Association of Prediagnostic Blood Metabolomics with Prostate Cancer Defined by ERG or PTEN Molecular Subtypes
BACKGROUND: The TMPRSS2:ERG gene fusion and PTEN loss are two of the most common somatic molecular alterations in prostate cancer. Here, we investigated the association of prediagnostic-circulating metabolomics and prostate cancer defined by ERG or PTEN status to improve understanding of these etiol...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Association for Cancer Research (AACR)
2021
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| Online Access: | https://hdl.handle.net/1721.1/138495 |
| _version_ | 1811093386541662208 |
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| author | Feng, Xiaoshuang Zhou, Cindy Ke Clish, Clary B Wilson, Kathryn M Pernar, Claire H Dickerman, Barbra A Loda, Massimo Finn, Stephen P Penney, Kathryn L Schmidt, Daniel R Heiden, Matthew G Vander Giovannucci, Edward L Ebot, Ericka M Mucci, Lorelei A |
| author_facet | Feng, Xiaoshuang Zhou, Cindy Ke Clish, Clary B Wilson, Kathryn M Pernar, Claire H Dickerman, Barbra A Loda, Massimo Finn, Stephen P Penney, Kathryn L Schmidt, Daniel R Heiden, Matthew G Vander Giovannucci, Edward L Ebot, Ericka M Mucci, Lorelei A |
| author_sort | Feng, Xiaoshuang |
| collection | MIT |
| description | BACKGROUND: The TMPRSS2:ERG gene fusion and PTEN loss are two of the most common somatic molecular alterations in prostate cancer. Here, we investigated the association of prediagnostic-circulating metabolomics and prostate cancer defined by ERG or PTEN status to improve understanding of these etiologically distinct molecular prostate cancer subtypes. METHODS: The study was performed among 277 prostate cancer cases with ERG status, 211 with PTEN status, and 294 controls nested in the Health Professionals Follow-up Study (HPFS) and the Physicians' Health Study (PHS). We profiled 223 polar and non-polar metabolites using LC-MS in prediagnostic plasma specimens. We applied enrichment analysis and multinomial logistic regression models to identify biological metabolite classes and individual metabolites associated with prostate cancer defined by ERG or PTEN status. RESULTS: Compared with noncancer controls, sphingomyelin (P: 0.01), ceramide (P: 0.04), and phosphatidylethanolamine (P: 0.03) circulating levels were enriched among ERG-positive prostate cancer cases. Sphingomyelins (P: 0.02), ceramides (P: 0.005), and amino acids (P: 0.02) were enriched among tumors exhibiting PTEN-loss; unsaturated diacylglycerols (P: 0.003) were enriched among PTEN-intact cases; and unsaturated triacylglycerols were enriched among both PTEN-loss (P: 0.001) and PTEN-intact (P: 0.0001) cases. Although several individual metabolites identified in the above categories were nominally associated with ERG or PTEN-defined prostate cancer, none remained significant after accounting for multiple testing. CONCLUSIONS: The molecular process of prostate carcinogenesis may be distinct for men with different metabolomic profiles. IMPACT: These novel findings provide insights into the metabolic environment for the development of prostate cancer. |
| first_indexed | 2024-09-23T15:44:26Z |
| format | Article |
| id | mit-1721.1/138495 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T15:44:26Z |
| publishDate | 2021 |
| publisher | American Association for Cancer Research (AACR) |
| record_format | dspace |
| spelling | mit-1721.1/1384952021-12-17T03:04:09Z Association of Prediagnostic Blood Metabolomics with Prostate Cancer Defined by ERG or PTEN Molecular Subtypes Feng, Xiaoshuang Zhou, Cindy Ke Clish, Clary B Wilson, Kathryn M Pernar, Claire H Dickerman, Barbra A Loda, Massimo Finn, Stephen P Penney, Kathryn L Schmidt, Daniel R Heiden, Matthew G Vander Giovannucci, Edward L Ebot, Ericka M Mucci, Lorelei A BACKGROUND: The TMPRSS2:ERG gene fusion and PTEN loss are two of the most common somatic molecular alterations in prostate cancer. Here, we investigated the association of prediagnostic-circulating metabolomics and prostate cancer defined by ERG or PTEN status to improve understanding of these etiologically distinct molecular prostate cancer subtypes. METHODS: The study was performed among 277 prostate cancer cases with ERG status, 211 with PTEN status, and 294 controls nested in the Health Professionals Follow-up Study (HPFS) and the Physicians' Health Study (PHS). We profiled 223 polar and non-polar metabolites using LC-MS in prediagnostic plasma specimens. We applied enrichment analysis and multinomial logistic regression models to identify biological metabolite classes and individual metabolites associated with prostate cancer defined by ERG or PTEN status. RESULTS: Compared with noncancer controls, sphingomyelin (P: 0.01), ceramide (P: 0.04), and phosphatidylethanolamine (P: 0.03) circulating levels were enriched among ERG-positive prostate cancer cases. Sphingomyelins (P: 0.02), ceramides (P: 0.005), and amino acids (P: 0.02) were enriched among tumors exhibiting PTEN-loss; unsaturated diacylglycerols (P: 0.003) were enriched among PTEN-intact cases; and unsaturated triacylglycerols were enriched among both PTEN-loss (P: 0.001) and PTEN-intact (P: 0.0001) cases. Although several individual metabolites identified in the above categories were nominally associated with ERG or PTEN-defined prostate cancer, none remained significant after accounting for multiple testing. CONCLUSIONS: The molecular process of prostate carcinogenesis may be distinct for men with different metabolomic profiles. IMPACT: These novel findings provide insights into the metabolic environment for the development of prostate cancer. 2021-12-16T13:26:42Z 2021-12-16T13:26:42Z 2021 2021-12-16T13:23:46Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/138495 Feng, Xiaoshuang, Zhou, Cindy Ke, Clish, Clary B, Wilson, Kathryn M, Pernar, Claire H et al. 2021. "Association of Prediagnostic Blood Metabolomics with Prostate Cancer Defined by ERG or PTEN Molecular Subtypes." Cancer Epidemiology Biomarkers and Prevention, 30 (5). en 10.1158/1055-9965.EPI-20-1363 Cancer Epidemiology Biomarkers and Prevention Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for Cancer Research (AACR) PMC |
| spellingShingle | Feng, Xiaoshuang Zhou, Cindy Ke Clish, Clary B Wilson, Kathryn M Pernar, Claire H Dickerman, Barbra A Loda, Massimo Finn, Stephen P Penney, Kathryn L Schmidt, Daniel R Heiden, Matthew G Vander Giovannucci, Edward L Ebot, Ericka M Mucci, Lorelei A Association of Prediagnostic Blood Metabolomics with Prostate Cancer Defined by ERG or PTEN Molecular Subtypes |
| title | Association of Prediagnostic Blood Metabolomics with Prostate Cancer Defined by ERG or PTEN Molecular Subtypes |
| title_full | Association of Prediagnostic Blood Metabolomics with Prostate Cancer Defined by ERG or PTEN Molecular Subtypes |
| title_fullStr | Association of Prediagnostic Blood Metabolomics with Prostate Cancer Defined by ERG or PTEN Molecular Subtypes |
| title_full_unstemmed | Association of Prediagnostic Blood Metabolomics with Prostate Cancer Defined by ERG or PTEN Molecular Subtypes |
| title_short | Association of Prediagnostic Blood Metabolomics with Prostate Cancer Defined by ERG or PTEN Molecular Subtypes |
| title_sort | association of prediagnostic blood metabolomics with prostate cancer defined by erg or pten molecular subtypes |
| url | https://hdl.handle.net/1721.1/138495 |
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