Clinical significance of PICT1 in patients of hepatocellular carcinoma with wild-type TP53

Masahisa Ishibashi, Ryunosuke Kogo, Kohei Shibata, Hiroki Ueo, Ryutaro Uchi, Tae Matsumura, Yuki Takano, Genta Sawada, Yusuke Takahashi, Kousuke Mima, Junji Kurashige, Sayuri Akiyoshi, Takeshi Iwaya, Hidetoshi Eguchi, Tomoya Sudo, Keishi Sugimachi, Akira Suzuki, Go Wakabayashi, Masaki Mori, Koshi Mimori

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background. TP53 is one of the most widely known cancer suppressor genes. Mutations in TP53 are ubiquitously observed in almost all cancers. Incidences of mutations range from *15-70 % in patients with hepatocellular carcinoma (HCC). Moreover, patients with mutated TP53 have poorer prognoses than those with wildtype TP53; therefore, it would be beneficial to predict the prognosis of HCC patients with wild-type TP53. We previously reported that PICT1, coding a nucleolus protein, regulates TP53 through indirect association. Methods. In this study, we examined PICT1 expression levels and the status of TP53 in 51 primary HCC tissues in order to determine the clinical significance of PICT1 expression and the function of PICT1 in HCC cells. Results. We detected 6 mutations in the 51 samples. In 45 patients with wild-type TP53, those with high PICT1 expression (n = 11) had poorer prognoses than those with low PICT1 expression (n = 34), and there were no significant associations with other clinicopathological factors. According to gene set enrichment analysis, PICT1 expression was inversely correlated with the gene set of TP53. In vitro assays indicated that suppression of PICT1 expression caused an increase in TP53 expression, reduction in cell proliferation, and arrest at the G1 phase of the cell cycle in HCC cells expressing wild-type TP53. Conclusions. PICT1 should be a useful prognosticmarker in HCC patients having wild-type TP53. Furthermore, PICT1 may become a promising therapeutic target because of its ability to increase the expression and activation of TP53.

Original languageEnglish
Pages (from-to)S537-S544
JournalAnnals of Surgical Oncology
Volume20
Issue number3 SUPPL.
DOIs
Publication statusPublished - Mar 27 2013

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Hepatocellular Carcinoma
Mutation
Tumor Suppressor Protein p53
p53 Genes
G1 Phase
Tumor Suppressor Genes
Cell Cycle
Cell Proliferation
Incidence
Genes
Neoplasms
Therapeutics

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

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Clinical significance of PICT1 in patients of hepatocellular carcinoma with wild-type TP53. / Ishibashi, Masahisa; Kogo, Ryunosuke; Shibata, Kohei; Ueo, Hiroki; Uchi, Ryutaro; Matsumura, Tae; Takano, Yuki; Sawada, Genta; Takahashi, Yusuke; Mima, Kousuke; Kurashige, Junji; Akiyoshi, Sayuri; Iwaya, Takeshi; Eguchi, Hidetoshi; Sudo, Tomoya; Sugimachi, Keishi; Suzuki, Akira; Wakabayashi, Go; Mori, Masaki; Mimori, Koshi.

In: Annals of Surgical Oncology, Vol. 20, No. 3 SUPPL., 27.03.2013, p. S537-S544.

Research output: Contribution to journalArticle

Ishibashi, M, Kogo, R, Shibata, K, Ueo, H, Uchi, R, Matsumura, T, Takano, Y, Sawada, G, Takahashi, Y, Mima, K, Kurashige, J, Akiyoshi, S, Iwaya, T, Eguchi, H, Sudo, T, Sugimachi, K, Suzuki, A, Wakabayashi, G, Mori, M & Mimori, K 2013, 'Clinical significance of PICT1 in patients of hepatocellular carcinoma with wild-type TP53', Annals of Surgical Oncology, vol. 20, no. 3 SUPPL., pp. S537-S544. https://doi.org/10.1245/s10434-013-2958-x
Ishibashi M, Kogo R, Shibata K, Ueo H, Uchi R, Matsumura T et al. Clinical significance of PICT1 in patients of hepatocellular carcinoma with wild-type TP53. Annals of Surgical Oncology. 2013 Mar 27;20(3 SUPPL.):S537-S544. https://doi.org/10.1245/s10434-013-2958-x
Ishibashi, Masahisa ; Kogo, Ryunosuke ; Shibata, Kohei ; Ueo, Hiroki ; Uchi, Ryutaro ; Matsumura, Tae ; Takano, Yuki ; Sawada, Genta ; Takahashi, Yusuke ; Mima, Kousuke ; Kurashige, Junji ; Akiyoshi, Sayuri ; Iwaya, Takeshi ; Eguchi, Hidetoshi ; Sudo, Tomoya ; Sugimachi, Keishi ; Suzuki, Akira ; Wakabayashi, Go ; Mori, Masaki ; Mimori, Koshi. / Clinical significance of PICT1 in patients of hepatocellular carcinoma with wild-type TP53. In: Annals of Surgical Oncology. 2013 ; Vol. 20, No. 3 SUPPL. pp. S537-S544.
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abstract = "Background. TP53 is one of the most widely known cancer suppressor genes. Mutations in TP53 are ubiquitously observed in almost all cancers. Incidences of mutations range from *15-70 {\%} in patients with hepatocellular carcinoma (HCC). Moreover, patients with mutated TP53 have poorer prognoses than those with wildtype TP53; therefore, it would be beneficial to predict the prognosis of HCC patients with wild-type TP53. We previously reported that PICT1, coding a nucleolus protein, regulates TP53 through indirect association. Methods. In this study, we examined PICT1 expression levels and the status of TP53 in 51 primary HCC tissues in order to determine the clinical significance of PICT1 expression and the function of PICT1 in HCC cells. Results. We detected 6 mutations in the 51 samples. In 45 patients with wild-type TP53, those with high PICT1 expression (n = 11) had poorer prognoses than those with low PICT1 expression (n = 34), and there were no significant associations with other clinicopathological factors. According to gene set enrichment analysis, PICT1 expression was inversely correlated with the gene set of TP53. In vitro assays indicated that suppression of PICT1 expression caused an increase in TP53 expression, reduction in cell proliferation, and arrest at the G1 phase of the cell cycle in HCC cells expressing wild-type TP53. Conclusions. PICT1 should be a useful prognosticmarker in HCC patients having wild-type TP53. Furthermore, PICT1 may become a promising therapeutic target because of its ability to increase the expression and activation of TP53.",
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T1 - Clinical significance of PICT1 in patients of hepatocellular carcinoma with wild-type TP53

AU - Ishibashi, Masahisa

AU - Kogo, Ryunosuke

AU - Shibata, Kohei

AU - Ueo, Hiroki

AU - Uchi, Ryutaro

AU - Matsumura, Tae

AU - Takano, Yuki

AU - Sawada, Genta

AU - Takahashi, Yusuke

AU - Mima, Kousuke

AU - Kurashige, Junji

AU - Akiyoshi, Sayuri

AU - Iwaya, Takeshi

AU - Eguchi, Hidetoshi

AU - Sudo, Tomoya

AU - Sugimachi, Keishi

AU - Suzuki, Akira

AU - Wakabayashi, Go

AU - Mori, Masaki

AU - Mimori, Koshi

PY - 2013/3/27

Y1 - 2013/3/27

N2 - Background. TP53 is one of the most widely known cancer suppressor genes. Mutations in TP53 are ubiquitously observed in almost all cancers. Incidences of mutations range from *15-70 % in patients with hepatocellular carcinoma (HCC). Moreover, patients with mutated TP53 have poorer prognoses than those with wildtype TP53; therefore, it would be beneficial to predict the prognosis of HCC patients with wild-type TP53. We previously reported that PICT1, coding a nucleolus protein, regulates TP53 through indirect association. Methods. In this study, we examined PICT1 expression levels and the status of TP53 in 51 primary HCC tissues in order to determine the clinical significance of PICT1 expression and the function of PICT1 in HCC cells. Results. We detected 6 mutations in the 51 samples. In 45 patients with wild-type TP53, those with high PICT1 expression (n = 11) had poorer prognoses than those with low PICT1 expression (n = 34), and there were no significant associations with other clinicopathological factors. According to gene set enrichment analysis, PICT1 expression was inversely correlated with the gene set of TP53. In vitro assays indicated that suppression of PICT1 expression caused an increase in TP53 expression, reduction in cell proliferation, and arrest at the G1 phase of the cell cycle in HCC cells expressing wild-type TP53. Conclusions. PICT1 should be a useful prognosticmarker in HCC patients having wild-type TP53. Furthermore, PICT1 may become a promising therapeutic target because of its ability to increase the expression and activation of TP53.

AB - Background. TP53 is one of the most widely known cancer suppressor genes. Mutations in TP53 are ubiquitously observed in almost all cancers. Incidences of mutations range from *15-70 % in patients with hepatocellular carcinoma (HCC). Moreover, patients with mutated TP53 have poorer prognoses than those with wildtype TP53; therefore, it would be beneficial to predict the prognosis of HCC patients with wild-type TP53. We previously reported that PICT1, coding a nucleolus protein, regulates TP53 through indirect association. Methods. In this study, we examined PICT1 expression levels and the status of TP53 in 51 primary HCC tissues in order to determine the clinical significance of PICT1 expression and the function of PICT1 in HCC cells. Results. We detected 6 mutations in the 51 samples. In 45 patients with wild-type TP53, those with high PICT1 expression (n = 11) had poorer prognoses than those with low PICT1 expression (n = 34), and there were no significant associations with other clinicopathological factors. According to gene set enrichment analysis, PICT1 expression was inversely correlated with the gene set of TP53. In vitro assays indicated that suppression of PICT1 expression caused an increase in TP53 expression, reduction in cell proliferation, and arrest at the G1 phase of the cell cycle in HCC cells expressing wild-type TP53. Conclusions. PICT1 should be a useful prognosticmarker in HCC patients having wild-type TP53. Furthermore, PICT1 may become a promising therapeutic target because of its ability to increase the expression and activation of TP53.

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