Sefrioui David, Vermeulin Thomas, Blanchard France, Chapusot Caroline, Beaussire Ludivine, Armengol-Debeir Laura, Sesboué Richard, Gangloff Alice, Hebbar Mohamed, Copin Marie-Christine, Houivet Estelle, Schwarz Lilian, Clatot Florian, Tuech Jean-Jacques, Bénichou Jacques, Martin Laurent, Bouvier Anne-Marie, Sabourin Jean-Christophe, Sarafan-Vasseur Nasrin, Frébourg Thierry, Lepage Côme, Michel Pierre, Di Fiore Frédéric
Digestive Oncology Unit, Department of Hepato-Gastroenterology, Rouen University Hospital, Rouen, France.
Inserm U1079, University of Rouen, Institute for Biomedical Research and Innovation, Rouen, France.
Int J Cancer. 2017 Apr 1;140(7):1653-1661. doi: 10.1002/ijc.30584.
We conducted a prospective study to assess the prognostic impact of selected copy number variations (CNVs) in Stage II-III microsatellite stable (MSS) colon cancer. A total of 401 patients were included from 01/2004 to 01/2009. The CNVs in 8 selected target genes, DCC/18q, EGFR/7p, TP53/17p, BLK/8p, MYC/8q, APC/5q, ERBB2/17q and STK6/20q, were detected using a quantitative multiplex polymerase chain reaction of short fluorescent fragment (QMPSF) method. The primary end-point was the impact of the CNVs on the 4-year disease-free survival (DFS). The recurrence rate at 4 years was 20.9%, corresponding to 14% Stage II patients versus 31% Stage III patients (p < 0.0001). The 4-year DFS was significantly decreased in patients with a loss at DCC/18q (p = 0.012) and a gain at ERBB2/17q (p = 0.041). The multivariate analysis demonstrated that Stage III, a loss at DCC/18q and a gain at ERBB2/17q were independent factors associated with DFS. A combination of DCC/18q and ERBB2/17q was also associated with relapse, with the hazard ratio increasing from 1 to 2.4 (95% confidence interval (CI), 1.5-4.1) and 3.1 (95% CI, 1.2-8.4) in the presence of 0, 1 or 2 alterations, respectively (p = 0.0013). CNVs in DCC/18q and ERBB2/17q are significantly associated with DFS in Stage II-III MSS colon cancer.
我们开展了一项前瞻性研究，以评估特定拷贝数变异（CNV）对II-III期微卫星稳定（MSS）结肠癌预后的影响。2004年1月至2009年1月期间共纳入了401例患者。采用短荧光片段定量多重聚合酶链反应（QMPSF）方法检测8个选定靶基因（DCC/18q、EGFR/7p、TP53/17p、BLK/8p、MYC/8q、APC/5q、ERBB2/17q和STK6/20q）中的CNV。主要终点是CNV对4年无病生存期（DFS）的影响。4年复发率为20.9%，II期患者为14%，III期患者为31%（p < 0.0001）。DCC/18q缺失（p = 0.012）和ERBB2/17q扩增（p = 0.041）的患者4年DFS显著降低。多变量分析表明，III期、DCC/18q缺失和ERBB2/17q扩增是与DFS相关的独立因素。DCC/18q和ERBB2/17q联合也与复发相关，分别存在0、1或2种改变时，风险比从1增加到2.4（95%置信区间（CI），1.5 - 4.1）和3.1（95%CI，1.2 - 8.4）（p = 0.0013）。DCC/18q和ERBB2/17q中的CNV与II-III期MSS结肠癌的DFS显著相关。
