Rzepecka Iwona K, Tysarowski Andrzej, Konopka Bozena, Dansonka-Mieszkowska Agnieszka, Kupryjanczyk Jolanta
Cancer Molecular and Genetic Diagnostics Department, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland.
Department of Cancer Pathomorphology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland.
Cancers (Basel). 2025 Jan 15;17(2):269. doi: 10.3390/cancers17020269.
The phosphoinositide 3-kinase (PI3K) pathway is activated in multiple cancers. However, the significance of encoding the PI3K regulatory subunit, an inhibitor of the PI3K catalytic subunit encoded by , in ovarian cancer development is largely unknown.
Here, we investigated genomic alterations and gene expression by direct sequencing and qPCR methods in 197 ovarian cancers. The results were correlated with clinicopathological and molecular variables and patient outcomes.
In addition to mutations (3.5%) and allelic losses (28.4%), we observed a very high frequency of decreased mRNA levels in ovarian carcinomas (95.8%). Tumors with mutations mostly represented low-stage cancers of endometrioid and clear-cell type. Tumors with deletion and underexpression shared similar phenotypes of high-grade carcinomas ( = 0.003 and = 0.025, respectively). Allelic loss was also associated with advanced stages ( = 0.003) and high-grade serous histotypes ( = 0.004). The copy number correlated with mRNA levels ( = 0.009). mutations coexisted with mutations ( = 0.041), whereas deletion and underexpression were linked to amplification ( = 0.038 and = 0.033, respectively). Low expression diminished the probability of a complete response (OR 0.07, = 0.03) in patients treated with platinum-based regimens.
alterations may contribute to the development of ovarian cancers with different malignant potential and molecular changes. The high frequency of aberrations suggests their importance in PI3K pathway deregulation, and they may potentially serve as an alternative to markers for therapy with these pathway inhibitors.
磷酸肌醇3激酶（PI3K）通路在多种癌症中被激活。然而，编码PI3K调节亚基（由 编码的PI3K催化亚基的抑制剂）在卵巢癌发生中的意义在很大程度上尚不清楚。
在此，我们通过直接测序和qPCR方法研究了197例卵巢癌中的 基因组改变和基因表达。结果与临床病理和分子变量以及患者预后相关。
除了突变（3.5%）和等位基因缺失（28.4%）外，我们在卵巢癌中观察到 mRNA水平降低的频率非常高（95.8%）。有 突变的肿瘤大多为子宫内膜样和透明细胞型的低分期癌症。有 缺失和低表达的肿瘤具有高级别癌的相似表型（分别为P = 0.003和P = 0.025）。等位基因缺失也与晚期（P = 0.003）和高级别浆液性组织学类型（P = 0.004）相关。 拷贝数与mRNA水平相关（P = 0.009）。 突变与 突变共存（P = 0.041），而 缺失和低表达与 扩增相关（分别为P = 0.038和P = 0.033）。低 表达降低了接受铂类方案治疗的患者完全缓解的概率（OR 0.07，P = 0.03）。
改变可能有助于具有不同恶性潜能和分子变化的卵巢癌的发生。 畸变的高频率表明它们在PI3K通路失调中的重要性，并且它们可能潜在地作为这些通路抑制剂治疗的 标志物的替代物。
