Genome-wide DNA methylation profiles in liver tissue at the precancerous stage and in hepatocellular carcinoma
| العنوان: | Genome-wide DNA methylation profiles in liver tissue at the precancerous stage and in hepatocellular carcinoma |
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| المؤلفون: | Setsuo Hirohashi, Tadashi Kondo, Sana Yokoi, Johji Inazawa, Eri Arai, Masahiro Gotoh, Hidenori Ojima, Saori Ushijima, Issei Imoto, Tatsuhiro Shibata, Tomoo Kosuge, Yae Kanai, Fumie Hosoda |
| المصدر: | International Journal of Cancer. 125:2854-2862 |
| بيانات النشر: | Wiley, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Male, Chromosomes, Artificial, Bacterial, Cancer Research, Pathology, medicine.medical_specialty, Carcinoma, Hepatocellular, Biology, medicine.disease_cause, Carcinoma, medicine, Humans, Genome, Human, Liver Neoplasms, DNA, Neoplasm, Methylation, DNA Methylation, Middle Aged, HCCS, Prognosis, medicine.disease, Molecular biology, Gene Expression Regulation, Neoplastic, Precancerous condition, Cell Transformation, Neoplastic, Liver, Oncology, CpG site, DNA methylation, CpG Islands, Female, Human genome, Neoplasm Recurrence, Local, Carcinogenesis, Precancerous Conditions, Genome-Wide Association Study |
| الوصف: | To clarify genome-wide DNA methylation profiles during hepatocarcinogenesis, bacterial artificial chromosome (BAC) array-based methylated CpG island amplification was performed on 126 tissue samples. The average numbers of BAC clones showing DNA hypo- or hypermethylation increased from noncancerous liver tissue obtained from patients with hepatocellular carcinomas (HCCs) (N) to HCCs. N appeared to be at the precancerous stage, showing DNA methylation alterations that were correlated with the future development of HCC. Using Wilcoxon test, 25 BAC clones, whose DNA methylation status was inherited by HCCs from N and were able to discriminate 15 N samples from 10 samples of normal liver tissue obtained from patients without HCCs (C) with 100% sensitivity and specificity, were identified. The criteria using the 25 BAC clones were able to discriminate 24 additional N samples from 26 C samples in the validation set with 95.8% sensitivity and 96.2% specificity. Using Wilcoxon test, 41 BAC clones, whose DNA methylation status was able to discriminate patients who survived more than 4 years after hepatectomy from patients who suffered recurrence within 6 months and died within a year after hepatectomy, were identified. The DNA methylation status of the 41 BAC clones was correlated with the cancer-free and overall survival rates of patients with HCC. Multivariate analysis revealed that satisfying the criteria using the 41 BAC clones was an independent predictor of overall outcome. Genome-wide alterations of DNA methylation may participate in hepatocarcinogenesis from the precancerous stage, and DNA methylation profiling may provide optimal indicators for carcinogenetic risk estimation and prognostication. |
| تدمد: | 1097-0215 0020-7136 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5902002f8d1ee6b388f40ea5c0554923Test https://doi.org/10.1002/ijc.24708Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5902002f8d1ee6b388f40ea5c0554923 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10970215 00207136 |
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