{"title":"厌食症肺癌患者基因表达调控的DNA甲基化特征","authors":"Alessio Molfino, Francesca Ambrosani, Silvia Udali, Giovanni Imbimbo, Sara Moruzzi, Annalisa Castagna, Patrizia Pattini, Federica Tambaro, Cesarina Ramaccini, Maurizio Muscaritoli, Simonetta Friso","doi":"10.3390/nu16213721","DOIUrl":null,"url":null,"abstract":"<p><strong>Background/objectives: </strong>The pathophysiology of cancer anorexia is multifactorial and unclear. Transcriptomic analysis from PBMCs RNA showed diverse patterns of gene expression pathways in anorexic cancer patients. We assessed whether the different transcriptomic signatures are modulated by DNA methylation in lung cancer patients presenting with poor appetite.</p><p><strong>Methods: </strong>Lung cancer patients and controls were enrolled, and anorexia was assessed by the FAACT-score questionnaire. Genome-wide DNA methylation was determined by Human Infinium MethylationEPIC BeadChip Kit. Data from genome-wide methylation analysis were merged with those from gene expression analysis, previously obtained by RNA sequencing (NGS). Four groups of genes were identified for each comparison: hypermethylated repressed, hypermethylated induced, hypomethylated repressed, and hypomethylated induced.</p><p><strong>Results: </strong>Cancer patients (<i>n</i> = 16) showed 382 differentially methylated genes when compared with controls (<i>n</i> = 8). Anorexic patients (<i>n</i> = 8) presented 586 hypomethylated and 174 hypermethylated genes compared with controls. In anorexic patients vs. non-anorexic (<i>n</i> = 8), 211 genes were identified as hypomethylated and 90 hypermethylated. When microarray methylation data were merged with transcriptomic data by RNA sequencing, we observed significant differences in anorexic patients vs. controls; a total of 42 genes resulted as hypomethylated and induced, 5 hypermethylated repressed, 10 hypermethylated induced, and 15 hypomethylated repressed. The CG sites analyzed by targeted bisulfite NGS in four genes of interest (FLNA, PGRMC1, GNL3L, and FHL1) resulting as hypomethylated in anorexic vs. controls allowed the validation of the data obtained from DNA methylation. Interestingly, the four genes resulted as hypomethylated in anorexic patients vs. non-anorexic patients and vs. controls (<i>p</i> < 0.0001).</p><p><strong>Conclusions: </strong>Our data support that methylation is implicated in cancer-associated anorexia and nutritional derangements among lung cancer patients.</p>","PeriodicalId":19486,"journal":{"name":"Nutrients","volume":"16 21","pages":""},"PeriodicalIF":4.8000,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11547925/pdf/","citationCount":"0","resultStr":"{\"title\":\"DNA Methylation Signatures Characterize Gene Expression Modulation in Lung Cancer Patients Affected by Anorexia.\",\"authors\":\"Alessio Molfino, Francesca Ambrosani, Silvia Udali, Giovanni Imbimbo, Sara Moruzzi, Annalisa Castagna, Patrizia Pattini, Federica Tambaro, Cesarina Ramaccini, Maurizio Muscaritoli, Simonetta Friso\",\"doi\":\"10.3390/nu16213721\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background/objectives: </strong>The pathophysiology of cancer anorexia is multifactorial and unclear. Transcriptomic analysis from PBMCs RNA showed diverse patterns of gene expression pathways in anorexic cancer patients. We assessed whether the different transcriptomic signatures are modulated by DNA methylation in lung cancer patients presenting with poor appetite.</p><p><strong>Methods: </strong>Lung cancer patients and controls were enrolled, and anorexia was assessed by the FAACT-score questionnaire. Genome-wide DNA methylation was determined by Human Infinium MethylationEPIC BeadChip Kit. Data from genome-wide methylation analysis were merged with those from gene expression analysis, previously obtained by RNA sequencing (NGS). Four groups of genes were identified for each comparison: hypermethylated repressed, hypermethylated induced, hypomethylated repressed, and hypomethylated induced.</p><p><strong>Results: </strong>Cancer patients (<i>n</i> = 16) showed 382 differentially methylated genes when compared with controls (<i>n</i> = 8). Anorexic patients (<i>n</i> = 8) presented 586 hypomethylated and 174 hypermethylated genes compared with controls. In anorexic patients vs. non-anorexic (<i>n</i> = 8), 211 genes were identified as hypomethylated and 90 hypermethylated. When microarray methylation data were merged with transcriptomic data by RNA sequencing, we observed significant differences in anorexic patients vs. controls; a total of 42 genes resulted as hypomethylated and induced, 5 hypermethylated repressed, 10 hypermethylated induced, and 15 hypomethylated repressed. The CG sites analyzed by targeted bisulfite NGS in four genes of interest (FLNA, PGRMC1, GNL3L, and FHL1) resulting as hypomethylated in anorexic vs. controls allowed the validation of the data obtained from DNA methylation. Interestingly, the four genes resulted as hypomethylated in anorexic patients vs. non-anorexic patients and vs. controls (<i>p</i> < 0.0001).</p><p><strong>Conclusions: </strong>Our data support that methylation is implicated in cancer-associated anorexia and nutritional derangements among lung cancer patients.</p>\",\"PeriodicalId\":19486,\"journal\":{\"name\":\"Nutrients\",\"volume\":\"16 21\",\"pages\":\"\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2024-10-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11547925/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nutrients\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3390/nu16213721\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NUTRITION & DIETETICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nutrients","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/nu16213721","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
DNA Methylation Signatures Characterize Gene Expression Modulation in Lung Cancer Patients Affected by Anorexia.
Background/objectives: The pathophysiology of cancer anorexia is multifactorial and unclear. Transcriptomic analysis from PBMCs RNA showed diverse patterns of gene expression pathways in anorexic cancer patients. We assessed whether the different transcriptomic signatures are modulated by DNA methylation in lung cancer patients presenting with poor appetite.
Methods: Lung cancer patients and controls were enrolled, and anorexia was assessed by the FAACT-score questionnaire. Genome-wide DNA methylation was determined by Human Infinium MethylationEPIC BeadChip Kit. Data from genome-wide methylation analysis were merged with those from gene expression analysis, previously obtained by RNA sequencing (NGS). Four groups of genes were identified for each comparison: hypermethylated repressed, hypermethylated induced, hypomethylated repressed, and hypomethylated induced.
Results: Cancer patients (n = 16) showed 382 differentially methylated genes when compared with controls (n = 8). Anorexic patients (n = 8) presented 586 hypomethylated and 174 hypermethylated genes compared with controls. In anorexic patients vs. non-anorexic (n = 8), 211 genes were identified as hypomethylated and 90 hypermethylated. When microarray methylation data were merged with transcriptomic data by RNA sequencing, we observed significant differences in anorexic patients vs. controls; a total of 42 genes resulted as hypomethylated and induced, 5 hypermethylated repressed, 10 hypermethylated induced, and 15 hypomethylated repressed. The CG sites analyzed by targeted bisulfite NGS in four genes of interest (FLNA, PGRMC1, GNL3L, and FHL1) resulting as hypomethylated in anorexic vs. controls allowed the validation of the data obtained from DNA methylation. Interestingly, the four genes resulted as hypomethylated in anorexic patients vs. non-anorexic patients and vs. controls (p < 0.0001).
Conclusions: Our data support that methylation is implicated in cancer-associated anorexia and nutritional derangements among lung cancer patients.
期刊介绍：
Nutrients (ISSN 2072-6643) is an international, peer-reviewed open access advanced forum for studies related to Human Nutrition. It publishes reviews, regular research papers and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
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