Biology and Medical Research Unit, The National Center for Energy and Nuclear Science and Technology, Rabat, Morocco.
Rabat Medical and Pharmacy School, Mohammed V University in Rabat, Rabat, Morocco.
Pan Afr Med J. 2022 Jan 20;41:59. doi: 10.11604/pamj.2022.41.59.31383. eCollection 2022.
in cancer cells, activating mutations in PIK3CA and AKT1 genes, major players of PI3K-AKT-mTOR signalling pathway, are widely reported in many cancers and present attractive targets for the identification of new therapeutics and better cancer management. The present study was planned to evaluate the mutational status of PIK3CA and AKT1 genes in bladder cancer patients and to assess the association between these mutations and patients´ clinico-pathological features.
in this prospective study, bladder cancer biopsies and matched urine sediments samples were collected form 70 patients. Mutations were assessed by deoxyribonucleic acid (DNA) sequencing and correlation with clinico-pathological data was performed using SPSS software.
AKT1 alterations were poorly detected. Only one patient with pT1 stage and high-grade tumour carried the E17K mutation. In PIK3CA exon 9, 2 point mutations, E545K and Q546E, and a SNP (E547E) were reported, whereas in exon 20, 2 point mutations (L989V and H1047R) and 2 SNPs (I1022I and T1025T) were detected. PIK3CA mutations were mainly observed in early stages and high-grade tumours. Statistical analysis showed no significant association between the studied AKT1 and PIK3CA mutations and patients´ clinico-pathological parameters (p > 0.05). Detection of these mutations in voided urine samples showed a high specificity (100%) for both genes and a moderate sensitivity: 100% for AKT1 and 66.7% for PIK3CA genes.
this study shows clearly that mutations in AKT1 and PIK3CA are rare events and could not be considered as valuable biomarkers for bladder cancer management.
在癌症细胞中，PI3K-AKT-mTOR 信号通路的主要参与者 PIK3CA 和 AKT1 基因的激活突变在许多癌症中广泛报道，是发现新的治疗方法和更好的癌症管理的有吸引力的目标。本研究旨在评估膀胱癌患者 PIK3CA 和 AKT1 基因的突变状态，并评估这些突变与患者临床病理特征之间的关系。
在这项前瞻性研究中，收集了 70 名患者的膀胱癌活检和配对的尿液沉淀物样本。通过脱氧核糖核酸 (DNA) 测序评估突变，并使用 SPSS 软件评估与临床病理数据的相关性。
AKT1 改变的检出率较低。只有一名 T1 期和高级别肿瘤患者携带 E17K 突变。在 PIK3CA 外显子 9 中，报告了 2 个点突变，E545K 和 Q546E，以及一个 SNP (E547E)，而在外显子 20 中，检测到 2 个点突变 (L989V 和 H1047R) 和 2 个 SNP (I1022I 和 T1025T)。PIK3CA 突变主要发生在早期和高级别肿瘤中。统计分析显示，研究的 AKT1 和 PIK3CA 突变与患者的临床病理参数之间无显著相关性 (p > 0.05)。在尿液样本中检测到这些突变，对两个基因均具有高特异性 (100%)，而敏感性适中：AKT1 为 100%，PIK3CA 为 66.7%。
本研究清楚地表明，AKT1 和 PIK3CA 突变是罕见事件，不能作为膀胱癌管理的有价值的生物标志物。
