Department of Urology, Tekirdag Namık Kemal University Medical School, Tekirdag.
Department of Biochemistry, Balıkesir University Medical School, Balıkesir.
Arch Ital Urol Androl. 2021 Jun 28;93(2):148-152. doi: 10.4081/aiua.2021.2.148.
It has been shown that the dysregulation of tyrosine kinase Axl receptor and its ligand growth arrest-specific gene (Gas6) are associated with poor prognosis in various types of tumors but there is not enough study about their importance in bladder cancer (BC). We evaluated the relation of Gas6 gene expression and tyrosine- kinase Axl and Sky (Tyro 3) receptors with tumor stage and grade in patients with BC.
The study group consists of 55 patients whose transurethral resection of bladder (TUR-B) has been performed due to BC and the control group consists of 12 patients with normal bladder mucosa. In tissues mRNAs of Gas6, Axl, and Sky receptors were examined by quantitative (Real-Time) PCR (qPCR). Protein expression was measured by immunohistochemistry. Plasma Gas6 protein levels were compared with control group by ELISA method.
Patients with BC were grouped as Ta low (n=17), Ta high (n=5), T1 low (n=9), T1 high (n=8) and T2 (n=16) according to their TUR-B pathologies. The qPCR analysis showed that the expression of Gas6 gene and Axl receptor is higher in the tumor-positive group and the immune-histochemical showed that the bladder samples of the tumor-positive group stained significantly positive. When the patients are grouped according to the TUR-B pathologies, a statistical significant difference was observed among groups in the qPCR analysis ratios of Gas6 gene and Axl receptor by (p < 0.05) but no significance was found for Sky receptor (p > 0.05). When Gas6 protein levels in plasma samples were compared by ELISA method, a statistical significance was determined among groups (p = 0.001).
Our findings indicate that mRNAs of Gas6 and Axl receptor are closely related to tumor stage and grade in patients with BC. Further studies are needed for understanding the role of Gas6 and its receptors on the neoplastic transformation in terms of novel biomarkers and potential therapeutic targets.
已证实，酪氨酸激酶 Axl 受体及其配体生长停滞特异性基因（Gas6）的失调与各种类型肿瘤的不良预后相关，但关于其在膀胱癌（BC）中的重要性的研究还不够。我们评估了 Gas6 基因表达与酪氨酸激酶 Axl 和 Sky（Tyro 3）受体与 BC 患者肿瘤分期和分级的关系。
研究组包括 55 名因 BC 而行经尿道膀胱肿瘤切除术（TUR-B）的患者，对照组包括 12 名正常膀胱黏膜患者。通过定量（实时）PCR（qPCR）检测组织中 Gas6、Axl 和 Sky 受体的 mRNAs。通过免疫组织化学法测量蛋白表达。通过 ELISA 法比较血浆 Gas6 蛋白水平与对照组。
根据 TUR-B 病理，BC 患者被分为 Ta 低（n=17）、Ta 高（n=5）、T1 低（n=9）、T1 高（n=8）和 T2（n=16）。qPCR 分析显示，肿瘤阳性组 Gas6 基因和 Axl 受体的表达较高，免疫组化显示肿瘤阳性组膀胱样本染色明显阳性。当根据 TUR-B 病理对患者进行分组时，qPCR 分析显示 Gas6 基因和 Axl 受体的比率在组间存在统计学显著差异（p<0.05），但 Sky 受体无差异（p>0.05）。通过 ELISA 法比较血浆样本中的 Gas6 蛋白水平时，组间存在统计学差异（p=0.001）。
我们的研究结果表明，Gas6 和 Axl 受体的 mRNAs 与 BC 患者的肿瘤分期和分级密切相关。需要进一步的研究来了解 Gas6 及其受体在肿瘤转化中的作用，作为新的生物标志物和潜在的治疗靶点。
