Alterations to DNA methylation patterns induced by chemotherapy treatment are associated with negative impacts on the olfactory pathway
Background: Exposure to cytotoxic chemotherapy treatment may alter DNA methylation (DNAm) in breast cancer patients. Methods: We performed DNAm analysis in 125 breast cancer patients with blood drawn before and after chemotherapy, using the Illumina MethylationEPIC array. DNAm changes of 588,798 ind...
| Main Authors: | , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2024
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| Online Access: | https://hdl.handle.net/10356/173869 |
| _version_ | 1826128591041069056 |
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| author | Ho, Peh Joo Khng, Alexis Jiaying Tan, Benita Kiat-Tee Lim, Geok Hoon Tan, Su-Ming Tan, Veronique Kiak Mien Tan, Ryan Shea Ying Cong Lim, Elaine Hsuen Iau, Philip Tsau-Choong Chew, Ying Jia Lim, Yi Ying Hartman, Mikael Tan, Ern Yu Li, Jingmei |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Ho, Peh Joo Khng, Alexis Jiaying Tan, Benita Kiat-Tee Lim, Geok Hoon Tan, Su-Ming Tan, Veronique Kiak Mien Tan, Ryan Shea Ying Cong Lim, Elaine Hsuen Iau, Philip Tsau-Choong Chew, Ying Jia Lim, Yi Ying Hartman, Mikael Tan, Ern Yu Li, Jingmei |
| author_sort | Ho, Peh Joo |
| collection | NTU |
| description | Background: Exposure to cytotoxic chemotherapy treatment may alter DNA methylation (DNAm) in breast cancer patients. Methods: We performed DNAm analysis in 125 breast cancer patients with blood drawn before and after chemotherapy, using the Illumina MethylationEPIC array. DNAm changes of 588,798 individual CpGs (including 41,207 promoter regions) were evaluated using linear regression models adjusted for monocyte proportion. Gene set enrichment analyses (GSEA) were conducted to identify key Gene Ontology (GO) biological processes or Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with chemotherapy. Results were validated in a separate cohort of breast cancer patients who were treated (n = 1273) and not treated (n = 872) by chemotherapy (1808 blood, 337 saliva). Results: A total of 141 differentially methylated CpGs and 11 promoters were significantly associated with chemotherapy after multiple testing corrections in both the paired sample and single time point analyses. GSEA of promoter regions (pre-ranked by test statistics) identified six suppressed biological processes (p < 4.67e−8) related to sensory perception and detection of chemical stimuli, including smell perception (GO:0007606, GO:0007608, GO:0009593, GO:0050906, GO:0050907, and GO:0050911). The same six biological processes were significantly suppressed in the validation dataset (p < 9.02e−14). The KEGG pathway olfactory transduction (hsa04740) was also found to be significantly suppressed (p paired-samples = 1.72e−9, psingle-timepoint-blood = 2.03e−15 and p single-timepoint-saliva = 7.52e−56). Conclusion: The enrichment of imprinted genes within biological processes and pathways suggests a biological mechanism by which chemotherapy could affect the perception of smell. |
| first_indexed | 2024-10-01T07:27:26Z |
| format | Journal Article |
| id | ntu-10356/173869 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:27:26Z |
| publishDate | 2024 |
| record_format | dspace |
| spelling | ntu-10356/1738692024-03-10T15:38:00Z Alterations to DNA methylation patterns induced by chemotherapy treatment are associated with negative impacts on the olfactory pathway Ho, Peh Joo Khng, Alexis Jiaying Tan, Benita Kiat-Tee Lim, Geok Hoon Tan, Su-Ming Tan, Veronique Kiak Mien Tan, Ryan Shea Ying Cong Lim, Elaine Hsuen Iau, Philip Tsau-Choong Chew, Ying Jia Lim, Yi Ying Hartman, Mikael Tan, Ern Yu Li, Jingmei Lee Kong Chian School of Medicine (LKCMedicine) Tan Tock Seng Hospital Medicine, Health and Life Sciences Epigenetic modifcation Breast cancer Background: Exposure to cytotoxic chemotherapy treatment may alter DNA methylation (DNAm) in breast cancer patients. Methods: We performed DNAm analysis in 125 breast cancer patients with blood drawn before and after chemotherapy, using the Illumina MethylationEPIC array. DNAm changes of 588,798 individual CpGs (including 41,207 promoter regions) were evaluated using linear regression models adjusted for monocyte proportion. Gene set enrichment analyses (GSEA) were conducted to identify key Gene Ontology (GO) biological processes or Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with chemotherapy. Results were validated in a separate cohort of breast cancer patients who were treated (n = 1273) and not treated (n = 872) by chemotherapy (1808 blood, 337 saliva). Results: A total of 141 differentially methylated CpGs and 11 promoters were significantly associated with chemotherapy after multiple testing corrections in both the paired sample and single time point analyses. GSEA of promoter regions (pre-ranked by test statistics) identified six suppressed biological processes (p < 4.67e−8) related to sensory perception and detection of chemical stimuli, including smell perception (GO:0007606, GO:0007608, GO:0009593, GO:0050906, GO:0050907, and GO:0050911). The same six biological processes were significantly suppressed in the validation dataset (p < 9.02e−14). The KEGG pathway olfactory transduction (hsa04740) was also found to be significantly suppressed (p paired-samples = 1.72e−9, psingle-timepoint-blood = 2.03e−15 and p single-timepoint-saliva = 7.52e−56). Conclusion: The enrichment of imprinted genes within biological processes and pathways suggests a biological mechanism by which chemotherapy could affect the perception of smell. Agency for Science, Technology and Research (A*STAR) National Medical Research Council (NMRC) Published version This work was supported by the Agency for Science, Technology and Research (A*STAR), BMRC Central Research Fund (Applied Translational Research), NUS start-up Grant, National University Cancer Institute Singapore (NCIS) Centre Grant [NMRC/CG/NCIS/2010, NMRC/CG/012/2013, CGAug16M005, CG21APR1005], Breast Cancer Prevention Programme (BCPP), Asian Breast Cancer Research Fund, and the NMRC Clinician Scientist Award (SI Category) [NMRC/CSA-SI/0015/2017]. 2024-03-04T05:44:18Z 2024-03-04T05:44:18Z 2023 Journal Article Ho, P. J., Khng, A. J., Tan, B. K., Lim, G. H., Tan, S., Tan, V. K. M., Tan, R. S. Y. C., Lim, E. H., Iau, P. T., Chew, Y. J., Lim, Y. Y., Hartman, M., Tan, E. Y. & Li, J. (2023). Alterations to DNA methylation patterns induced by chemotherapy treatment are associated with negative impacts on the olfactory pathway. Breast Cancer Research, 25(1), 136-. https://dx.doi.org/10.1186/s13058-023-01730-4 1465-5411 https://hdl.handle.net/10356/173869 10.1186/s13058-023-01730-4 37932858 2-s2.0-85175816380 1 25 136 en NMRC/CG/NCIS/2010 NMRC/CG/012/2013 CGAug16M005 CG21APR1005 NMRC/CSA-SI/0015/2017 Breast Cancer Research © The Author(s) 2023. 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://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. application/pdf |
| spellingShingle | Medicine, Health and Life Sciences Epigenetic modifcation Breast cancer Ho, Peh Joo Khng, Alexis Jiaying Tan, Benita Kiat-Tee Lim, Geok Hoon Tan, Su-Ming Tan, Veronique Kiak Mien Tan, Ryan Shea Ying Cong Lim, Elaine Hsuen Iau, Philip Tsau-Choong Chew, Ying Jia Lim, Yi Ying Hartman, Mikael Tan, Ern Yu Li, Jingmei Alterations to DNA methylation patterns induced by chemotherapy treatment are associated with negative impacts on the olfactory pathway |
| title | Alterations to DNA methylation patterns induced by chemotherapy treatment are associated with negative impacts on the olfactory pathway |
| title_full | Alterations to DNA methylation patterns induced by chemotherapy treatment are associated with negative impacts on the olfactory pathway |
| title_fullStr | Alterations to DNA methylation patterns induced by chemotherapy treatment are associated with negative impacts on the olfactory pathway |
| title_full_unstemmed | Alterations to DNA methylation patterns induced by chemotherapy treatment are associated with negative impacts on the olfactory pathway |
| title_short | Alterations to DNA methylation patterns induced by chemotherapy treatment are associated with negative impacts on the olfactory pathway |
| title_sort | alterations to dna methylation patterns induced by chemotherapy treatment are associated with negative impacts on the olfactory pathway |
| topic | Medicine, Health and Life Sciences Epigenetic modifcation Breast cancer |
| url | https://hdl.handle.net/10356/173869 |
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