Journal
ANTICANCER RESEARCH
Volume 40, Issue 12, Pages 6665-6676Publisher
INT INST ANTICANCER RESEARCH
DOI: 10.21873/anticanres.14690
Keywords
Hepatocellular carcinoma; methylation of N6 adenosine; RNA demethylase; prognosis
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Funding
- Japan Society for the Promotion of Science (JSPS) KAKENHI [18H06176, 19K18110]
- Grants-in-Aid for Scientific Research [19K18110, 18H06176] Funding Source: KAKEN
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Background/Aim: N6-Methyladenosine (m6A), the most abundant internal modification of RNA, plays a critical role in cancer development. However, the clinical implications of m6A in hepatocellular carcinoma (HCC) remain unclear. Materials and Methods: We analyzed 177 HCC and paired non-cancerous liver tissues from patients who underwent hepatectomy according to global m6A quantification and expression of m6A demethylases fat mass and obesity-associated protein (FTO) and alpha-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5). Results: The global m6A quantification revealed no significant difference between HCC and non-cancerous tissue. The expression of m6A 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: m6A 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.
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