IKZF3 amplification predicts worse prognosis especially in intestinal-type gastric cancer.

IF 2.7 3区医学 Q3 ONCOLOGY

Journal of Cancer Research and Clinical Oncology Pub Date : 2024-07-25 DOI:10.1007/s00432-024-05868-2

Zhaomeng Cui, Huaiyu Liang, Rongkui Luo, Wen Huang, Wei Yuan, Lei Zhang, Lijuan Luan, Jieakesu Su, Jie Huang, Chen Xu, Yingyong Hou

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Abstract

Purpose: 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).

Conclusion: 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.

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IKZF3扩增预示着预后较差，尤其是在肠型胃癌中。

目的：IKAROS家族锌指3（IKZF3）是一种参与不同恶性肿瘤的癌基因，尤其是参与淋巴细胞的发育和恶性进展。然而，IKZF3在胃癌（GCs）中的扩增及临床意义仍未得到研究：方法：我们使用组织芯片（TMA）和荧光原位杂交（FISH）检测了404例HER2扩增的胃癌中IKZF3的扩增状态：在所有胃癌患者中，6.9%（28/404）的患者检测到IKZF3扩增，肠型胃癌（IGC）（11.22%，22/196）的IKZF3扩增率高于其他类型（2.88%，6/208）。在所有胃癌患者中，16.09%（65/404）的患者发现了 HER2 扩增，与其他类型（11.54%，24/208）相比，肠型胃癌（20.92%，41/196）中的 HER2 扩增率更高。8.16%的IGC患者（16/196）和2.40%的其他类型患者（5/208）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）有显著相关性。IKZF3扩增明显降低了GC患者的无病生存期（DFS）（P = 0.014）和总生存期（OS）（P = 0.018），尤其是IGC患者（DFS：P 结论：IKZF3扩增与GC患者的无病生存期（DFS）和总生存期（OS）密切相关：IKZF3扩增在少数GC患者中被检测到，尤其是在IGC患者中，并且是预后不良的独立指标。我们的研究首次发现，IKZF3 对 GC 患者的预后价值优于 HER2。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Cancer Research and Clinical Oncology 医学-肿瘤学

CiteScore

4.00

自引率

2.80%

发文量

577

审稿时长

2 months

期刊介绍： The "Journal of Cancer Research and Clinical Oncology" publishes significant and up-to-date articles within the fields of experimental and clinical oncology. The journal, which is chiefly devoted to Original papers, also includes Reviews as well as Editorials and Guest editorials on current, controversial topics. The section Letters to the editors provides a forum for a rapid exchange of comments and information concerning previously published papers and topics of current interest. Meeting reports provide current information on the latest results presented at important congresses. The following fields are covered: carcinogenesis - etiology, mechanisms; molecular biology; recent developments in tumor therapy; general diagnosis; laboratory diagnosis; diagnostic and experimental pathology; oncologic surgery; and epidemiology.