该研究探讨了早期直肠癌中DNA甲基化模式对于保肛手术的效果及其作为预后标志物的潜力。通过分析不同阶段的直肠癌样本，发现了一种独特的DNA甲基化特征，与局部疾病相关。进一步的研究显示，某些基因如UNC5C的蛋白质表达与淋巴结状态有关，且全基因组扫描揭示了数千个在无淋巴结转移和有淋巴结转移直肠癌之间的差异甲基化基因。部分基因如SNAP25、SOX7和TIAM1的超甲基化与良好的病理指标相关。这些发现为直肠癌的预后生物标记物提供了新的见解，并可能用于风险分层的临床应用。
摘要：
Organ-preservation surgery for early rectal cancer is an alternative treatment to conventional radical surgery that offers comparable oncological outcome but has lower morbidity and mortality. The efficacy of this strategy relies on accurate preoperative staging of mesorectal nodal metastasis which current staging modalities are unable to deliver. DNA methylation has a prognostic role in colorectal carcinogenesis and may select for tumours suitable for local excision, although this has not been explored in rectal cancer. A panel of staged rectal cancers was analysed for differential DNA methylation patterns. This identified a unique signature consisting of concomitant hypermethylation of three or more of APC, RARB, GSTP1, TIMP3, CASP8, DAPK1 and CXCL12 that was associated with histopathologically localised disease. Correlation of protein expression with clinicopathological features found UNC5C expression to be associated with nodal status. Genome-wide screening found >7000 differentially methylated genes between node-negative and node-positive rectal cancer. Validation was performed on a subset of these genes and this confirmed hypermethylation of SNAP25, SOX7 and TIAM1 to be associated with favourable histological indices. This study has provided insight into the methylation patterns of rectal cancer and has identified novel prognostic biomarkers. Further work will determine their clinical usefulness in rectal cancer risk stratification.
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