切除 HCC 及背景肝组织中甲基化 RNA 及其去甲基酶的新预后意义。
Novel Prognostic Implications of Methylated RNA and Demethylases in Resected HCC and Background Liver Tissue.
机构信息
Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
出版信息
Anticancer Res. 2020 Dec;40(12):6665-6676. doi: 10.21873/anticanres.14690.
BACKGROUND/AIM: N6-Methyladenosine (m6A), the most abundant internal modification of RNA, plays a critical role in cancer development. However, the clinical implications of mA in hepatocellular carcinoma (HCC) remain unclear.
MATERIALS AND METHODS
We analyzed 177 HCC and paired noncancerous liver tissues from patients who underwent hepatectomy according to global mA quantification and expression of mA demethylases fat mass and obesity-associated protein (FTO) and alpha-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5).
RESULTS
The global mA quantification revealed no significant difference between HCC and non-cancerous tissue. The expression of mA demethylases FTO and ALKBH5, was significantly lower in HCC than in non-cancerous tissues (both p<0.001). Furthermore, low ALKBH5 expression in non-cancerous tissues was significantly correlated with worse recurrence-free survival (median of 16.3 vs. 38.9 months, p=0.001).
CONCLUSION
mA in HCC and its demethylase in surrounding non-cancerous liver tissues might be involved in inherent mechanisms for HCC development and affect malignant potential after HCC resection.
背景/目的：N6-甲基腺苷（m6A）是 RNA 中最丰富的内部修饰物，在癌症发展中起着关键作用。然而，m6A 在肝细胞癌（HCC）中的临床意义尚不清楚。
材料和方法
我们根据全球 m6A 定量和 m6A 去甲基酶脂肪量和肥胖相关蛋白（FTO）和α-酮戊二酸依赖性双加氧酶 alkB 同源物 5（ALKBH5）的表达，分析了 177 例接受肝切除术的 HCC 和配对的非癌性肝组织。
结果
全球 m6A 定量显示 HCC 和非癌组织之间没有显著差异。mA 去甲基酶 FTO 和 ALKBH5 的表达在 HCC 中明显低于非癌组织（均 p<0.001）。此外，非癌组织中低表达 ALKBH5 与无复发生存率显著相关（中位数为 16.3 与 38.9 个月，p=0.001）。
结论
HCC 中的 m6A 及其周围非癌性肝组织中的去甲基酶可能参与 HCC 发展的固有机制，并影响 HCC 切除后的恶性潜能。
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