Khine Aye Aye, Huang Hsuan-Shun, Chen Pao-Chu, Hsu Chun-Shuo, Chen Ying-Hsi, Chu Sung-Chao, Chu Tang-Yuan
Center for Prevention and Therapy of Gynecological Cancers, Department of Research, Hualien Tzu Chi Hospital, Hualien 97004, Taiwan.
Department of Obstetrics & Gynecology, Hualien Tzu Chi Hospital, Hualien 97004, Taiwan.
Diagnostics (Basel). 2025 Aug 6;15(15):1975. doi: 10.3390/diagnostics15151975.
: The detection of ovarian cancer remains challenging due to the lack of reliable serum biomarkers that reflect malignant transformation rather than mere tumor presence. We developed a novel biotest using an immortalized human fallopian tube epithelial cell line (TY), which exhibits anchorage-independent growth (AIG) in response to cancer-associated serum factors. : Sera from ovarian and breast cancer patients, non-cancer controls, and ID8 ovarian cancer-bearing mice were tested for AIG-promoting activity in TY cells. : TY cells (passage 96) effectively distinguished cancer sera from controls (68.50 ± 2.12 vs. 17.50 ± 3.54 colonies, < 0.01) and correlated with serum CA125 levels ( = 0.73, = 0.03) in ovarian cancer patients. Receiver operating characteristic (ROC) analysis showed high diagnostic accuracy (AUC = 0.85, cutoff: 23.75 colonies). The AIG-promoting activity was mediated by HGF/c-MET and IGF/IGF-1R signaling, as inhibition of these pathways reduced phosphorylation and AIG. In an ID8 mouse ovarian cancer model, TY-AIG colonies strongly correlated with tumor burden ( = 0.95, < 0.01). : Our findings demonstrate that the TY cell-based AIG assay is a sensitive and specific biotest for detecting ovarian cancer and potentially other malignancies, leveraging the fundamental hallmark of malignant transformation.
由于缺乏反映恶性转化而非仅仅肿瘤存在的可靠血清生物标志物，卵巢癌的检测仍然具有挑战性。我们开发了一种新型生物检测方法，使用永生化的人输卵管上皮细胞系（TY），该细胞系对癌症相关血清因子表现出不依赖贴壁生长（AIG）。对卵巢癌和乳腺癌患者、非癌症对照以及荷ID8卵巢癌小鼠的血清进行了TY细胞中AIG促进活性的检测。TY细胞（第96代）能有效区分癌症血清与对照（68.50±2.12个集落对17.50±3.54个集落，P<0.01），并且与卵巢癌患者的血清CA125水平相关（r = 0.73，P = 0.03）。受试者工作特征（ROC）分析显示诊断准确性高（AUC = 0.85，临界值：23.75个集落）。AIG促进活性由HGF/c-MET和IGF/IGF-1R信号介导，因为抑制这些信号通路会降低磷酸化和AIG。在ID8小鼠卵巢癌模型中，TY-AIG集落与肿瘤负荷密切相关（r = 0.95，P<0.01）。我们的研究结果表明，基于TY细胞的AIG检测是一种敏感且特异的生物检测方法，可用于检测卵巢癌以及潜在的其他恶性肿瘤，利用了恶性转化的基本特征。
