Circulating microRNA-1246 as a possible biomarker for early tumor recurrence of hepatocellular carcinoma

Makoto Chuma, Hidenori Toyoda, Juntaro Matsuzaki, Yoshimasa Saito, Takashi Kumada, Toshifumi Tada, Yuji Kaneoka, Atsuyuki Maeda, Hideki Yokoo, Koji Ogawa, Toshiya Kamiyama, Akinobu Taketomi, Yoshihiro Matsuno, Keiichi Yazawa, Kazuhisa Takeda, Chikara Kunisaki, Katsuaki Ogushi, Satoshi Moriya, Koji Hara, Akito NozakiMasaaki Kondo, Hiroyuki Fukuda, Kazushi Numata, Katsuaki Tanaka, Shin Maeda, Naoya Sakamoto

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Aims: Early tumor recurrence (ETR) after hepatic resection is a crucial predictor of poor prognosis in patients with hepatocellular carcinoma (HCC). The aim of this study was to identify clinically significant serum microRNAs (miRNAs) involved in the ETR of HCC. Methods: We compared expression profiles of circulating miRNAs from serum samples between five HCC patients with ETR (recurrence within 12 months after hepatectomy) and five HCC patients without recurrence using microarray analysis of miRNA. The identified miRNA associated with ETR was further verified in 121 HCC patients, 73 liver disease patients, and 15 health controls by real-time quantitative reverse transcription–polymerase chain reaction (PCR). Results: Of the approximately 2000 miRNAs analyzed, we identified 15 miRNAs for which expression levels correlated significantly with ETR. Of these miRNAs, we further investigated expression of miRNA-1246 (miR-1246). Quantitative PCR confirmed that miR-1246 was upregulated in HCC with ETR, compared to the level in HCC without ETR (P < 0.001). Serum miR-1246 showed a receiver operating characteristic curve area of 0.762, with 77.4% specificity and 54.1% sensitivity in discriminating HCC patients with ETR from HCC patients without ETR. Altered expression of miR-1246 was associated with aggressive tumor characteristics, including tumor–node–metastasis classification (P = 0.0413), tumor differentiation (P = 0.0419), and portal vein invasion (P = 0.0394). Moreover, multivariate Cox regression analysis identified serum miR-1246 level as an independent risk factor for overall survival (hazard ratio, 2.784; 95% confidence interval, 1.528–5.071; P = 0.0008). Conclusion: Circulating miR-1246 in serum has strong potential as a novel ETR and prognostic biomarker for HCC.

Original languageEnglish
Pages (from-to)810-822
Number of pages13
JournalHepatology Research
Volume49
Issue number7
DOIs
Publication statusPublished - 2019 Jul 1

Fingerprint

Tumor Biomarkers
MicroRNAs
Hepatocellular Carcinoma
Recurrence
Neoplasms
Serum
Polymerase Chain Reaction
Hepatectomy
Microarray Analysis
Portal Vein
ROC Curve
Liver Diseases
Biomarkers
Regression Analysis
Confidence Intervals

Keywords

  • circulating microRNA
  • early recurrence
  • hepatocellular carcinoma
  • miR-1246prognosis

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases

Cite this

Circulating microRNA-1246 as a possible biomarker for early tumor recurrence of hepatocellular carcinoma. / Chuma, Makoto; Toyoda, Hidenori; Matsuzaki, Juntaro; Saito, Yoshimasa; Kumada, Takashi; Tada, Toshifumi; Kaneoka, Yuji; Maeda, Atsuyuki; Yokoo, Hideki; Ogawa, Koji; Kamiyama, Toshiya; Taketomi, Akinobu; Matsuno, Yoshihiro; Yazawa, Keiichi; Takeda, Kazuhisa; Kunisaki, Chikara; Ogushi, Katsuaki; Moriya, Satoshi; Hara, Koji; Nozaki, Akito; Kondo, Masaaki; Fukuda, Hiroyuki; Numata, Kazushi; Tanaka, Katsuaki; Maeda, Shin; Sakamoto, Naoya.

In: Hepatology Research, Vol. 49, No. 7, 01.07.2019, p. 810-822.

Research output: Contribution to journalArticle

Chuma, M, Toyoda, H, Matsuzaki, J, Saito, Y, Kumada, T, Tada, T, Kaneoka, Y, Maeda, A, Yokoo, H, Ogawa, K, Kamiyama, T, Taketomi, A, Matsuno, Y, Yazawa, K, Takeda, K, Kunisaki, C, Ogushi, K, Moriya, S, Hara, K, Nozaki, A, Kondo, M, Fukuda, H, Numata, K, Tanaka, K, Maeda, S & Sakamoto, N 2019, 'Circulating microRNA-1246 as a possible biomarker for early tumor recurrence of hepatocellular carcinoma', Hepatology Research, vol. 49, no. 7, pp. 810-822. https://doi.org/10.1111/hepr.13338
Chuma, Makoto ; Toyoda, Hidenori ; Matsuzaki, Juntaro ; Saito, Yoshimasa ; Kumada, Takashi ; Tada, Toshifumi ; Kaneoka, Yuji ; Maeda, Atsuyuki ; Yokoo, Hideki ; Ogawa, Koji ; Kamiyama, Toshiya ; Taketomi, Akinobu ; Matsuno, Yoshihiro ; Yazawa, Keiichi ; Takeda, Kazuhisa ; Kunisaki, Chikara ; Ogushi, Katsuaki ; Moriya, Satoshi ; Hara, Koji ; Nozaki, Akito ; Kondo, Masaaki ; Fukuda, Hiroyuki ; Numata, Kazushi ; Tanaka, Katsuaki ; Maeda, Shin ; Sakamoto, Naoya. / Circulating microRNA-1246 as a possible biomarker for early tumor recurrence of hepatocellular carcinoma. In: Hepatology Research. 2019 ; Vol. 49, No. 7. pp. 810-822.
@article{47f9041ead9f4c4d80e7023950825152,
title = "Circulating microRNA-1246 as a possible biomarker for early tumor recurrence of hepatocellular carcinoma",
abstract = "Aims: Early tumor recurrence (ETR) after hepatic resection is a crucial predictor of poor prognosis in patients with hepatocellular carcinoma (HCC). The aim of this study was to identify clinically significant serum microRNAs (miRNAs) involved in the ETR of HCC. Methods: We compared expression profiles of circulating miRNAs from serum samples between five HCC patients with ETR (recurrence within 12 months after hepatectomy) and five HCC patients without recurrence using microarray analysis of miRNA. The identified miRNA associated with ETR was further verified in 121 HCC patients, 73 liver disease patients, and 15 health controls by real-time quantitative reverse transcription–polymerase chain reaction (PCR). Results: Of the approximately 2000 miRNAs analyzed, we identified 15 miRNAs for which expression levels correlated significantly with ETR. Of these miRNAs, we further investigated expression of miRNA-1246 (miR-1246). Quantitative PCR confirmed that miR-1246 was upregulated in HCC with ETR, compared to the level in HCC without ETR (P < 0.001). Serum miR-1246 showed a receiver operating characteristic curve area of 0.762, with 77.4{\%} specificity and 54.1{\%} sensitivity in discriminating HCC patients with ETR from HCC patients without ETR. Altered expression of miR-1246 was associated with aggressive tumor characteristics, including tumor–node–metastasis classification (P = 0.0413), tumor differentiation (P = 0.0419), and portal vein invasion (P = 0.0394). Moreover, multivariate Cox regression analysis identified serum miR-1246 level as an independent risk factor for overall survival (hazard ratio, 2.784; 95{\%} confidence interval, 1.528–5.071; P = 0.0008). Conclusion: Circulating miR-1246 in serum has strong potential as a novel ETR and prognostic biomarker for HCC.",
keywords = "circulating microRNA, early recurrence, hepatocellular carcinoma, miR-1246prognosis",
author = "Makoto Chuma and Hidenori Toyoda and Juntaro Matsuzaki and Yoshimasa Saito and Takashi Kumada and Toshifumi Tada and Yuji Kaneoka and Atsuyuki Maeda and Hideki Yokoo and Koji Ogawa and Toshiya Kamiyama and Akinobu Taketomi and Yoshihiro Matsuno and Keiichi Yazawa and Kazuhisa Takeda and Chikara Kunisaki and Katsuaki Ogushi and Satoshi Moriya and Koji Hara and Akito Nozaki and Masaaki Kondo and Hiroyuki Fukuda and Kazushi Numata and Katsuaki Tanaka and Shin Maeda and Naoya Sakamoto",
year = "2019",
month = "7",
day = "1",
doi = "10.1111/hepr.13338",
language = "English",
volume = "49",
pages = "810--822",
journal = "Hepatology Research",
issn = "1386-6346",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "7",

}

TY - JOUR

T1 - Circulating microRNA-1246 as a possible biomarker for early tumor recurrence of hepatocellular carcinoma

AU - Chuma, Makoto

AU - Toyoda, Hidenori

AU - Matsuzaki, Juntaro

AU - Saito, Yoshimasa

AU - Kumada, Takashi

AU - Tada, Toshifumi

AU - Kaneoka, Yuji

AU - Maeda, Atsuyuki

AU - Yokoo, Hideki

AU - Ogawa, Koji

AU - Kamiyama, Toshiya

AU - Taketomi, Akinobu

AU - Matsuno, Yoshihiro

AU - Yazawa, Keiichi

AU - Takeda, Kazuhisa

AU - Kunisaki, Chikara

AU - Ogushi, Katsuaki

AU - Moriya, Satoshi

AU - Hara, Koji

AU - Nozaki, Akito

AU - Kondo, Masaaki

AU - Fukuda, Hiroyuki

AU - Numata, Kazushi

AU - Tanaka, Katsuaki

AU - Maeda, Shin

AU - Sakamoto, Naoya

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Aims: Early tumor recurrence (ETR) after hepatic resection is a crucial predictor of poor prognosis in patients with hepatocellular carcinoma (HCC). The aim of this study was to identify clinically significant serum microRNAs (miRNAs) involved in the ETR of HCC. Methods: We compared expression profiles of circulating miRNAs from serum samples between five HCC patients with ETR (recurrence within 12 months after hepatectomy) and five HCC patients without recurrence using microarray analysis of miRNA. The identified miRNA associated with ETR was further verified in 121 HCC patients, 73 liver disease patients, and 15 health controls by real-time quantitative reverse transcription–polymerase chain reaction (PCR). Results: Of the approximately 2000 miRNAs analyzed, we identified 15 miRNAs for which expression levels correlated significantly with ETR. Of these miRNAs, we further investigated expression of miRNA-1246 (miR-1246). Quantitative PCR confirmed that miR-1246 was upregulated in HCC with ETR, compared to the level in HCC without ETR (P < 0.001). Serum miR-1246 showed a receiver operating characteristic curve area of 0.762, with 77.4% specificity and 54.1% sensitivity in discriminating HCC patients with ETR from HCC patients without ETR. Altered expression of miR-1246 was associated with aggressive tumor characteristics, including tumor–node–metastasis classification (P = 0.0413), tumor differentiation (P = 0.0419), and portal vein invasion (P = 0.0394). Moreover, multivariate Cox regression analysis identified serum miR-1246 level as an independent risk factor for overall survival (hazard ratio, 2.784; 95% confidence interval, 1.528–5.071; P = 0.0008). Conclusion: Circulating miR-1246 in serum has strong potential as a novel ETR and prognostic biomarker for HCC.

AB - Aims: Early tumor recurrence (ETR) after hepatic resection is a crucial predictor of poor prognosis in patients with hepatocellular carcinoma (HCC). The aim of this study was to identify clinically significant serum microRNAs (miRNAs) involved in the ETR of HCC. Methods: We compared expression profiles of circulating miRNAs from serum samples between five HCC patients with ETR (recurrence within 12 months after hepatectomy) and five HCC patients without recurrence using microarray analysis of miRNA. The identified miRNA associated with ETR was further verified in 121 HCC patients, 73 liver disease patients, and 15 health controls by real-time quantitative reverse transcription–polymerase chain reaction (PCR). Results: Of the approximately 2000 miRNAs analyzed, we identified 15 miRNAs for which expression levels correlated significantly with ETR. Of these miRNAs, we further investigated expression of miRNA-1246 (miR-1246). Quantitative PCR confirmed that miR-1246 was upregulated in HCC with ETR, compared to the level in HCC without ETR (P < 0.001). Serum miR-1246 showed a receiver operating characteristic curve area of 0.762, with 77.4% specificity and 54.1% sensitivity in discriminating HCC patients with ETR from HCC patients without ETR. Altered expression of miR-1246 was associated with aggressive tumor characteristics, including tumor–node–metastasis classification (P = 0.0413), tumor differentiation (P = 0.0419), and portal vein invasion (P = 0.0394). Moreover, multivariate Cox regression analysis identified serum miR-1246 level as an independent risk factor for overall survival (hazard ratio, 2.784; 95% confidence interval, 1.528–5.071; P = 0.0008). Conclusion: Circulating miR-1246 in serum has strong potential as a novel ETR and prognostic biomarker for HCC.

KW - circulating microRNA

KW - early recurrence

KW - hepatocellular carcinoma

KW - miR-1246prognosis

UR - http://www.scopus.com/inward/record.url?scp=85066904117&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85066904117&partnerID=8YFLogxK

U2 - 10.1111/hepr.13338

DO - 10.1111/hepr.13338

M3 - Article

AN - SCOPUS:85066904117

VL - 49

SP - 810

EP - 822

JO - Hepatology Research

JF - Hepatology Research

SN - 1386-6346

IS - 7

ER -