TY - JOUR
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
N1 - Funding Information:
GRANT SUPPORT This work was supported in part by the following grants and foundations: CREST, Japan Science and Technology Agency; Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research, grant No. 20390360, 20591547, 20790960, 21591644, 21791295, 21791297, 215921014, and 21679006; the Funding Program for Next Generation World-Leading Researchers (LS094); New Energy and Industrial Technology Development Organization Technological Development for Chromosome Analysis; and a Grant-in-Aid from the Tokyo Biochemical Research Foundation.
PY - 2013
Y1 - 2013
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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U2 - 10.1245/s10434-013-2958-x
DO - 10.1245/s10434-013-2958-x
M3 - Article
C2 - 23532381
AN - SCOPUS:84892810099
SN - 1068-9265
VL - 20
SP - S537-S544
JO - Annals of Surgical Oncology
JF - Annals of Surgical Oncology
IS - 3 SUPPL.
ER -