Coexpression of SALL4 with HDAC1 and/or HDAC2 is associated with underexpression of PTEN and poor prognosis in patients with hepatocellular carcinoma

Huanlin Wang, Kenichi Kouhashi, Tomoharu Yoshizumi, Yukihiko Okumura, Yuki Tanaka, Masahiro Shimokawa, Takeshi Iwasaki, Shinichi Aishima, Yoshihiko Maehara, Yoshinao Oda

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Abstract

Spalt-like transcriptional factor 4 (SALL4), a stem marker, is reactivated in several cancers. A previous study has demonstrated that SALL4 interacts with the nucleosome remodeling deacetylase complex, which contains histone deacetylase 1 (HDAC1) and histone deacetylase 2 (HDAC2). In this study, we investigated the expression status of SALL4, HDAC1, and HDAC2 and their relationship with phosphatase and tensin homolog deleted on chromosome 10 (PTEN) by immunohistochemical analysis of the posthepatectomy specimens of 135 patients with hepatocellular carcinoma who were treated at our hospital. Ninety-two frozen samples were subjected to quantitative reverse-transcription polymerase chain reaction analysis to detect the messenger RNA levels of PTEN. Seventy-six (56%) of 135 patients were positive for SALL4, and this group had a higher prevalence of hepatitis B antigen, a higher value of α-fetoprotein (AFP) and protein induced by vitamin K absence (PIVKAII) and poor histologic differentiation. The 5-year survival rate was significantly lower in the SALL4-positive group. High HDAC1 expression (51%) was correlated with a poor histologic differentiation and a poor prognosis. High HDAC2 expression (46%) was associated with a higher prevalence of hepatitis B antigen positivity, a poor histologic differentiation and higher prevalence of vascular invasion, and a lower 5-year survival rate. Coexpression of SALL4 with HDAC1 and/or HDAC2 was correlated with underexpression of PTEN. Moreover, multivariable analysis revealed that coexpression of SALL4 with HDAC1 and/or HDAC2 was predictive of an unfavorable prognosis. Our data thus suggested that the combination of SALL4, HDAC1, and HDAC2 may provide a potential target for molecular therapy.

Original languageEnglish
Pages (from-to)69-75
Number of pages7
JournalHuman Pathology
Volume64
DOIs
Publication statusPublished - Jun 1 2017

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Histone Deacetylase 2
Histone Deacetylase 1
Hepatocellular Carcinoma
Hepatitis B Antigens
Mi-2 Nucleosome Remodeling and Deacetylase Complex
Survival Rate
Fetal Proteins
Chromosomes, Human, Pair 10
Vitamin K
Phosphoric Monoester Hydrolases
Reverse Transcription
Blood Vessels
Polymerase Chain Reaction
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Coexpression of SALL4 with HDAC1 and/or HDAC2 is associated with underexpression of PTEN and poor prognosis in patients with hepatocellular carcinoma. / Wang, Huanlin; Kouhashi, Kenichi; Yoshizumi, Tomoharu; Okumura, Yukihiko; Tanaka, Yuki; Shimokawa, Masahiro; Iwasaki, Takeshi; Aishima, Shinichi; Maehara, Yoshihiko; Oda, Yoshinao.

In: Human Pathology, Vol. 64, 01.06.2017, p. 69-75.

Research output: Contribution to journalArticle

Wang, Huanlin ; Kouhashi, Kenichi ; Yoshizumi, Tomoharu ; Okumura, Yukihiko ; Tanaka, Yuki ; Shimokawa, Masahiro ; Iwasaki, Takeshi ; Aishima, Shinichi ; Maehara, Yoshihiko ; Oda, Yoshinao. / Coexpression of SALL4 with HDAC1 and/or HDAC2 is associated with underexpression of PTEN and poor prognosis in patients with hepatocellular carcinoma. In: Human Pathology. 2017 ; Vol. 64. pp. 69-75.
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abstract = "Spalt-like transcriptional factor 4 (SALL4), a stem marker, is reactivated in several cancers. A previous study has demonstrated that SALL4 interacts with the nucleosome remodeling deacetylase complex, which contains histone deacetylase 1 (HDAC1) and histone deacetylase 2 (HDAC2). In this study, we investigated the expression status of SALL4, HDAC1, and HDAC2 and their relationship with phosphatase and tensin homolog deleted on chromosome 10 (PTEN) by immunohistochemical analysis of the posthepatectomy specimens of 135 patients with hepatocellular carcinoma who were treated at our hospital. Ninety-two frozen samples were subjected to quantitative reverse-transcription polymerase chain reaction analysis to detect the messenger RNA levels of PTEN. Seventy-six (56{\%}) of 135 patients were positive for SALL4, and this group had a higher prevalence of hepatitis B antigen, a higher value of α-fetoprotein (AFP) and protein induced by vitamin K absence (PIVKAII) and poor histologic differentiation. The 5-year survival rate was significantly lower in the SALL4-positive group. High HDAC1 expression (51{\%}) was correlated with a poor histologic differentiation and a poor prognosis. High HDAC2 expression (46{\%}) was associated with a higher prevalence of hepatitis B antigen positivity, a poor histologic differentiation and higher prevalence of vascular invasion, and a lower 5-year survival rate. Coexpression of SALL4 with HDAC1 and/or HDAC2 was correlated with underexpression of PTEN. Moreover, multivariable analysis revealed that coexpression of SALL4 with HDAC1 and/or HDAC2 was predictive of an unfavorable prognosis. Our data thus suggested that the combination of SALL4, HDAC1, and HDAC2 may provide a potential target for molecular therapy.",
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T1 - Coexpression of SALL4 with HDAC1 and/or HDAC2 is associated with underexpression of PTEN and poor prognosis in patients with hepatocellular carcinoma

AU - Wang, Huanlin

AU - Kouhashi, Kenichi

AU - Yoshizumi, Tomoharu

AU - Okumura, Yukihiko

AU - Tanaka, Yuki

AU - Shimokawa, Masahiro

AU - Iwasaki, Takeshi

AU - Aishima, Shinichi

AU - Maehara, Yoshihiko

AU - Oda, Yoshinao

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Spalt-like transcriptional factor 4 (SALL4), a stem marker, is reactivated in several cancers. A previous study has demonstrated that SALL4 interacts with the nucleosome remodeling deacetylase complex, which contains histone deacetylase 1 (HDAC1) and histone deacetylase 2 (HDAC2). In this study, we investigated the expression status of SALL4, HDAC1, and HDAC2 and their relationship with phosphatase and tensin homolog deleted on chromosome 10 (PTEN) by immunohistochemical analysis of the posthepatectomy specimens of 135 patients with hepatocellular carcinoma who were treated at our hospital. Ninety-two frozen samples were subjected to quantitative reverse-transcription polymerase chain reaction analysis to detect the messenger RNA levels of PTEN. Seventy-six (56%) of 135 patients were positive for SALL4, and this group had a higher prevalence of hepatitis B antigen, a higher value of α-fetoprotein (AFP) and protein induced by vitamin K absence (PIVKAII) and poor histologic differentiation. The 5-year survival rate was significantly lower in the SALL4-positive group. High HDAC1 expression (51%) was correlated with a poor histologic differentiation and a poor prognosis. High HDAC2 expression (46%) was associated with a higher prevalence of hepatitis B antigen positivity, a poor histologic differentiation and higher prevalence of vascular invasion, and a lower 5-year survival rate. Coexpression of SALL4 with HDAC1 and/or HDAC2 was correlated with underexpression of PTEN. Moreover, multivariable analysis revealed that coexpression of SALL4 with HDAC1 and/or HDAC2 was predictive of an unfavorable prognosis. Our data thus suggested that the combination of SALL4, HDAC1, and HDAC2 may provide a potential target for molecular therapy.

AB - Spalt-like transcriptional factor 4 (SALL4), a stem marker, is reactivated in several cancers. A previous study has demonstrated that SALL4 interacts with the nucleosome remodeling deacetylase complex, which contains histone deacetylase 1 (HDAC1) and histone deacetylase 2 (HDAC2). In this study, we investigated the expression status of SALL4, HDAC1, and HDAC2 and their relationship with phosphatase and tensin homolog deleted on chromosome 10 (PTEN) by immunohistochemical analysis of the posthepatectomy specimens of 135 patients with hepatocellular carcinoma who were treated at our hospital. Ninety-two frozen samples were subjected to quantitative reverse-transcription polymerase chain reaction analysis to detect the messenger RNA levels of PTEN. Seventy-six (56%) of 135 patients were positive for SALL4, and this group had a higher prevalence of hepatitis B antigen, a higher value of α-fetoprotein (AFP) and protein induced by vitamin K absence (PIVKAII) and poor histologic differentiation. The 5-year survival rate was significantly lower in the SALL4-positive group. High HDAC1 expression (51%) was correlated with a poor histologic differentiation and a poor prognosis. High HDAC2 expression (46%) was associated with a higher prevalence of hepatitis B antigen positivity, a poor histologic differentiation and higher prevalence of vascular invasion, and a lower 5-year survival rate. Coexpression of SALL4 with HDAC1 and/or HDAC2 was correlated with underexpression of PTEN. Moreover, multivariable analysis revealed that coexpression of SALL4 with HDAC1 and/or HDAC2 was predictive of an unfavorable prognosis. Our data thus suggested that the combination of SALL4, HDAC1, and HDAC2 may provide a potential target for molecular therapy.

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