目的:IKAROS家族锌指3(IKZF3)是涉及不同恶性肿瘤的癌基因,特别是在淋巴细胞的发育和恶性进展中。然而,IKZF3在胃癌(GC)中的扩增和临床意义仍未被探索。
方法:我们使用组织微阵列(TMA)和荧光原位杂交(FISH)测定法检测了404个GC中IKZF3的扩增状态和HER2的扩增状态。
结果:在所有GC患者中检测到6.9%(28/404)的IKZF3扩增,肠型胃癌(IGC)发病率较高(11.22%,22/196)与其他类型(2.88%,6/208)。在所有GC患者的16.09%(65/404)中发现HER2扩增,IGC中的比率较高(20.92%,41/196)与其他类型(11.54%,24/208)。在8.16%(16/196)的IGC患者和2.40%(5/208)的其他类型患者中检测到IKZF3和HER2的共扩增。IKZF3扩增与IGC(P=0.001)和HER2扩增(P=0.0001)显著相关。IKZF3扩增显示GC患者的无病生存期(DFS)(P=0.014)和总生存期(OS)(P=0.018)显著恶化。特别是在IGC中(DFS:P<0.001;OS:P<0.001),而不是其他类型。Cox回归分析显示IKZF3扩增是所有GCs(P=0.006,P=0.004)和IGC患者的独立不良预后因素,无论I-II或III-IV阶段(分别为P=0.007,P=0.004)。另一方面,HER2扩增与IGC患者DFS(P=0.008)和OS(P=0.01)显著相关。但并非在所有GC和多变量分析中。在HER2扩增的患者亚组中,那些也表现出IKZF3扩增的患者显示出潜在的较差预后(分别为P=0.08,P=0.11).
结论:在少数GC患者中检测到IKZF3扩增,尤其是在IGC,是预后不良的独立指标。我们的研究,第一次,发现IKZF3对GC患者的预后价值优于HER2。
OBJECTIVE: IKAROS family zinc finger 3 (IKZF3) is an oncogene involved in different malignancies, particularly in the development and malignant progression of lymphocytes. However, IKZF3 amplification and clinical significance in gastric cancers (GCs) remain unexplored.
METHODS: We examined IKZF3 amplification status in 404 GCs with HER2 amplification status using tissue microarray (TMA) and fluorescence in situ hybridization (FISH) assays.
RESULTS: IKZF3 amplification was detected in 6.9% (28/404) of all GC patients, with higher rates in intestinal-type gastric cancer (IGC) (11.22%, 22/196) compared to other types (2.88%, 6/208). HER2 amplification was identified in 16.09% (65/404) of all GC patients, with higher rates in IGC (20.92%, 41/196) compared to other types (11.54%, 24/208). Co-amplification of IKZF3 and HER2 was detected in 8.16% (16/196) of IGC patients and in 2.40% (5/208) of other types. IKZF3 amplification showed significant correlation with IGC (P = 0.001) and HER2 amplification (P = 0.0001). IKZF3 amplification exhibited significantly worse disease-free survival (DFS) (P = 0.014) and overall survival (OS) (P = 0.018) in GC patients, particularly in IGC (DFS: P < 0.001; OS: P < 0.001), rather than other types. Cox regression analysis demonstrate IKZF3 amplification as an independent poor prognostic factor in all GCs (P = 0.006, P = 0.004 respectively) and in IGC patients, regardless of stages I-II or III-IV (P = 0.007, P = 0.004 respectively). On the other hand, HER2 amplification was significantly associated with worse DFS (P = 0.008) and OS (P = 0.01) in IGC patients, but not in all GCs and in multivariate analysis. Within the subset of patients with HER2 amplification, those also exhibiting IKZF3 amplification displayed potential poorer prognosis (P = 0.08, P = 0.11 respectively).
CONCLUSIONS: IKZF3 amplification was detected in minority of GC patients, especially in IGC, and was an independent indicator of poor prognosis. Our study, for the first time, found the prognostic value of IKZF3 was superior to HER2 for GC patients.