Prognostic value of LINE-1 methylation level in 321 patients with primary liver cancer including hepatocellular carcinoma and intrahepatic cholangiocarcinoma

Tatsunori Miyata; Yo Ichi Yamashita; Yoshifumi Baba; Kazuto Harada; Takanobu Yamao; Naoki Umezaki; Masayo Tsukamoto; Yuki Kitano; Kensuke Yamamura; Kota Arima; Shigeki Nakagawa; Hirohisa Okabe; Katsunori Imai; Daisuke Hashimoto; Akira Chikamoto; Mototsugu Shimokawa; Hideo Baba

doi:10.18632/oncotarget.25124

Prognostic value of LINE-1 methylation level in 321 patients with primary liver cancer including hepatocellular carcinoma and intrahepatic cholangiocarcinoma

Tatsunori Miyata, Yo Ichi Yamashita, Yoshifumi Baba, Kazuto Harada, Takanobu Yamao, Naoki Umezaki, Masayo Tsukamoto, Yuki Kitano, Kensuke Yamamura, Kota Arima, Shigeki Nakagawa, Hirohisa Okabe, Katsunori Imai, Daisuke Hashimoto, Akira Chikamoto, Mototsugu Shimokawa, Hideo Baba

Cancer Prevention Training Program

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Background: The methylation level of long interspersed nucleotide element-1 (LINE-1) is a good surrogate marker of the global DNA methylation level. The relationship between LINE-1 methylation level and prognosis in primary liver cancer (PLC) patients remains unclear. Results: LINE-1 methylation levels were significantly lower in HCC and cHCC-CC tissues, but not in ICC tissues, than those in noncancerous liver parenchyma (HCC: p < 0.0001; cHCC-CC: p < 0.001; and ICC: p = 0.053). HCC cases with hypomethylated LINE-1 had significantly shorter relapse-free survival (RFS) (log-rank, p = 0.008); however, this was not observed for the cHCC-CC or ICC cases. Multivariate Cox regression analysis revealed a significantly higher HCC recurrence rate in the group with hypomethylated LINE-1 (hazard ratio, 1.62; 95% confidence interval, 1.06-2.58; p = 0.025). Conclusions: The genome-wide DNA hypomethylation status estimated via LINE-1 methylation levels might be indicative of poor RFS in patients with HCC but not ICC or cHCC-CC. Methods: We evaluated the level of LINE-1 methylation in 321 cases of curatively resected PLC [231 hepatocellular carcinoma (HCC), 19 combined hepatocellular and cholangiocarcinoma (cHCC-CC) and 71 intrahepatic cholangiocarcinoma (ICC)] via pyrosequencing of formalin-fixed paraffin-embedded (FFPE) tissues and examined its prognostic value.

Original language	English (US)
Pages (from-to)	20795-20806
Number of pages	12
Journal	Oncotarget
Volume	9
Issue number	29
DOIs	https://doi.org/10.18632/oncotarget.25124
State	Published - Apr 17 2018

Keywords

Epigenetics
LINE-1
Methylation
Primary liver cancer
Prognosis

ASJC Scopus subject areas

Oncology

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10.18632/oncotarget.25124

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Miyata, T., Yamashita, Y. I., Baba, Y., Harada, K., Yamao, T., Umezaki, N., Tsukamoto, M., Kitano, Y., Yamamura, K., Arima, K., Nakagawa, S., Okabe, H., Imai, K., Hashimoto, D., Chikamoto, A., Shimokawa, M., & Baba, H. (2018). Prognostic value of LINE-1 methylation level in 321 patients with primary liver cancer including hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Oncotarget, 9(29), 20795-20806. https://doi.org/10.18632/oncotarget.25124

Miyata, T, Yamashita, YI, Baba, Y, Harada, K, Yamao, T, Umezaki, N, Tsukamoto, M, Kitano, Y, Yamamura, K, Arima, K, Nakagawa, S, Okabe, H, Imai, K, Hashimoto, D, Chikamoto, A, Shimokawa, M & Baba, H 2018, 'Prognostic value of LINE-1 methylation level in 321 patients with primary liver cancer including hepatocellular carcinoma and intrahepatic cholangiocarcinoma', Oncotarget, vol. 9, no. 29, pp. 20795-20806. https://doi.org/10.18632/oncotarget.25124

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title = "Prognostic value of LINE-1 methylation level in 321 patients with primary liver cancer including hepatocellular carcinoma and intrahepatic cholangiocarcinoma",

abstract = "Background: The methylation level of long interspersed nucleotide element-1 (LINE-1) is a good surrogate marker of the global DNA methylation level. The relationship between LINE-1 methylation level and prognosis in primary liver cancer (PLC) patients remains unclear. Results: LINE-1 methylation levels were significantly lower in HCC and cHCC-CC tissues, but not in ICC tissues, than those in noncancerous liver parenchyma (HCC: p < 0.0001; cHCC-CC: p < 0.001; and ICC: p = 0.053). HCC cases with hypomethylated LINE-1 had significantly shorter relapse-free survival (RFS) (log-rank, p = 0.008); however, this was not observed for the cHCC-CC or ICC cases. Multivariate Cox regression analysis revealed a significantly higher HCC recurrence rate in the group with hypomethylated LINE-1 (hazard ratio, 1.62; 95% confidence interval, 1.06-2.58; p = 0.025). Conclusions: The genome-wide DNA hypomethylation status estimated via LINE-1 methylation levels might be indicative of poor RFS in patients with HCC but not ICC or cHCC-CC. Methods: We evaluated the level of LINE-1 methylation in 321 cases of curatively resected PLC [231 hepatocellular carcinoma (HCC), 19 combined hepatocellular and cholangiocarcinoma (cHCC-CC) and 71 intrahepatic cholangiocarcinoma (ICC)] via pyrosequencing of formalin-fixed paraffin-embedded (FFPE) tissues and examined its prognostic value.",

keywords = "Epigenetics, LINE-1, Methylation, Primary liver cancer, Prognosis",

author = "Tatsunori Miyata and Yamashita, {Yo Ichi} and Yoshifumi Baba and Kazuto Harada and Takanobu Yamao and Naoki Umezaki and Masayo Tsukamoto and Yuki Kitano and Kensuke Yamamura and Kota Arima and Shigeki Nakagawa and Hirohisa Okabe and Katsunori Imai and Daisuke Hashimoto and Akira Chikamoto and Mototsugu Shimokawa and Hideo Baba",

note = "Publisher Copyright: {\textcopyright} Miyata et al.",

year = "2018",

month = apr,

day = "17",

doi = "10.18632/oncotarget.25124",

language = "English (US)",

volume = "9",

pages = "20795--20806",

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TY - JOUR

T1 - Prognostic value of LINE-1 methylation level in 321 patients with primary liver cancer including hepatocellular carcinoma and intrahepatic cholangiocarcinoma

AU - Miyata, Tatsunori

AU - Yamashita, Yo Ichi

AU - Baba, Yoshifumi

AU - Harada, Kazuto

AU - Yamao, Takanobu

AU - Umezaki, Naoki

AU - Tsukamoto, Masayo

AU - Kitano, Yuki

AU - Yamamura, Kensuke

AU - Arima, Kota

AU - Nakagawa, Shigeki

AU - Okabe, Hirohisa

AU - Imai, Katsunori

AU - Hashimoto, Daisuke

AU - Chikamoto, Akira

AU - Shimokawa, Mototsugu

AU - Baba, Hideo

PY - 2018/4/17

Y1 - 2018/4/17

N2 - Background: The methylation level of long interspersed nucleotide element-1 (LINE-1) is a good surrogate marker of the global DNA methylation level. The relationship between LINE-1 methylation level and prognosis in primary liver cancer (PLC) patients remains unclear. Results: LINE-1 methylation levels were significantly lower in HCC and cHCC-CC tissues, but not in ICC tissues, than those in noncancerous liver parenchyma (HCC: p < 0.0001; cHCC-CC: p < 0.001; and ICC: p = 0.053). HCC cases with hypomethylated LINE-1 had significantly shorter relapse-free survival (RFS) (log-rank, p = 0.008); however, this was not observed for the cHCC-CC or ICC cases. Multivariate Cox regression analysis revealed a significantly higher HCC recurrence rate in the group with hypomethylated LINE-1 (hazard ratio, 1.62; 95% confidence interval, 1.06-2.58; p = 0.025). Conclusions: The genome-wide DNA hypomethylation status estimated via LINE-1 methylation levels might be indicative of poor RFS in patients with HCC but not ICC or cHCC-CC. Methods: We evaluated the level of LINE-1 methylation in 321 cases of curatively resected PLC [231 hepatocellular carcinoma (HCC), 19 combined hepatocellular and cholangiocarcinoma (cHCC-CC) and 71 intrahepatic cholangiocarcinoma (ICC)] via pyrosequencing of formalin-fixed paraffin-embedded (FFPE) tissues and examined its prognostic value.

AB - Background: The methylation level of long interspersed nucleotide element-1 (LINE-1) is a good surrogate marker of the global DNA methylation level. The relationship between LINE-1 methylation level and prognosis in primary liver cancer (PLC) patients remains unclear. Results: LINE-1 methylation levels were significantly lower in HCC and cHCC-CC tissues, but not in ICC tissues, than those in noncancerous liver parenchyma (HCC: p < 0.0001; cHCC-CC: p < 0.001; and ICC: p = 0.053). HCC cases with hypomethylated LINE-1 had significantly shorter relapse-free survival (RFS) (log-rank, p = 0.008); however, this was not observed for the cHCC-CC or ICC cases. Multivariate Cox regression analysis revealed a significantly higher HCC recurrence rate in the group with hypomethylated LINE-1 (hazard ratio, 1.62; 95% confidence interval, 1.06-2.58; p = 0.025). Conclusions: The genome-wide DNA hypomethylation status estimated via LINE-1 methylation levels might be indicative of poor RFS in patients with HCC but not ICC or cHCC-CC. Methods: We evaluated the level of LINE-1 methylation in 321 cases of curatively resected PLC [231 hepatocellular carcinoma (HCC), 19 combined hepatocellular and cholangiocarcinoma (cHCC-CC) and 71 intrahepatic cholangiocarcinoma (ICC)] via pyrosequencing of formalin-fixed paraffin-embedded (FFPE) tissues and examined its prognostic value.

KW - Epigenetics

KW - LINE-1

KW - Methylation

KW - Primary liver cancer

KW - Prognosis

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U2 - 10.18632/oncotarget.25124

DO - 10.18632/oncotarget.25124

M3 - Article

C2 - 29755690

AN - SCOPUS:85045532111

SN - 1949-2553

VL - 9

SP - 20795

EP - 20806

JO - Oncotarget

JF - Oncotarget

IS - 29

ER -

Prognostic value of LINE-1 methylation level in 321 patients with primary liver cancer including hepatocellular carcinoma and intrahepatic cholangiocarcinoma

Abstract

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