PIK3R1 underexpression is an independent prognostic marker in breast cancer

被引：103

作者：

Cizkova, Magdalena ^{[1
,2
,3
,4
]}

Vacher, Sophie ^{[1
]}

Meseure, Didier ^{[5
]}

Trassard, Martine ^{[5
]}

Susini, Aurelie ^{[1
]}

Mlcuchova, Dana ^{[3
,4
]}

Callens, Celine ^{[1
]}

Rouleau, Etienne ^{[1
]}

Spyratos, Frederique ^{[1
]}

Lidereau, Rosette ^{[1
]}

Bieche, Ivan ^{[1
,6
]}

机构：

[1] Hosp Rene Huguenin, Inst Curie, Oncogenet Lab, F-92210 St Cloud, France

[2] Palacky Univ, Fac Med & Dent, Dept Oncol, CR-77147 Olomouc, Czech Republic

[3] Univ Hosp Olomouc, Olomouc, Czech Republic

[4] Palacky Univ, Fac Med & Dent, Inst Mol & Translat Med, Lab Expt Med, CR-77147 Olomouc, Czech Republic

[5] Hosp Rene Huguenin, Inst Curie, Dept Pathol, St Cloud, France

[6] Univ Paris 05, Fac Sci Pharmaceut & Biol, Sorbonne Paris Cite, INSERM UMR745, Paris, France

来源：

BMC CANCER | 2013年 / 13卷

关键词：

PIK3R1; PIK3CA; Breast cancer; Breast cancer subtypes; Signaling pathways; Prognostic value; CELL-CYCLE; PTEN LOSS; MUTATIONS; EXPRESSION; PROGRESSION; ACTIVATION; P110-ALPHA; P85-ALPHA; MECHANISM; CORRELATE;

D O I：

10.1186/1471-2407-13-545

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: The present study focused on the prognostic roles of PIK3CA and PIK3R1 genes and additional PI3K pathway-associated genes in breast cancer. Methods: The mutational and mRNA expression status of PIK3CA, PIK3R1 and AKT1, and expression status of other genes involved in the PI3K pathway (EGFR, PDK1, PTEN, AKT2, AKT3, GOLPH3, WEE1, P70S6K) were assessed in a series of 458 breast cancer samples. Results: PIK3CA mutations were identified in 151 samples (33.0%) in exons 1, 2, 9 and 20. PIK3R1 mutations were found in 10 samples (2.2%) and underexpression in 283 samples (61.8%). AKT1 mutations were found in 15 samples (3.3%) and overexpression in 116 samples (25.3%). PIK3R1 underexpression tended to mutual exclusivity with PIK3CA mutations (p = 0.00097). PIK3CA mutations were associated with better metastasis-free survival and PIK3R1 underexpression was associated with poorer metastasis-free survival (p = 0.014 and p = 0.00028, respectively). By combining PIK3CA mutation and PIK3R1 expression status, four prognostic groups were identified with significantly different metastasis-free survival (p = 0.00046). On Cox multivariate regression analysis, the prognostic significance of PIK3R1 underexpression was confirmed in the total population (p = 0.0013) and in breast cancer subgroups. Conclusions: PIK3CA mutations and PIK3R1 underexpression show opposite effects on patient outcome and could become useful prognostic and predictive factors in breast cancer.

引用

页数：15

共 39 条

[1] Cancer-specific mutations in PIK3CA are oncogenic in vivo [J].

Bader, AG ;

Kang, SY ;

Vogt, PK .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (05) :1475-1479

[2] Different prognostic roles of mutations in the helical and kinase domains of the PIK3CA gene in breast carcinomas [J].

Barbareschi, Mattia ;

Buttitta, Fiamma ;

Felicioni, Lara ;

Cotrupi, Sabrina ;

Barassi, Fabio ;

Del Grammastro, Maela ;

Ferro, Antonella ;

Palma, Paolo Dalla ;

Galligioni, Enzo ;

Marchetti, Antonio .

CLINICAL CANCER RESEARCH, 2007, 13 (20) :6064-6069

[3] Targeting the Phosphoinositide-3 (PI3) Kinase Pathway in Breast Cancer [J].

Baselga, Jose .

ONCOLOGIST, 2011, 16 :12-19

[4] Quantification of estrogen receptor α and β expression in sporadic breast cancer [J].

Bièche, I ;

Parfait, B ;

Laurendeau, I ;

Girault, I ;

Vidaud, M ;

Lidereau, R .

ONCOGENE, 2001, 20 (56) :8109-8115

[5]

Bièche I, 1999, CLIN CHEM, V45, P1148

[6]

Bossard C, 2005, ANTICANCER RES, V25, P4679

[7] The phosphatidyl inositol 3-kinase/AKT signaling pathway in breast cancer [J].

Castaneda, Carlos A. ;

Cortes-Funes, Hernan ;

Gomez, Henry L. ;

Ciruelos, Eva M. .

CANCER AND METASTASIS REVIEWS, 2010, 29 (04) :751-759

[8] High Frequency of PIK3R1 and PIK3R2 Mutations in Endometrial Cancer Elucidates a Novel Mechanism for Regulation of PTEN Protein Stability [J].

Cheung, Lydia W. T. ;

Hennessy, Bryan T. ;

Li, Jie ;

Yu, Shuangxing ;

Myers, Andrea P. ;

Djordjevic, Bojana ;

Lu, Yiling ;

Stemke-Hale, Katherine ;

Dyer, Mary D. ;

Zhang, Fan ;

Ju, Zhenlin ;

Cantley, Lewis C. ;

Scherer, Steven E. ;

Liang, Han ;

Lu, Karen H. ;

Broaddus, Russell R. ;

Mills, Gordon B. .

CANCER DISCOVERY, 2011, 1 (02) :170-185

[9] PIK3CA mutation impact on survival in breast cancer patients and in ERα, PR and ERBB2-based subgroups [J].

Cizkova, Magdalena ;

Susini, Aurelie ;

Vacher, Sophie ;

Cizeron-Clairac, Geraldine ;

Andrieu, Catherine ;

Driouch, Keltouma ;

Fourme, Emmanuelle ;

Lidereau, Rosette ;

Bieche, Ivan .

BREAST CANCER RESEARCH, 2012, 14 (01)

[10]

COX DR, 1972, J R STAT SOC B, V34, P187

← 1 2 3 4 →