 Last updated: 2024-05-13Bibliographically approved
Wänman, J., Abul-Kasim, K., Semenas, J., Thysell, E., Bergh, A., Wikström, P. & Crnalic, S. (2023). A novel radiographic pattern related to poor prognosis in patients with prostate cancer with metastatic spinal cord compression. European Urology Open Science, 48, 44-53
Open this publication in new window or tab >>A novel radiographic pattern related to poor prognosis in patients with prostate cancer with metastatic spinal cord compression
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2023 (English)In: European Urology Open Science, ISSN 2666-1691, E-ISSN 2666-1683, Vol. 48, p. 44-53Article in journal (Refereed) Published
Abstract [en]

Background: Prostate cancer spinal bone metastases can have a radiographic profile that mimics multiple myeloma.

Objective: To analyse the presence and prognostic value of myeloma-like prostate cancer bone metastases and its relation to known clinical, molecular, and morphological prognostic markers.

Design, setting, and participants: A cohort of 110 patients with prostate cancer who underwent surgery for metastatic spinal cord compression (MSCC) was analysed. Spinal bone metastases were classified as myeloma like (n = 20) or non–myeloma like (n = 90) based on magnetic resonance imaging prior to surgery. An immunohistochemical analysis of metastasis samples was performed to assess tumour cell proliferation (percentage of Ki67-positive cells) and the expression levels of prostate-specific antigen (PSA) and androgen receptor (AR). The metastasis subtypes MetA, MetB, and MetC were determined from transcriptomic profiling.

Outcome measurements and statistical analysis: Survival curves were compared with the log-rank test. Univariate and multivariate Cox proportional hazard models were used to assess the effects of prognostic variables. Groups were compared using the Mann-Whitney U test for continuous variables and the chi-square test for categorical variables.

Results and limitations: Patients with the myeloma-like metastatic pattern had median survival after surgery for MSCC of 1.7 (range 0.1–33) mo, while the median survival period of those with the non–myeloma-like pattern was 13 (range 0–140) mo (p < 0.001). The myeloma-like appearance had an independent prognostic value for the risk of death after MSCC surgery (adjusted hazard ratio 2.4, p = 0.012). Postoperative neurological function was significantly reduced in the myeloma-like group. No association was found between the myeloma-like pattern and morphological markers of known relevance for this patient group: the transcriptomic subtypes MetA, MetB, and MetC; tumour cell proliferation; and AR and PSA expression.

Conclusions: A myeloma-like metastatic pattern identifies an important subtype of metastatic prostate cancer associated with poor survival and neurological outcomes after surgery for MSCC.

Patient summary: This study describes a novel radiographic pattern of prostate cancer bone metastases and its relation to poor patient prognosis.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
Metastatic spinal cord, compression, Myeloma-like prostate cancer, bone metastases, Prostate cancer
National Category
Orthopaedics
Identifiers
urn:nbn:se:umu:diva-202101 (URN)10.1016/j.euros.2022.12.004 (DOI)000973999000001 ()2-s2.0-85144765610 (Scopus ID)
Funder
Swedish Cancer SocietyCancerforskningsfonden i NorrlandRegion Västerbotten
Available from: 2023-01-02 Created: 2023-01-02 Last updated: 2023-09-05Bibliographically approved
Watts, E. L., Perez-Cornago, A., Fensom, G. K., Smith-Byrne, K., Noor, U., Andrews, C. D., . . . The PRACTICAL Consortium, CRUK, BPC3, CAPS, PEGASUS, . (2023). Circulating insulin-like growth factors and risks of overall, aggressive and early-onset prostate cancer: a collaborative analysis of 20 prospective studies and Mendelian randomization analysis. International Journal of Epidemiology, 52(1), 71-86
Open this publication in new window or tab >>Circulating insulin-like growth factors and risks of overall, aggressive and early-onset prostate cancer: a collaborative analysis of 20 prospective studies and Mendelian randomization analysis
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2023 (English)In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 52, no 1, p. 71-86Article in journal (Refereed) Published
Abstract [en]

Background: Previous studies had limited power to assess the associations of circulating insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with clinically relevant prostate cancer as a primary endpoint, and the association of genetically predicted IGF-I with aggressive prostate cancer is not known. We aimed to investigate the associations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 concentrations with overall, aggressive and early-onset prostate cancer.

Methods: Prospective analysis of biomarkers using the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset (up to 20 studies, 17 009 prostate cancer cases, including 2332 aggressive cases). Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression. For IGF-I, two-sample Mendelian randomization (MR) analysis was undertaken using instruments identified using UK Biobank (158 444 men) and outcome data from PRACTICAL (up to 85 554 cases, including 15 167 aggressive cases). Additionally, we used colocalization to rule out confounding by linkage disequilibrium.

Results: In observational analyses, IGF-I was positively associated with risks of overall (OR per 1 SD = 1.09: 95% CI 1.07, 1.11), aggressive (1.09: 1.03, 1.16) and possibly early-onset disease (1.11: 1.00, 1.24); associations were similar in MR analyses (OR per 1 SD = 1.07: 1.00, 1.15; 1.10: 1.01, 1.20; and 1.13; 0.98, 1.30, respectively). Colocalization also indicated a shared signal for IGF-I and prostate cancer (PP4: 99%). Men with higher IGF-II (1.06: 1.02, 1.11) and IGFBP-3 (1.08: 1.04, 1.11) had higher risks of overall prostate cancer, whereas higher IGFBP-1 was associated with a lower risk (0.95: 0.91, 0.99); these associations were attenuated following adjustment for IGF-I.

Conclusions: These findings support the role of IGF-I in the development of prostate cancer, including for aggressive disease.

Place, publisher, year, edition, pages
Oxford University Press, 2023
Keywords
aggressive prostate cancer, Insulin-like growth factor-I, international consortia, Mendelian randomization, prospective analysis, prostate cancer
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-211993 (URN)10.1093/ije/dyac124 (DOI)000813479800001 ()35726641 (PubMedID)2-s2.0-85137773721 (Scopus ID)
Available from: 2023-07-12 Created: 2023-07-12 Last updated: 2024-03-26Bibliographically approved
Almanza-Aguilera, E., Guiñón-Fort, D., Perez-Cornago, A., Martínez-Huélamo, M., Andrés-Lacueva, C., Tjønneland, A., . . . Zamora-Ros, R. (2023). Intake of the total, classes, and subclasses of (poly)phenols and risk of prostate cancer: a prospective analysis of the EPIC study. Cancers, 15(16), Article ID 4067.
Open this publication in new window or tab >>Intake of the total, classes, and subclasses of (poly)phenols and risk of prostate cancer: a prospective analysis of the EPIC study
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2023 (English)In: Cancers, ISSN 2072-6694, Vol. 15, no 16, article id 4067Article in journal (Refereed) Published
Abstract [en]

Existing epidemiological evidence regarding the potential role of (poly)phenol intake in prostate cancer (PCa) risk is scarce and, in the case of flavonoids, it has been suggested that their intake may increase PCa risk. We investigated the associations between the intake of the total and individual classes and subclasses of (poly)phenols and the risk of PCa, including clinically relevant subtypes. The European Prospective Investigation into Cancer and Nutrition (EPIC) cohort included 131,425 adult men from seven European countries. (Poly)phenol intake at baseline was assessed by combining validated center/country-specific dietary questionnaires and the Phenol-Explorer database. Multivariable-adjusted Cox proportional hazards models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI). In total, 6939 incident PCa cases (including 3501 low-grade and 710 high-grade, 2446 localized and 1268 advanced, and 914 fatal Pca cases) were identified during a mean follow-up of 14 years. No associations were observed between the total intake of (poly)phenols and the risk of PCa, either overall (HRlog2 = 0.99, 95% CI 0.94–1.04) or according to PCa subtype. Null associations were also found between all classes (phenolic acids, flavonoids, lignans, and stilbenes) and subclasses of (poly)phenol intake and the risk of PCa, overall and according to PCa subtype. The results of the current large prospective cohort study do not support any association between (poly)phenol intake and PCa incidence.

Place, publisher, year, edition, pages
MDPI, 2023
Keywords
cohort, diet, EPIC, intake, polyphenols, prostate cancer
National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-214056 (URN)10.3390/cancers15164067 (DOI)2-s2.0-85168888820 (Scopus ID)
Funder
Swedish Cancer SocietySwedish Research CouncilRegion SkåneRegion Västerbotten
Available from: 2023-09-06 Created: 2023-09-06 Last updated: 2024-03-26Bibliographically approved
Järemo, H., Semenas, J., Halin Bergström, S., Lundholm, M., Thysell, E., Widmark, A., . . . Wikström, P. (2023). Investigating microRNA Profiles in Prostate Cancer Bone Metastases and Functional Effects of microRNA-23c and microRNA-4328. Cancers, 15(9), Article ID 2437.
Open this publication in new window or tab >>Investigating microRNA Profiles in Prostate Cancer Bone Metastases and Functional Effects of microRNA-23c and microRNA-4328
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2023 (English)In: Cancers, ISSN 2072-6694, Vol. 15, no 9, article id 2437Article in journal (Refereed) Published
Abstract [en]

MicroRNAs (miRNAs) are aberrantly expressed in prostate cancer (PC), but comprehensive knowledge about their levels and function in metastatic PC is lacking. Here, we explored the differential expression of miRNA profiles during PC progression to bone metastasis, and further focused on the downregulation of miRNA-23c and -4328 and their impact on PC growth in experimental models. Using microarray screening, the levels of 1510 miRNAs were compared between bone metastases (n = 14), localized PC (n = 7) and benign prostate tissue (n = 7). Differentially expressed miRNAs (n = 4 increased and n = 75 decreased, p < 0.05) were identified, of which miRNA-1, -23c, -143-3p, -143-5p, -145-3p, -205-5p, -221-3p, -222-3p and -4328 showed consistent downregulation during disease progression (benign > localized PC > bone metastases). The downregulation of miRNA-23c and -4328 was confirmed by reverse transcription and quantitative polymerase chain reaction analysis of 67 metastasis, 12 localized PC and 12 benign prostate tissue samples. The stable overexpression of miRNA-23c and -4328 in the 22Rv1 and PC-3 cell lines resulted in reduced PC cell growth in vitro, and in the secretion of high levels of miRNA-23c (but not -4328) in extracellular vesicles. However, no tumor suppressive effects were observed from miRNA-23c overexpression in PC-3 cells subcutaneously grown in mice. In conclusion, bone metastases display a profound reduction of miRNA levels compared to localized PC and benign disease. The downregulation of those miRNAs, including miRNA-23c and -4328, may lead to a loss of tumor suppressive effects and provide biomarker and therapeutic possibilities that deserve to be further explored.

Place, publisher, year, edition, pages
MDPI, 2023
Keywords
blood vessels, bone metastasis, extracellular vesicles, microarray, microRNA-23c, microRNA-4328, proliferation, prostate cancer, proteomics
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-209116 (URN)10.3390/cancers15092437 (DOI)000986796000001 ()2-s2.0-85159230526 (Scopus ID)
Funder
Swedish Research Council, 2022-00946Swedish Cancer Society, 21-1856Swedish Foundation for Strategic Research, RB13-0119Cancerforskningsfonden i Norrland, AMP 21-1061Prostatacancerförbundet
Available from: 2023-06-07 Created: 2023-06-07 Last updated: 2023-10-23Bibliographically approved
Schmidt, J. A., Huybrechts, I., Overvad, K., Eriksen, A. K., Tjønneland, A., Kaaks, R., . . . Perez-Cornago, A. (2023). Protein and amino acid intakes in relation to prostate cancer risk and mortality: A prospective study in the European Prospective Investigation into Cancer and Nutrition. Cancer Medicine, 12(4), 4725-4738
Open this publication in new window or tab >>Protein and amino acid intakes in relation to prostate cancer risk and mortality: A prospective study in the European Prospective Investigation into Cancer and Nutrition
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2023 (English)In: Cancer Medicine, E-ISSN 2045-7634, Vol. 12, no 4, p. 4725-4738Article in journal (Refereed) Published
Abstract [en]

Background: The association between protein intake and prostate cancer risk remains unclear.

Aims: To prospectively investigate the associations of dietary intakes of total protein, protein from different dietary sources, and amino acids with prostate cancer risk and mortality.

Methods: In 131,425 men from the European Prospective Investigation into Cancer and Nutrition, protein and amino acid intakes were estimated using validated dietary questionnaires. Multivariable-adjusted Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: During a mean follow-up of 14.2 years, 6939 men were diagnosed with prostate cancer and 914 died of the disease. Dairy protein was positively associated with overall prostate cancer risk in the three highest fifths compared to the lowest (HRQ3=1.14 (95% CI 1.05–1.23); HRQ4=1.09 (1.01–1.18); HRQ5=1.10 (1.02–1.19)); similar results were observed for yogurt protein (HRQ3=1.14 (1.05–1.24); HRQ4=1.09 (1.01–1.18); HRQ5=1.12 (1.04–1.21)). For egg protein intake and prostate cancer mortality, no association was observed by fifths, but there was suggestive evidence of a positive association in the analysis per standard deviation increment. There was no strong evidence of associations with different tumour subtypes.

Discussion: Considering the weak associations and many tests, the results must be interpreted with caution.

Conclusion: This study does not provide strong evidence for an association of intakes of total protein, protein from different dietary sources or amino acids with prostate cancer risk or mortality. However, our results may suggest some weak positive associations, which need to be confirmed in large-scale, pooled analyses of prospective data.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023
Keywords
dietary amino acid intakes, dietary protein intakes, prostate cancer incidence, prostate cancer mortality, tumour subtypes
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-200094 (URN)10.1002/cam4.5289 (DOI)000858927500001 ()36148781 (PubMedID)2-s2.0-85138609288 (Scopus ID)
Available from: 2022-10-13 Created: 2022-10-13 Last updated: 2024-01-17Bibliographically approved
Watts, E. L., Perez-Cornago, A., Fensom, G. K., Smith-Byrne, K., Noor, U., Andrews, C. D., . . . Travis, R. C. (2022). Circulating free testosterone and risk of aggressive prostate cancer: Prospective and Mendelian randomisation analyses in international consortia. International Journal of Cancer, 151(7), 1033-1046
Open this publication in new window or tab >>Circulating free testosterone and risk of aggressive prostate cancer: Prospective and Mendelian randomisation analyses in international consortia
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2022 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 151, no 7, p. 1033-1046Article in journal (Refereed) Published
Abstract [en]

Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone-binding globulin (SHBG) with aggressive, overall and early-onset prostate cancer. In blood-based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse-variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08-1.40). In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02-1.28; Phet =.0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08-1.34; blood-based: 1.03, 1.01-1.05) and early-onset prostate cancer (MR: 1.37, 1.09-1.73; blood-based: 1.08, 0.98-1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood-based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups.

Place, publisher, year, edition, pages
John Wiley & Sons, 2022
Keywords
aggressive prostate cancer, Mendelian randomisation, prostate cancer, SHBG, testosterone
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-198044 (URN)10.1002/ijc.34116 (DOI)000807068200001 ()35579976 (PubMedID)2-s2.0-85133539795 (Scopus ID)
Available from: 2022-07-15 Created: 2022-07-15 Last updated: 2023-05-23Bibliographically approved
Thysell, E., Köhn, L., Semenas, J., Järemo, H., Freyhult, E., Lundholm, M., . . . Wikström, P. (2022). Clinical and biological relevance of the transcriptomic-based prostate cancer metastasis subtypes MetA-C. Molecular Oncology (4)
Open this publication in new window or tab >>Clinical and biological relevance of the transcriptomic-based prostate cancer metastasis subtypes MetA-C
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2022 (English)In: Molecular Oncology, ISSN 1574-7891, E-ISSN 1878-0261, no 4Article in journal (Refereed) Published
Abstract [en]

To improve treatment of metastatic prostate cancer, the biology of metastases needs to be understood. We recently described three subtypes of prostate cancer bone metastases (MetA-C), based on differential gene expression. The aim of this study was to verify the clinical relevance of these subtypes, and to explore their biology and relations to genetic drivers. Freshly-frozen metastasis samples were obtained as hormone-naive (n=17), short-term castrated (n=21) or castration resistant (n=65) from a total of 67 patients. Previously published sequencing data from 573 metastasis samples was also analyzed. Through transcriptome profiling and sample classification based on a set of predefined MetA-C-differentiating genes, we found that most metastases were heterogeneous for the MetA-C subtypes. Overall, MetA was the most common subtype, while MetB was significantly enriched in castration-resistant samples and in liver metastases, and consistently associated with poor prognosis. By gene set enrichment analysis, the phenotype of MetA was described by high androgen response, protein secretion and adipogenesis, MetB by high cell cycle activity and DNA repair, and MetC by epithelial-to-mesenchymal transition and inflammation. The MetB subtype demonstrated single-nucleotide variants of RB transcriptional corepressor 1 (RB1) and loss of 21 genes at chromosome 13, including RB1, but provided independent prognostic value to those genetic aberrations. In conclusion, a distinct set of gene transcripts can be used to classify prostate cancer metastases into the subtypes MetA-C. The MetA-C subtypes show diverse biology, organ tropism and prognosis. The MetA-C classification may be used independently, or in combination with genetic markers, primarily to identify MetB patients in need of complementary therapy to conventional androgen-receptor-targeting treatments.

Place, publisher, year, edition, pages
John Wiley & Sons, 2022
Keywords
MetA-C, Metastasis, Prognosis, Prostate cancer, Subtypes, Transcriptomic
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-190463 (URN)10.1002/1878-0261.13158 (DOI)000734478400001 ()34889043 (PubMedID)2-s2.0-85121666619 (Scopus ID)
Available from: 2021-12-16 Created: 2021-12-16 Last updated: 2023-10-23Bibliographically approved
Wikström, P., Halin Bergström, S., Josefsson, A., Semenas, J., Nordstrand, A., Thysell, E., . . . Bergh, A. (2022). Epithelial and stromal characteristics of primary tumors predict the bone metastatic subtype of prostate cancer and patient survival after androgen-deprivation therapy. Cancers, 14(21), Article ID 5195.
Open this publication in new window or tab >>Epithelial and stromal characteristics of primary tumors predict the bone metastatic subtype of prostate cancer and patient survival after androgen-deprivation therapy
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2022 (English)In: Cancers, ISSN 2072-6694, Vol. 14, no 21, article id 5195Article in journal (Refereed) Published
Abstract [en]

Prostate cancer (PC) bone metastases can be divided into transcriptomic subtypes, by us termed MetA-C. The MetB subtype, constituting about 20% of the cases, is characterized by high cell cycle activity, low androgen receptor (AR) activity, and a limited response to standard androgen deprivation therapy (ADT). Complementary treatments should preferably be introduced early on if the risk of developing metastases of the MetB subtype is predicted to behigh. In this study, we therefore examined if the bone metastatic subtype and patient outcome after ADT could be predicted by immunohistochemical analysis of epithelial and stromal cell markers in primary tumor biopsies obtained at diagnosis (n = 98). In this advanced patient group, primary tumor International Society of Urological Pathology (ISUP) grade was not associated with outcome or metastasis subtype. In contrast, high tumor cell Ki67 labeling (proliferation) in combination with low tumor cell immunoreactivity for PSA, and a low fraction of AR positive stroma cells in the primary tumors were prognostic for poor survival after ADT. Accordingly, the same tissue markers were associated with developing metastases enriched for the aggressive MetB subtype. The development of the contrasting MetA subtype, showing the best response to ADT, could be predicted by the opposite staining pattern. We conclude that outcome after ADT and metastasis subtype can, at least to some extent, be predicted by analysis of primary tumor characteristics, such as tumor cell proliferation and PSA expression, and AR expression in stromal cells.

Place, publisher, year, edition, pages
MDPI, 2022
Keywords
androgen receptor, bone metastases, ERG, Ki67, metastatic subtypes, PDGFRB, prostate cancer, PSA, SDF1, smooth muscle actin
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-201227 (URN)10.3390/cancers14215195 (DOI)000880962300001 ()36358614 (PubMedID)2-s2.0-85141664487 (Scopus ID)
Funder
Swedish Foundation for Strategic Research, RB13-0119Swedish Cancer Society, 19 0053Swedish Cancer Society, 19 0054Swedish Cancer Society, 21 1856Knut and Alice Wallenberg Foundation, KAW 2015.0114Swedish Research Council, 2018-02594Cancerforskningsfonden i Norrland, 22-2302Cancerforskningsfonden i Norrland, 21-2258
Available from: 2022-12-05 Created: 2022-12-05 Last updated: 2022-12-05Bibliographically approved
Östman, J. R., Pinto, R. C., Ebbels, T. M. D., Thysell, E., Hallmans, G. & Moazzami, A. A. (2022). Identification of prediagnostic metabolites associated with prostate cancer risk by untargeted mass spectrometry-based metabolomics: a case-control study nested in the Northern Sweden Health and Disease Study. International Journal of Cancer, 151(12), 2115-2127
Open this publication in new window or tab >>Identification of prediagnostic metabolites associated with prostate cancer risk by untargeted mass spectrometry-based metabolomics: a case-control study nested in the Northern Sweden Health and Disease Study
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2022 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 151, no 12, p. 2115-2127Article in journal (Refereed) Published
Abstract [en]

Prostate cancer (PCa) is the most common cancer form in males in many European and American countries, but there are still open questions regarding its etiology. Untargeted metabolomics can produce an unbiased global metabolic profile, with the opportunity for uncovering new plasma metabolites prospectively associated with risk of PCa, providing insights into disease etiology. We conducted a prospective untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics analysis using prediagnostic fasting plasma samples from 752 PCa case-control pairs nested within the Northern Sweden Health and Disease Study (NSHDS). The pairs were matched by age, BMI, and sample storage time. Discriminating features were identified by a combination of orthogonal projection to latent structures-effect projections (OPLS-EP) and Wilcoxon signed-rank tests. Their prospective associations with PCa risk were investigated by conditional logistic regression. Subgroup analyses based on stratification by disease aggressiveness and baseline age were also conducted. Various free fatty acids and phospholipids were positively associated with overall risk of PCa and in various stratification subgroups. Aromatic amino acids were positively associated with overall risk of PCa. Uric acid was positively, and glucose negatively, associated with risk of PCa in the older subgroup. This is the largest untargeted LC-MS based metabolomics study to date on plasma metabolites prospectively associated with risk of developing PCa. Different subgroups of disease aggressiveness and baseline age showed different associations with metabolites. The findings suggest that shifts in plasma concentrations of metabolites in lipid, aromatic amino acid, and glucose metabolism are associated with risk of developing PCa during the following two decades.

Place, publisher, year, edition, pages
John Wiley & Sons, 2022
Keywords
liquid chromatography-mass spectrometry, nested case-control study, prostate cancer, risk biomarkers, untargeted metabolomics
National Category
Cancer and Oncology Nutrition and Dietetics
Research subject
Oncology
Identifiers
urn:nbn:se:umu:diva-198934 (URN)10.1002/ijc.34223 (DOI)000839504600001 ()35866293 (PubMedID)2-s2.0-85135769811 (Scopus ID)
Funder
Science for Life Laboratory, SciLifeLabSwedish Research Council, 2017-00650Swedish Research Council, 222-2014-1341
Available from: 2022-09-16 Created: 2022-09-16 Last updated: 2023-05-23Bibliographically approved
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