Huynh Huong Thi Luu Kim, Lim Hendrick Gao-Min, Lee Yuan-Chii Gladys, Phan Thien-Vy, Vo Thanh-Hoa, Chen Chien-Hsin, Wu Alexander T H
International PhD Program for Translational Science, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
Int J Med Sci. 2025 Mar 19;22(8):1885-1904. doi: 10.7150/ijms.105193. eCollection 2025.
Pancreatic cancer (PC) is one of the most tremendously malignant cancers with a poor prognosis, especially when it advances to metastasis. Besides, PC patients have encountered resistance to recent therapeutic approaches. In recent work, we effectively determined ANKRD22 by re-analyzing RNA-seq datasets from cell lines and human tissues deriving from PC. We demonstrated that ANKRD22 expression was remarkably high in the PC group compared to the normal group at both gene expression and protein levels. ANKRD22 resulted in a worse overall survival (OS) rate of PC patients (HR = 1.7, p = 0.0082). Intriguingly, ANKRD22 was statistically highly expressed in the mutated KRAS group relative to the wildtype group (p < 0.05). Similarly, compared to the wildtype TP53, in the mutated TP53, ANKRD22 also significantly expressed (p < 0.05); their concurrent expression, ANKRD22 and KRAS; ANKRD22 and TP53 exacerbated the survival outcome relative to the co-expression of low ANKRD22 and unaltered genes (p < 0.001; HR > 2.6). We explored the potential pathways and biological processes ANKRD22 might not only contribute to promoting PC, including cell-cycle regulation, E2F1 targets, and apoptosis but also foster the dissemination of PC by involve in invasion and migration processes. In the investigation of drugs that might target ANKRD22, we figured out fostamatinib. Molecular docking and molecular dynamic simulation (MDs) techniques provided extensive insights into the binding mode of ANKRD22 and fostamatinib. ANKRD22 exhibited strong binding affinity (ΔG = -7.0 kcal/mol in molecular docking and ∆G = -38.66 ± 6.09 kcal/mol in MDs). Taken together, ANKRD22 could be a promising theragnostic target that might be inhibited by fostamatinib, thereby suppressing PC growth.
胰腺癌（PC）是最具恶性的癌症之一，预后较差，尤其是发展到转移阶段时。此外，PC患者对近期的治疗方法产生了耐药性。在最近的研究中，我们通过重新分析来自PC细胞系和人体组织的RNA测序数据集，有效地确定了ANKRD22。我们证明，在基因表达和蛋白质水平上，与正常组相比，PC组中ANKRD22的表达显著更高。ANKRD22导致PC患者的总生存率（OS）更差（HR = 1.7，p = 0.0082）。有趣的是，相对于野生型组，ANKRD22在KRAS突变组中在统计学上高表达（p < 0.05）。同样，与野生型TP53相比，在TP53突变型中，ANKRD22也显著表达（p < 0.05）；ANKRD22与KRAS的同时表达；ANKRD22与TP53相对于低ANKRD22与未改变基因的共表达加剧了生存结果（p < 0.001；HR > 2.6）。我们探索了ANKRD22可能不仅有助于促进PC的潜在途径和生物学过程，包括细胞周期调控、E2F1靶点和细胞凋亡，还通过参与侵袭和迁移过程促进PC的扩散。在对可能靶向ANKRD22的药物的研究中，我们找到了福斯替尼。分子对接和分子动力学模拟（MDs）技术为ANKRD22与福斯替尼的结合模式提供了广泛的见解。ANKRD22表现出很强的结合亲和力（分子对接中ΔG = -7.0 kcal/mol，MDs中∆G = -38.66 ± 6.09 kcal/mol）。综上所述，ANKRD22可能是一个有前景的治疗诊断靶点，可能被福斯替尼抑制，从而抑制PC的生长。
