Genome‐wide methylation profiling of diagnostic tumor specimens identified DNA methylation markers associated with metastasis among men with untreated localized prostate cancer
Abstract Background We used a genome‐wide discovery approach to identify methylation markers associated with metastasis in men with localized prostate cancer (PCa), as better identification of those at high risk of metastasis can inform treatment decision‐making. Methods We identified men with local...
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| Format: | Article |
| Language: | English |
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Wiley
2023-09-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.6507 |
| _version_ | 1827386797826506752 |
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| author | Chun R. Chao Jeff Slezak Kimberly Siegmund Kimberly Cannavale Yu‐Hsiang Shu Gary W. Chien Xu‐Feng Chen Feng Shi Nan Song Stephen K. Van Den Eeden Jiaoti Huang |
| author_facet | Chun R. Chao Jeff Slezak Kimberly Siegmund Kimberly Cannavale Yu‐Hsiang Shu Gary W. Chien Xu‐Feng Chen Feng Shi Nan Song Stephen K. Van Den Eeden Jiaoti Huang |
| author_sort | Chun R. Chao |
| collection | DOAJ |
| description | Abstract Background We used a genome‐wide discovery approach to identify methylation markers associated with metastasis in men with localized prostate cancer (PCa), as better identification of those at high risk of metastasis can inform treatment decision‐making. Methods We identified men with localized PCa at Kaiser Permanente California (January 1, 1997–December 31, 2006) who did not receive curative treatment and followed them for 10 years to determine metastasis status. Cases were chart review‐confirmed metastasis, and controls were matched using density sampling. We extracted DNA from the cancerous areas in the archived diagnostic tissue blocks. We used Illumina's Infinium MethylationEPIC BeadChip for methylation interrogation. We used conditional logistic regression and Bonferroni's correction to identify methylation markers associated with metastasis. In a separate validation cohort (2007), we evaluated the added predictive utility of the methylation score beyond clinical risk score. Results Among 215 cases and 404 controls, 31 CpG sites were significantly associated with metastasis status. Adding the methylation score to the clinical risk score did not meaningfully improve the c‐statistic (0.80–0.81) in the validation cohort, though the score itself was statistically significant (p < 0.01). In the validation cohort, both clinical risk score alone and methylation marker score alone are well calibrated for predicted 10‐year metastasis risks. Adding the methylation score to the clinical risk score only marginally improved predictive risk calibration. Conclusion Our findings do not support the use of these markers to improve clinical risk prediction. The methylation markers identified may inform novel hypothesis in the roles of these genetic regions in metastasis development. |
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| format | Article |
| id | doaj.art-7e2cb60011cb4623851ef31c8c7570c4 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-03-08T15:51:47Z |
| publishDate | 2023-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-7e2cb60011cb4623851ef31c8c7570c42024-01-09T05:21:15ZengWileyCancer Medicine2045-76342023-09-011218188371884910.1002/cam4.6507Genome‐wide methylation profiling of diagnostic tumor specimens identified DNA methylation markers associated with metastasis among men with untreated localized prostate cancerChun R. Chao0Jeff Slezak1Kimberly Siegmund2Kimberly Cannavale3Yu‐Hsiang Shu4Gary W. Chien5Xu‐Feng Chen6Feng Shi7Nan Song8Stephen K. Van Den Eeden9Jiaoti Huang10Department of Research and Evaluation Kaiser Permanente Southern California Pasadena California USADepartment of Research and Evaluation Kaiser Permanente Southern California Pasadena California USADepartment of Population and Public Health Sciences, USC Keck School of Medicine University of Southern California Los Angeles California USADepartment of Research and Evaluation Kaiser Permanente Southern California Pasadena California USADepartment of Research and Evaluation Kaiser Permanente Southern California Pasadena California USADepartment of Urology, Los Angeles Medical Center Kaiser Permanente Southern California Los Angeles California USADepartment of Pathology, School of Medicine Duke University Durham North Carolina USADepartment of Pathology, Beijing Shijitan Hospital Capital Medical University Beijing ChinaDepartment of Urology Beijing Shijitan Hospital Capital Medical University Beijing ChinaDivision of Research Kaiser Permanente Northern California Oakland California USADepartment of Pathology, School of Medicine Duke University Durham North Carolina USAAbstract Background We used a genome‐wide discovery approach to identify methylation markers associated with metastasis in men with localized prostate cancer (PCa), as better identification of those at high risk of metastasis can inform treatment decision‐making. Methods We identified men with localized PCa at Kaiser Permanente California (January 1, 1997–December 31, 2006) who did not receive curative treatment and followed them for 10 years to determine metastasis status. Cases were chart review‐confirmed metastasis, and controls were matched using density sampling. We extracted DNA from the cancerous areas in the archived diagnostic tissue blocks. We used Illumina's Infinium MethylationEPIC BeadChip for methylation interrogation. We used conditional logistic regression and Bonferroni's correction to identify methylation markers associated with metastasis. In a separate validation cohort (2007), we evaluated the added predictive utility of the methylation score beyond clinical risk score. Results Among 215 cases and 404 controls, 31 CpG sites were significantly associated with metastasis status. Adding the methylation score to the clinical risk score did not meaningfully improve the c‐statistic (0.80–0.81) in the validation cohort, though the score itself was statistically significant (p < 0.01). In the validation cohort, both clinical risk score alone and methylation marker score alone are well calibrated for predicted 10‐year metastasis risks. Adding the methylation score to the clinical risk score only marginally improved predictive risk calibration. Conclusion Our findings do not support the use of these markers to improve clinical risk prediction. The methylation markers identified may inform novel hypothesis in the roles of these genetic regions in metastasis development.https://doi.org/10.1002/cam4.6507epigeneticsmetastasismethylationprostate cancerrisk model |
| spellingShingle | Chun R. Chao Jeff Slezak Kimberly Siegmund Kimberly Cannavale Yu‐Hsiang Shu Gary W. Chien Xu‐Feng Chen Feng Shi Nan Song Stephen K. Van Den Eeden Jiaoti Huang Genome‐wide methylation profiling of diagnostic tumor specimens identified DNA methylation markers associated with metastasis among men with untreated localized prostate cancer Cancer Medicine epigenetics metastasis methylation prostate cancer risk model |
| title | Genome‐wide methylation profiling of diagnostic tumor specimens identified DNA methylation markers associated with metastasis among men with untreated localized prostate cancer |
| title_full | Genome‐wide methylation profiling of diagnostic tumor specimens identified DNA methylation markers associated with metastasis among men with untreated localized prostate cancer |
| title_fullStr | Genome‐wide methylation profiling of diagnostic tumor specimens identified DNA methylation markers associated with metastasis among men with untreated localized prostate cancer |
| title_full_unstemmed | Genome‐wide methylation profiling of diagnostic tumor specimens identified DNA methylation markers associated with metastasis among men with untreated localized prostate cancer |
| title_short | Genome‐wide methylation profiling of diagnostic tumor specimens identified DNA methylation markers associated with metastasis among men with untreated localized prostate cancer |
| title_sort | genome wide methylation profiling of diagnostic tumor specimens identified dna methylation markers associated with metastasis among men with untreated localized prostate cancer |
| topic | epigenetics metastasis methylation prostate cancer risk model |
| url | https://doi.org/10.1002/cam4.6507 |
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