Clinical Significance of PICT1 in Patients of Hepatocellular Carcinoma with Wild-Type TP53

被引:8
|
作者
Ishibashi, Masahisa [1 ,2 ]
Kogo, Ryunosuke [1 ]
Shibata, Kohei [1 ]
Ueo, Hiroki [1 ]
Uchi, Ryutaro [1 ]
Matsumura, Tae [1 ]
Takano, Yuki [1 ]
Sawada, Genta [1 ]
Takahashi, Yusuke [1 ]
Mima, Kousuke [1 ]
Kurashige, Junji [1 ]
Akiyoshi, Sayuri [1 ]
Iwaya, Takeshi [1 ,2 ]
Eguchi, Hidetoshi [1 ]
Sudo, Tomoya [1 ]
Sugimachi, Keishi [1 ]
Suzuki, Akira [3 ]
Wakabayashi, Go [2 ]
Mori, Masaki [4 ]
Mimori, Koshi [1 ]
机构
[1] Kyushu Univ, Beppu Hosp, Dept Surg, Beppu, Oita, Japan
[2] Iwate Med Univ, Dept Surg, Morioka, Iwate 020, Japan
[3] Kyushu Univ, Med Inst Bioregulat, Div Canc Genet, Fukuoka 812, Japan
[4] Osaka Univ, Dept Surg Gastroenterol, Suita, Osaka, Japan
基金
日本学术振兴会; 日本科学技术振兴机构;
关键词
TUMOR-SUPPRESSOR CANDIDATE; P53; MUTATION; PROGNOSTIC INDICATOR; POOR-PROGNOSIS; PROTEIN ACCUMULATION; MDM2-P53; PATHWAY; CANCER; EXPRESSION; GENE; OVEREXPRESSION;
D O I
10.1245/s10434-013-2958-x
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 similar to 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 G(1) phase of the cell cycle in HCC cells expressing wild-type TP53. Conclusions. PICT1 should be a useful prognostic marker 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.
引用
收藏
页码:S537 / S544
页数:8
相关论文
共 50 条
  • [21] Clinical Significance of PICT1/GLTSCR2 Expression in Gastric Cancer
    Uchi, R.
    Kogo, R.
    Ueo, H.
    Takano, Y.
    Matsumura, T.
    Ishibashi, M.
    Sudo, T.
    Sugimachi, K.
    Suzuki, A.
    Komune, S.
    Mimori, K.
    ANNALS OF SURGICAL ONCOLOGY, 2013, 20 : S132 - S133
  • [22] Complete loss of wild-type TP53 in a nontransformed human epithelial cell line is preceded by a phase during which a heterozygous TP53 mutant effectively outgrows the homozygous wild-type cells
    Villadsen, R
    Nielsen, KV
    Bolund, L
    Briand, P
    CANCER GENETICS AND CYTOGENETICS, 2000, 116 (01) : 28 - 34
  • [23] Clinical significance of TP53 mutation in myeloma
    Chng, W. J.
    Price-Troska, T.
    Gonzalez-Paz, N.
    Van Wier, S.
    Jacobus, S.
    Blood, E.
    Henderson, K.
    Oken, M.
    Van Ness, B.
    Greipp, P.
    Rajkumar, S. V.
    Fonseca, R.
    LEUKEMIA, 2007, 21 (03) : 582 - 584
  • [24] Clinical significance of TP53 mutation in myeloma
    W J Chng
    T Price-Troska
    N Gonzalez-Paz
    S Van Wier
    S Jacobus
    E Blood
    K Henderson
    M Oken
    B Van Ness
    P Greipp
    S V Rajkumar
    R Fonseca
    Leukemia, 2007, 21 : 582 - 584
  • [25] KEVETRIN TARGETS TP53 WILD-TYPE AND MUTANT ACUTE MYELOID LEUKEMIA CELLS
    Napolitano, R.
    De Matteis, S.
    Carloni, S.
    Ghetti, M.
    Liverani, C.
    Bochicchio, M. T.
    di Rora, A. Ghelli Luserna
    Fontana, M. C.
    Padella, A.
    Mercatali, L.
    Menon, K.
    Musuraca, G.
    Martinelli, G.
    Simonetti, G.
    HAEMATOLOGICA, 2020, 105 : S88 - S89
  • [26] Chemokine Network and Overall Survival in TP53 Wild-Type and Mutant Ovarian Cancer
    Ignacio, Rosa Mistica C.
    Lee, Eun-Sook
    Wilson, Andrew J.
    Beeghly-Fadiel, Alicia
    Whalen, Margaret M.
    Son, Deok-Soo
    IMMUNE NETWORK, 2018, 18 (04)
  • [27] Depicting the role of TP53 in hepatocellular carcinoma progression
    Villanueva, Augusto
    Hoshida, Yujin
    JOURNAL OF HEPATOLOGY, 2011, 55 (03) : 724 - 725
  • [28] Association between TP53 R249S mutation and polymorphisms in TP53 intron 1 in hepatocellular carcinoma
    Ortiz-Cuaran, Sandra
    Cox, David
    Villar, Stephanie
    Friesen, Marlin D.
    Durand, Geoffroy
    Chabrier, Amelie
    Khuhaprema, Thiravud
    Sangrajrang, Suleeporn
    Ognjanovic, Simona
    Groopman, John D.
    Hainaut, Pierre
    Le Calvez-Kelm, Florence
    GENES CHROMOSOMES & CANCER, 2013, 52 (10): : 912 - 919
  • [29] MDM4 Overexpressed in Acute Myeloid Leukemia Patients with Complex Karyotype and Wild-Type TP53
    Li, Li
    Tan, Yanhong
    Chen, Xiuhua
    Xu, Zhifang
    Yang, Siyao
    Ren, Fanggang
    Guo, Haixiu
    Wang, Xiaojuan
    Chen, Yi
    Li, Guoxia
    Wang, Hongwei
    PLOS ONE, 2014, 9 (11):
  • [30] Variation characteristics and clinical significance of TP53 in patients with myeloid neoplasms
    Ma, Qiang
    Liu, Yan
    Zhao, Hong
    Guo, Yixian
    Sun, Wanling
    Hu, Ronghua
    HEMATOLOGY, 2024, 29 (01)