Sun Jia, Zhang Yingzi, Li Aijie, Yu Hao
Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong 271000, China.
Department of Hepatobiliary Surgery, The Affiliated Taian City Central Hospital of Qingdao University, Taian, Shandong 271000, China.
Int J Genomics. 2024 Mar 18;2024:6683202. doi: 10.1155/2024/6683202. eCollection 2024.
Epithelial ovarian cancer, primarily serous ovarian cancer (SOC), stands as a predominant cause of cancer-related mortality among women globally, emphasizing the urgent need for comprehensive research into its molecular underpinnings. Within this context, the dual-specificity tyrosine phosphorylation-regulated kinase 3 (DYRK3) has emerged as a potential key player with implications for prognosis and tumor progression.
This study conducted a meticulous retrospective analysis of 254 SOC cases from our medical center to unravel the prognostic significance of DYRK3. Survival analyses underscored DYRK3 as an independent adverse prognostic factor in SOC, with a hazard ratio of 2.60 (95% CI 1.67-4.07, < 0.001). Experimental investigations involved DYRK3 knockdown in serous ovarian cancer cell lines (CAOV3 and OVCAR-3) through a shRNA strategy, revealing substantial decreases in cell growth and invasion capabilities. Bioinformatics analyses further hinted at DYRK3's involvement in modulating the tumor immune microenvironment. In vivo experiments with DYRK3-knockdown cell lines validated these findings, demonstrating a notable restriction in the growth of ovarian cancer xenografts.
Our findings collectively illuminate DYRK3 as a pivotal tumor-promoting oncogene in SOC. Beyond its adverse prognostic implications, DYRK3 knockdown exhibited promising therapeutic potential by impeding cancer progression and potentially influencing the tumor immune microenvironment.
This study establishes a compelling foundation for further research into DYRK3's intricate role and therapeutic potential in ovarian cancer treatment. As we unravel the complexities surrounding DYRK3, our work not only contributes to the understanding of SOC pathogenesis but also unveils new prospects for targeted therapeutic interventions, holding promise for improved outcomes in ovarian cancer management.
上皮性卵巢癌,主要是浆液性卵巢癌(SOC),是全球女性癌症相关死亡的主要原因,这凸显了对其分子基础进行全面研究的迫切需求。在此背景下,双特异性酪氨酸磷酸化调节激酶3(DYRK3)已成为一个潜在的关键因素,对预后和肿瘤进展具有重要意义。
本研究对我们医疗中心的254例SOC病例进行了细致的回顾性分析,以阐明DYRK3的预后意义。生存分析强调DYRK3是SOC的独立不良预后因素,风险比为2.60(95%CI 1.67 - 4.07,P < 0.001)。实验研究通过shRNA策略在浆液性卵巢癌细胞系(CAOV3和OVCAR - 3)中敲低DYRK3,结果显示细胞生长和侵袭能力显著下降。生物信息学分析进一步表明DYRK3参与调节肿瘤免疫微环境。用敲低DYRK3的细胞系进行的体内实验验证了这些发现,表明卵巢癌异种移植瘤的生长受到显著限制。
我们的研究结果共同表明DYRK3是SOC中一个关键的促肿瘤癌基因。除了其不良预后意义外,敲低DYRK3通过阻碍癌症进展和潜在影响肿瘤免疫微环境显示出有前景的治疗潜力。
本研究为进一步研究DYRK3在卵巢癌治疗中的复杂作用和治疗潜力奠定了有力基础。随着我们揭示围绕DYRK3的复杂性,我们的工作不仅有助于理解SOC的发病机制,还揭示了靶向治疗干预的新前景,有望改善卵巢癌的治疗效果。