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

研究成果: ジャーナルへの寄稿記事

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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.

元の言語英語
ページ(範囲)S537-S544
ジャーナルAnnals of Surgical Oncology
20
発行部数3 SUPPL.
DOI
出版物ステータス出版済み - 3 27 2013

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All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

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