Alterations to DNA methylation patterns induced by chemotherapy treatment are associated with negative impacts on the olfactory pathway
Abstract 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,...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Breast Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13058-023-01730-4 |
| _version_ | 1797629863919616000 |
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| author | Peh Joo Ho Alexis Jiaying Khng Benita Kiat-Tee Tan Geok Hoon Lim Su-Ming Tan Veronique Kiak Mien Tan Ryan Shea Ying Cong Tan Elaine Hsuen Lim Philip Tsau-Choong Iau Ying Jia Chew Yi Ying Lim Mikael Hartman Ern Yu Tan Jingmei Li |
| author_facet | Peh Joo Ho Alexis Jiaying Khng Benita Kiat-Tee Tan Geok Hoon Lim Su-Ming Tan Veronique Kiak Mien Tan Ryan Shea Ying Cong Tan Elaine Hsuen Lim Philip Tsau-Choong Iau Ying Jia Chew Yi Ying Lim Mikael Hartman Ern Yu Tan Jingmei Li |
| author_sort | Peh Joo Ho |
| collection | DOAJ |
| description | Abstract 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 | 2024-03-11T10:59:47Z |
| format | Article |
| id | doaj.art-08fa501a0a194a4dbf1009ccbbf6f46f |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-03-11T10:59:47Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj.art-08fa501a0a194a4dbf1009ccbbf6f46f2023-11-12T12:34:22ZengBMCBreast Cancer Research1465-542X2023-11-0125111210.1186/s13058-023-01730-4Alterations to DNA methylation patterns induced by chemotherapy treatment are associated with negative impacts on the olfactory pathwayPeh Joo Ho0Alexis Jiaying Khng1Benita Kiat-Tee Tan2Geok Hoon Lim3Su-Ming Tan4Veronique Kiak Mien Tan5Ryan Shea Ying Cong Tan6Elaine Hsuen Lim7Philip Tsau-Choong Iau8Ying Jia Chew9Yi Ying Lim10Mikael Hartman11Ern Yu Tan12Jingmei Li13Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR)Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR)Department of Breast Surgery, Singapore General HospitalKK Breast Department, KK Women’s and Children’s HospitalDivision of Breast Surgery, Changi General HospitalDepartment of Breast Surgery, Singapore General HospitalDivision of Medical Oncology, National Cancer Centre SingaporeDivision of Medical Oncology, National Cancer Centre SingaporeDepartment of Surgery, University Surgical Cluster, National University Health SystemDepartment of Surgery, University Surgical Cluster, National University Health SystemSaw Swee Hock School of Public Health, National University of Singapore and National University Health SystemSaw Swee Hock School of Public Health, National University of Singapore and National University Health SystemDepartment of General Surgery, Tan Tock Seng HospitalGenome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR)Abstract 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.https://doi.org/10.1186/s13058-023-01730-4Epigenetic modificationBreast cancerTreatment responseDNA methylation |
| spellingShingle | Peh Joo Ho Alexis Jiaying Khng Benita Kiat-Tee Tan Geok Hoon Lim Su-Ming Tan Veronique Kiak Mien Tan Ryan Shea Ying Cong Tan Elaine Hsuen Lim Philip Tsau-Choong Iau Ying Jia Chew Yi Ying Lim Mikael Hartman Ern Yu Tan Jingmei Li Alterations to DNA methylation patterns induced by chemotherapy treatment are associated with negative impacts on the olfactory pathway Breast Cancer Research Epigenetic modification Breast cancer Treatment response DNA methylation |
| 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 | Epigenetic modification Breast cancer Treatment response DNA methylation |
| url | https://doi.org/10.1186/s13058-023-01730-4 |
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