PIK3CA mutations predict recurrence in localized microsatellite stable colon cancer.
PIK3CA mutations predict recurrence in localized microsatellite stable colon cancer.
复制标题
DOI：
10.1002/cam4.370
复制
发表时间：
2015-03
期刊：
影响因子：
4
通讯作者：
Laurent-Puig, Pierre
中科院分区：
文献类型：
--
作者：
Manceau, Gilles;Marisa, Laetitia;Boige, Valerie;Duval, Alex;Gaub, Marie-Pierre;Milano, Gerard;Selves, Janick;Olschwang, Sylviane;Jooste, Valerie;le Legrain, Miche;Lecorre, Delphine;Guenot, Dominique;Etienne-Grimaldi, Marie-Christine;Kirzin, Sylvain;Martin, Laurent;Lepage, Come;Bouvier, Anne-Marie;Laurent-Puig, Pierre
PIK3CA编码PI3Kα的p110α催化亚基，是结肠癌中最常见的癌基因之一，但其预后价值仍存在争议。很少有报告指出PIK3CA突变与存活率之间的关联，其结果也存在争议。在本研究中，我们旨在根据错配修复状态来阐明PIK3CA突变对I-III期CC预后的影响。对来自两个独立队列的826例根治性切除CC患者的新鲜冰冻组织样本进行微卫星不稳定性分析，并通过直接测序筛选PIK3CA外显子9和20的激活点突变。总体而言，693个肿瘤(84%)表现出微卫星稳定性(MSS)，113个样本(14%)携带PIK3CA突变。在回顾性训练队列中(n=433)，在单因素分析中，PIK3CA突变的MSS肿瘤患者(n=47)与PIK3CA野生型MSS肿瘤患者(n=319)相比，5年无复发间隔显著增加(94%vs.68%，对数列P=10.0)。多因素分析(HR=0.12；95%可信区间0.029-0.48；P=0.0027)。在前瞻性验证队列中(n=393)，PIK3CA突变在MSS肿瘤(n=327)中的有利预后影响得到确认(83%vs.67%，对数列P=100.04)。我们的研究表明，PIK3CA突变与MSS I-III期CC患者的良好预后相关。
PIK3CA, which encodes the p110α catalytic subunit of PI3Kα, is one of the most frequently altered oncogenes in colon cancer (CC), but its prognostic value is still a matter of debate. Few reports have addressed the association between PIK3CA mutations and survival and their results are controversial. In the present study, we aimed to clarify the prognostic impact of PIK3CA mutations in stage I–III CC according to mismatch repair status. Fresh frozen tissue samples from two independent cohorts with a total of 826 patients who underwent curative surgical resection of CC were analyzed for microsatellite instability and screened for activating point mutations in exon 9 and 20 of PIK3CA by direct sequencing. Overall, 693 tumors (84%) exhibited microsatellite stability (MSS) and 113 samples (14%) harbored PIK3CA mutation. In the retrospective training cohort (n = 433), patients with PIK3CA-mutated MSS tumors (n = 47) experienced a significant increased 5-year relapse-free interval compared with PIK3CA wild-type MSS tumors (n = 319) in univariate analysis (94% vs. 68%, Log-rank P = 0. 0003) and in multivariate analysis (HR = 0.12; 95% confidence interval, 0.029–0.48; P = 0.0027). In the prospective validation cohort (n = 393), the favorable prognostic impact of PIK3CA mutations in MSS tumors (n = 327) was confirmed (83% vs. 67%, Log-rank P = 0.04). Our study showed that PIK3CA mutations are associated with a good prognosis in patients with MSS stage I–III CC.
登录
查看更多内容
影响因子：
11.5
作者：
Day, Fiona L.;Jorissen, Robert N.;Sieber, Oliver M.
通讯作者：
Sieber, Oliver M.
影响因子：
14.9
作者：
Forbes SA;Bindal N;Bamford S;Cole C;Kok CY;Beare D;Jia M;Shepherd R;Leung K;Menzies A;Teague JW;Campbell PJ;Stratton MR;Futreal PA
通讯作者：
Futreal PA
影响因子：
11.2
作者：
Ikenoue, T;Kanai, F;Omata, M
通讯作者：
Omata, M
影响因子：
45.3
作者：
Gerard, Jean-Pierre;Conroy, Thierry;Bedenne, Laurent
通讯作者：
Bedenne, Laurent
影响因子：
8
作者：
Abubaker, J.;Bavi, P.;Al-Kuraya, K. S.
通讯作者：
Al-Kuraya, K. S.