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MicroRNA‐125b expression and intrahepatic metastasis are predictors for early recurrence after hepatocellular carcinoma resection
Author(s) -
Shimagaki Tomonari,
Yoshizumi Tomoharu,
Harimoto Norifumi,
Yoshio Sachiyo,
Naito Yutaka,
Yamamoto Yusuke,
Ochiya Takahiro,
Yoshida Yoshihiro,
Kanto Tatsuya,
Maehara Yoshihiko
Publication year - 2018
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.12990
Subject(s) - hepatocellular carcinoma , medicine , microrna , metastasis , multivariate analysis , oncology , gastroenterology , pathology , cancer , biology , gene , biochemistry
Aim Early hepatocellular carcinoma (HCC) recurrence after curative resection is a known poor prognostic factor. We aimed to identify microRNAs associated with recurrence after curative HCC resection. Methods To identify risk factors for early recurrence and metastasis, 694 patients who underwent primary curative HCC resection were analyzed. We evaluated microRNA expression in cancerous and non‐cancerous tissues by microarray and quantitative PCR analyses using 16 HCC samples. We defined patients who had a recurrence within 1 year of resection as the early recurrence (ER) group, patients who had a recurrence within 1–5 years as the late recurrence (LR) group, and patients who did not recur during the 5‐year observation period as the no recurrence (NR) group. We examined the relationship between microRNA expression and clinical features. Results Multivariate analysis revealed that α‐fetoprotein >31 ng/mL, tumor size >4 cm, and intrahepatic metastasis (IM) were significant factors. Afterwards, microarray analyses revealed that microRNA (miR)‐125b‐5p and miR‐148a‐3p were significantly downregulated in recurrent cases. The ratio of miR‐125b‐5p expression in cancerous versus non‐cancerous tissue (miR‐125b ratio), but not miR‐148a‐3p, was significantly lower in the ER group. Early recurrence was associated with reduced overall survival compared with the LR and NR group. The miR‐125b ratio was significantly lower in the ER group than in the LR and NR groups. Multivariate analysis showed that a low miR‐125b ratio and IM were independently associated with ER and disease‐free survival. Conclusions Assessing tissue miR‐125b‐5p expression and IM is useful for stratifying patients at risk of early HCC recurrence after curative resection.