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      Androgen deficiency is associated with a better prognosis in glioblastoma

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          Abstract

          Background

          The androgen receptor (AR) has been demonstrated to play a role in the pathogenesis of glioblastoma; however, the implications of circulating testosterone levels in the biology of glioblastoma remain unknown.

          Aim

          This study aimed to analyze the association between circulating testosterone levels and the prognosis of patients with glioblastoma.

          Methods

          Forty patients with primary glioblastoma were included in the study. The main prognostic endpoint was progression-free survival (PFS). Circulating testosterone levels were used to determine the state of androgen deficiency (AD). AR expression was analyzed by reverse-transcriptase polymerase chain reaction, Western blot, and immunofluorescence. Survival analysis was performed using the log-rank test and univariate and multivariate Cox regression analysis.

          Results

          Most of the patients showed AR expression, and it was mainly located in the cytoplasm, as well as in the nucleus of tumor cells. Patients with AD presented a better PFS than those patients with normal levels (252.0 vs. 135.0 days; p = 0.041). Furthermore, normal androgenic status was an independent risk factor for progression in a multivariate regression model (hazard ratio = 6.346; p = 0.004).

          Conclusion

          Circulating testosterone levels are associated with the prognosis of glioblastoma because patients with AD show a better prognosis than those with normal androgenic status.

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          Most cited references38

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          Analyzing real-time PCR data by the comparative CT method

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            The Molecular Taxonomy of Primary Prostate Cancer.

            (2015)
            There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects.
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              Primary brain tumours in adults

              Primary CNS tumours refer to a heterogeneous group of tumours arising from cells within the CNS, and can be benign or malignant. Malignant primary brain tumours remain among the most difficult cancers to treat, with a 5 year overall survival no greater than 35%. The most common malignant primary brain tumours in adults are gliomas. Recent advances in molecular biology have improved understanding of glioma pathogenesis, and several clinically significant genetic alterations have been described. A number of these (IDH, 1p/19q codeletion, H3 Lys27Met, and RELA-fusion) are now combined with histology in the revised 2016 WHO classification of CNS tumours. It is likely that understanding such molecular alterations will contribute to the diagnosis, grading, and treatment of brain tumours. This progress in genomics, along with significant advances in cancer and CNS immunology, has defined a new era in neuro-oncology and holds promise for diagntic and therapeutic improvement. The challenge at present is to translate these advances into effective treatments. Current efforts are focused on developing molecular targeted therapies, immunotherapies, gene therapies, and novel drug-delivery technologies. Results with single-agent therapies have been disappointing so far, and combination therapies seem to be required to achieve a broad and durable antitumour response. Biomarker-targeted clinical trials could improve efficiencies of therapeutic development.
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                Author and article information

                Contributors
                jplabel@gobiernodecanarias.org
                Journal
                Eur J Med Res
                Eur J Med Res
                European Journal of Medical Research
                BioMed Central (London )
                0949-2321
                2047-783X
                17 January 2024
                17 January 2024
                2024
                : 29
                : 57
                Affiliations
                [1 ]Neurosurgery Department, Hospital Universitario de Canarias, ( https://ror.org/05qndj312) Calle Ofra s/n La Cuesta, CP 38320 La Laguna, S/C de Tenerife Spain
                [2 ]Molecular Biology Department, University of La Laguna, ( https://ror.org/01r9z8p25) La Laguna, Spain
                [3 ]Biochemistry Laboratory, Hospital Universitario de Canarias, ( https://ror.org/05qndj312) La Laguna, Spain
                Article
                1648
                10.1186/s40001-024-01648-3
                10792837
                38233838
                1031d1d0-d537-4b21-80ca-b780ac5cc1ac
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 11 May 2023
                : 7 January 2024
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100023554, Fundación Canaria Instituto de Investigación Sanitaria de Canarias;
                Award ID: PIFIISC19/31
                Categories
                Research
                Custom metadata
                © BioMed Central Ltd., part of Springer Nature 2024

                Medicine
                glioblastoma,testosterone,androgen receptor,prognosis
                Medicine
                glioblastoma, testosterone, androgen receptor, prognosis

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