Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Department of Pathology, Xiamen Branch of Zhongshan Hospital, Fudan University, Xiamen, 361015, Fujian, China.
J Cancer Res Clin Oncol. 2024 Jul 25;150(7):363. doi: 10.1007/s00432-024-05868-2.
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.
We examined IKZF3 amplification status in 404 GCs with HER2 amplification status using tissue microarray (TMA) and fluorescence in situ hybridization (FISH) assays.
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).
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.
IKAROS 家族锌指蛋白 3（IKZF3）是一种参与多种恶性肿瘤的癌基因，特别是在淋巴细胞的发生和恶性进展中。然而，IKZF3 扩增及其在胃癌（GC）中的临床意义仍未被探索。
我们使用组织微阵列（TMA）和荧光原位杂交（FISH）检测了 404 例 GC 患者的 IKZF3 扩增状态及其 HER2 扩增状态。
所有 GC 患者中 IKZF3 扩增的检出率为 6.9%（28/404），肠型胃癌（IGC）中 IKZF3 扩增的检出率（11.22%，22/196）高于其他类型（2.88%，6/208）。所有 GC 患者中 HER2 扩增的检出率为 16.09%（65/404），IGC 中 HER2 扩增的检出率（20.92%，41/196）高于其他类型（11.54%，24/208）。IGC 患者中有 8.16%（16/196）和其他类型中有 2.40%（5/208）同时存在 IKZF3 和 HER2 扩增。IKZF3 扩增与 IGC（P=0.001）和 HER2 扩增（P=0.0001）显著相关。在 GC 患者中，IKZF3 扩增与无病生存（DFS）（P=0.014）和总生存（OS）（P=0.018）显著相关，尤其是在 IGC 患者中（DFS：P<0.001；OS：P<0.001），而非其他类型。Cox 回归分析显示，在所有 GC 患者（P=0.006，P=0.004）和 IGC 患者中（无论分期为 I-II 期还是 III-IV 期，P=0.007，P=0.004），IKZF3 扩增均为独立的不良预后因素。另一方面，HER2 扩增与 IGC 患者的 DFS（P=0.008）和 OS（P=0.01）显著相关，但在所有 GC 患者和多变量分析中不相关。在 HER2 扩增的患者亚组中，同时存在 IKZF3 扩增的患者显示出潜在的更差预后（P=0.08，P=0.11）。
IKZF3 扩增在少数 GC 患者中检出，尤其是在 IGC 中，是独立的不良预后指标。本研究首次发现，IKZF3 的预后价值优于 HER2 对 GC 患者。
