PIK3R1 underexpression is an independent prognostic marker in breast cancer.
PIK3R1 underexpression is an independent prognostic marker in breast cancer.
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DOI：
10.1186/1471-2407-13-545
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发表时间：
2013-11-14
期刊：
影响因子：
3.8
通讯作者：
Bièche I
中科院分区：
文献类型：
--
作者：
Cizkova M;Vacher S;Meseure D;Trassard M;Susini A;Mlcuchova D;Callens C;Rouleau E;Spyratos F;Lidereau R;Bièche I
本研究的重点是PIK3CA和PIK3R1基因和其他PI3K通路相关基因在乳腺癌中的预后作用。在一系列458个乳腺癌样本中评估PIK3CA、PIK3R1和AKT1的突变和mRNA表达状态，以及参与PI3K通路的其他基因（EGFR、PDK1、PTEN、AKT2、AKT3、GOLPH3、WEE1、P70S6K）的表达状态。在151个样品（33.0%）中在外显子1、2、9和20中鉴定出PIK3CA突变。PIK3R1基因突变10例（2.2%），低表达283例（61.8%）。AKT1基因突变15例（3.3%），过表达116例（25.3%）。PIK3R1低表达倾向于与PIK3CA突变相互排斥（p = 0.00097）。PIK3CA突变与较好的无转移生存期相关，PIK3R1低表达与较差的无转移生存期相关（分别为p = 0.014和p = 0.00028）。通过结合PIK3CA突变和PIK3R1表达状态，确定了具有显著不同的无转移生存期的四个预后组（p = 0.00046）。在考克斯多变量回归分析中，在总人群（p = 0.0013）和乳腺癌亚组中证实了PIK3R1低表达的预后意义。PIK3CA突变和PIK3R1低表达对患者预后有相反的影响，可能成为乳腺癌有用的预后和预测因素。
The present study focused on the prognostic roles of PIK3CA and PIK3R1 genes and additional PI3K pathway-associated genes in breast cancer. 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. 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. PIK3CA mutations and PIK3R1 underexpression show opposite effects on patient outcome and could become useful prognostic and predictive factors in breast cancer.
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影响因子：
64.8
作者：
Ellis, Matthew J.;Ding, Li;Shen, Dong;Luo, Jingqin;Suman, Vera J.;Wallis, John W.;Van Tine, Brian A.;Hoog, Jeremy;Goiffon, Reece J.;Goldstein, Theodore C.;Ng, Sam;Lin, Li;Crowder, Robert;Snider, Jacqueline;Ballman, Karla;Weber, Jason;Chen, Ken;Koboldt, Daniel C.;Kandoth, Cyriac;Schierding, William S.;McMichael, Joshua F.;Miller, Christopher A.;Lu, Charles;Harris, Christopher C.;McLellan, Michael D.;Wendl, Michael C.;DeSchryver, Katherine;Allred, D. Craig;Esserman, Laura;Unzeitig, Gary;Margenthaler, Julie;Babiera, G. V.;Marcom, P. Kelly;Guenther, J. M.;Leitch, Marilyn;Hunt, Kelly;Olson, John;Tao, Yu;Maher, Christopher A.;Fulton, Lucinda L.;Fulton, Robert S.;Harrison, Michelle;Oberkfell, Ben;Du, Feiyu;Demeter, Ryan;Vickery, Tammi L.;Elhammali, Adnan;Piwnica-Worms, Helen;McDonald, Sandra;Watson, Mark;Dooling, David J.;Ota, David;Chang, Li-Wei;Bose, Ron;Ley, Timothy J.;Piwnica-Worms, David;Stuart, Joshua M.;Wilson, Richard K.;Mardis, Elaine R.
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影响因子：
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影响因子：
64.8
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