signature=a5ccaeaf32c935c837a9f1afae7e0845,5‐Hydroxymethylcytosine signature in circulating cell‐fre...-优快云博客

研究通过全基因组5hmC分析，对比了早期结直肠癌（CRC）、腺瘤患者和健康对照组的cfDNA和组织gDNA，发现5hmC修饰在疾病进展中具有特征性变化。CRC和AD患者显示出独特的5hmC信号，而与腺瘤历史相关的5hmC改变可能揭示“平行”演化的证据。这些发现强调了5hmC修饰在不同病理亚型中的潜在诊断价值，为早期CRC筛查和腺瘤恶性潜能评估提供了新的方向。

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摘要：

Approximately 85% Colorectal cancers (CRCs) are thought to evolve through the adenoma‐toヽarcinoma sequence associated with specific molecular alterations, including the 5﹉ydroxymethylcytosine (5hmC) signature in circulating cell‐free DNA (cfDNA). To explore colorectal disease progression and evaluate the use of cfDNA as a potential diagnostic factor for CRC screening, here, we performed genome﹚ide 5hmC profiling in plasma cfDNA and tissue genomic DNA (gDNA) acquired from 101 samples (63 plasma and 38 tissues), collected from 21 early﹕tage CRC patients, 21 AD patients and 21 healthy controls (HC). The gDNA and cfDNA 5hmC signatures identified in gene bodies and promoter regions in CRC and AD groups were compared with those in HC group. All the differential 5hmC﹎odified regions (DhMRs) were gathered into 4 clusters: Disease enriched, AD enriched, Disease lost, and AD lost, with no overlap. AD‐related clusters, AD enriched and AD lost, displayed the unique 5hmC signals in AD patients. Disease enriched and Disease lost clusters indicated the general 5hmC changes when colorectal lesions occurred. Cancer patients with a confirmable adenoma history segmentally gathered in AD〆nriched clusters. KEGG functional enrichment and GO analyses determined distinct differential 5hmC﹎odified profiles in cfDNA of HC individuals, AD and CRC patients. All patients had comprehensive 5hmC signatures where Disease enriched and Disease lost DhMR clusters demonstrated similar epigenetic modifications, while AD enriched and AD lost DhMR clusters indicated complicated subpopulations in adenoma. Analysis of CRC patients with adenoma history showed exclusive 5hmCゞain characteristics, consistent with the "parallel" evolution hypothesis in adenoma, either developed through the adenoma‐toヽarcinoma sequence or not. These findings deepen our understanding of colorectal disease and suggest that the 5hmC modifications of different pathological subtypes (cancer patients with or without adenoma history) could be used to screen early﹕tage CRC and assess adenoma malignancy with large﹕cale follow矔恥dies in the future.

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