Mortan Laura F, Meelheim Brooke A, Garland Justin, Bohn Jacqueline A, Isingizwe Zitha Redempta, Benbrook Doris M
Gynecologic Oncology Section, Stephenson Cancer Center, Obstetrics and Gynecology Department, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States.
Pathology Department, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States.
Front Oncol. 2025 Jan 16;14:1524606. doi: 10.3389/fonc.2024.1524606. eCollection 2024.
BACKGROUND/OBJECTIVES: Patients with ovarian cancer commonly experience metastases and recurrences, which contribute to high mortality. Our objective was to better understand ovarian cancer metastasis and identify candidate biomarkers and drug targets for predicting and preventing ovarian cancer recurrence.
Transcripts of 770 cancer-associated genes were compared in cells collected from ascitic fluid versus resected tumors of an ES-2 orthotopic ovarian cancer mouse model. Associated cell types and pathways were explored with bioinformatics. FGF7 protein was measured using capillary-based immunoassays or ELISA in mouse and clinical specimens. Significances of differential gene expression and patient prognosis were determined by volcano plot and log-rank test, respectively.
Tumor transcriptomes exhibited higher endothelial cells, oxygenation, proteasome activity, and metabolism in comparison to ascites, but similar percentages of cancer-associated fibroblasts and immune cells. FGF7 mRNA was significantly higher in mouse tumors compared to ascites. FGF7 protein was significantly higher in tumors than in ascites in independent mouse models and clinical specimens. Serum FGF7 protein levels above the median of 25 patients with ovarian cancer were associated with worse progression-free and overall survival (p = 0.005 and 0.019, respectively) independent of patient and tumor characteristics.
In comparison to ascites, tumors exhibit different transcriptomic profiles that identify candidate biomarkers and drug targets for predicting and preventing recurrence. Among these, elevated tumoral FGF7 validated at the protein level and elevated serum FGF7 were significantly associated with worse patient survival. These results support further development of FGF7 receptor-targeted drugs and serum FGF7 to prevent and predict recurrence, respectively.
背景/目的：卵巢癌患者常发生转移和复发，这导致了高死亡率。我们的目的是更好地了解卵巢癌转移，并确定用于预测和预防卵巢癌复发的候选生物标志物和药物靶点。
在ES-2原位卵巢癌小鼠模型的腹水收集细胞与切除肿瘤细胞中，比较了770个癌症相关基因的转录本。通过生物信息学探索相关细胞类型和通路。使用基于毛细管的免疫测定法或ELISA在小鼠和临床标本中测量FGF7蛋白。分别通过火山图和对数秩检验确定差异基因表达的显著性和患者预后。
与腹水相比，肿瘤转录组显示出更高的内皮细胞、氧合、蛋白酶体活性和代谢，但癌症相关成纤维细胞和免疫细胞的百分比相似。与腹水相比，小鼠肿瘤中的FGF7 mRNA显著更高。在独立的小鼠模型和临床标本中，肿瘤中的FGF7蛋白显著高于腹水。25例卵巢癌患者血清FGF7蛋白水平高于中位数与无进展生存期和总生存期较差相关（分别为p = 0.005和0.019），与患者和肿瘤特征无关。
与腹水相比，肿瘤表现出不同的转录组谱，可确定用于预测和预防复发的候选生物标志物和药物靶点。其中，肿瘤FGF7在蛋白水平得到验证且血清FGF7升高与患者较差的生存率显著相关。这些结果支持分别进一步开发针对FGF7受体的药物和血清FGF7以预防和预测复发。
