PI3K pathway and Bcl-2 family. Clinicopathological features in prostate cancer

被引:24
作者
Torrealba, Norelia [1 ]
Rodriguez-Berriguete, Gonzalo [1 ]
Fraile, Benito [1 ]
Olmedilla, Gabriel [2 ]
Martinez-Onsurbe, Pilar [2 ]
Sanchez-Chapado, Manuel [3 ]
Paniagua, Ricardo [1 ]
Royuela, Mar [1 ]
机构
[1] Univ Alcala, Dept Biomed & Biotechnol, Alcala De Henares, Spain
[2] Univ Alcala, Dept Pathol, Alcala De Henares, Spain
[3] Principe Asturias Hosp, Dept Urol, Alcala De Henares, Spain
关键词
PI3K; AKT; mTOR; cancer prostate; Bcl-2; family; PI3K/AKT/MTOR PATHWAY; BIOCHEMICAL RECURRENCE; RADICAL PROSTATECTOMY; SIGNALING PATHWAYS; E-CADHERIN; AKT; EXPRESSION; PROGRESSION; PROMOTES; SURVIVAL;
D O I
10.1080/13685538.2018.1424130
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathways and Bcl-2 family play a central role in prostate cancer (PC). The aim was to determine influence in the biochemical progression in PC. To evaluate the association between clinic pathological and immunohistochemical variables, Spearman's test was performed. Log-rank test and Kaplan-Meier curves were used for survival comparisons. To explore the correlation of the studied immunohistochemical parameters and the established prognostic variables with biochemical progression, univariate and multivariate Cox proportional Hazard regression analyses were performed. Spearman analysis showed correlation between stroma expression and tumor expression of PI3K with biochemical progression (p=.009, p=.004), respectively, and tumor immunohistochemical score with biochemical progression (p=.051). In the multivariate Cox regression model, only PI3K was retained as independent predictors of biochemical progression. In stroma expression, PI3K is (HR 0.172, 95% CI 0.065-0.452, p=.000); tumor expression, PI3K is (HR 0.087, 95% CI 0.026-0.293, p=.000), and tumor immunohistochemical score (HR 0.382, 95% CI 0.209-0.697 p=.002). Our results suggest a role for prostatic expression of PI3K was prognostic markers for PC. PI3K/AKT/mTOR and Bcl-2 family are becoming an important therapeutic target and predictive biomarkers of onset and progression of PC.
引用
收藏
页码:211 / 222
页数:12
相关论文
共 54 条
  • [1] Phosphatidylinositol 3-kinase (PI3K) inhibitors as cancer therapeutics
    Akinleye, Akintunde
    Avvaru, Parthu
    Furqan, Muhammad
    Song, Yongping
    Liu, Delong
    [J]. JOURNAL OF HEMATOLOGY & ONCOLOGY, 2013, 6
  • [2] American Cancer Society, 2016, CANC FACTS FIGURES 2
  • [3] High levels of phosphorylated form of Akt-1 in prostate cancer and non-neoplastic prostate tissues are strong predictors of biochemical recurrence
    Ayala, G
    Thompson, T
    Yang, G
    Frolov, A
    Li, RL
    Scardino, P
    Ohori, M
    Wheeler, T
    Harper, W
    [J]. CLINICAL CANCER RESEARCH, 2004, 10 (19) : 6572 - 6578
  • [4] PI3K/AKT pathway regulates E-cadherin and Desmoglein 2 in aggressive prostate cancer
    Barber, Alison G.
    Castillo-Martin, Mireia
    Bonal, Dennis M.
    Jia, Angela J.
    Rybicki, Benjamin A.
    Christiano, Angela M.
    Cordon-Cardo, Carlos
    [J]. CANCER MEDICINE, 2015, 4 (08): : 1258 - 1271
  • [5] Can p53, Ki-67 and bcl-2 predict biochemical failure after radical prostatectomy?
    Baseskioglu, B.
    Akdogan, B.
    Baydar, D. E.
    Ozen, H.
    [J]. INDIAN JOURNAL OF UROLOGY, 2010, 26 (02) : 206 - 212
  • [6] Determining risk of biochemical recurrence in prostate cancer by immunohistochemical detection of PTEN expression end Akt activation
    Bedolla, Roble
    Prihoda, Thomas J.
    Kreisberg, Jeffrey I.
    Malik, Shazli N.
    Krishnegowda, Naveen K.
    Troyer, Dean A.
    Ghosh, Paramita M.
    [J]. CLINICAL CANCER RESEARCH, 2007, 13 (13) : 3860 - 3867
  • [7] Molecular Pathways: Mitochondrial Reprogramming in Tumor Progression and Therapy
    Caino, M. Cecilia
    Altieri, Dario C.
    [J]. CLINICAL CANCER RESEARCH, 2016, 22 (03) : 540 - 545
  • [8] The phosphoinositide 3-kinase pathway
    Cantley, LC
    [J]. SCIENCE, 2002, 296 (5573) : 1655 - 1657
  • [9] The PI3K/Akt/mTOR pathway in ovarian cancer: therapeutic opportunities and challenges
    Cheaib, Bianca
    Auguste, Aurelie
    Leary, Alexandra
    [J]. CHINESE JOURNAL OF CANCER, 2015, 34 (01) : 4 - 16
  • [10] How do BCL-2 proteins induce mitochondrial outer membrane permeabilization?
    Chipuk, Jerry E.
    Green, Douglas R.
    [J]. TRENDS IN CELL BIOLOGY, 2008, 18 (04) : 157 - 164