β-连环蛋白和同源盒蛋白 2B（PHOX2B）在神经母细胞瘤患者中的表达；预测和预后价值。
The role of β-catenin and paired-like homeobox 2B (PHOX2B) expression in neuroblastoma patients; predictive and prognostic value.
机构信息
Clinical Pathology Department, National Cancer Institute, Cairo University, Cairo 11976, Egypt.
Medical Biochemistry and Molecular Biology, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo 11976, Egypt.
出版信息
Exp Mol Pathol. 2019 Oct;110:104272. doi: 10.1016/j.yexmp.2019.104272. Epub 2019 Jun 18.
BACKGROUND
The expression of β-catenin and paired-like homeobox 2B (PHOX2B) expression were assessed in Neuroblastoma (NB) patients as a diagnostic, prognostic and/or predictive markers.
METHODS
Bone marrow (BM) samples of 52 NB patients were assessed for the expression of β-catenin by immunohistochemistry (IHC), and PHOX2B by real time PCR (RT-PCR), compared to 12 healthy normal controls (NC). The data were correlated to the clinic-pathological features of the patients, response to treatment and disease relapse.
RESULTS
β-catenin was expressed in 40 (76.92%) patients (P < .001). While PHOX2B was expressed in 32/52 (61.5%) patients, with a fold change of 0.29 (0.01-40.0, P = .096). β-catenin expression associated significantly with advanced tumor stage, high risk, positive results by MIBG and bone scan (P = .002, P < .001, P = .006, P = .013; respectively). Also it associated significantly with synaptophysin expression in the BM biopsy (P < .001), with a significant concordance (K = 0.519, P < .001). The expression of β-catenin associated significantly with PHOX2B gene expression [28/32 (87.5%), P = .04], and its fold change (P = .027), with a significant measure of agreement (K = 0.297, P = .022). The fold change of PHOX2B gene expression associated significantly with the high risk of the patients (P = .04). Poor response to treatment associated significantly with the expression of neuron specific enolase (NSE), β-catenin and PHOX2B in NB patients (P = .021, P = .019 and P = .040; respectively). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of synaptophysin for the diagnosis of BM metastasis in NB patients were (69%, 65.2%, 71.4%, 62.5%; respectively, P = .024). While with β-catenin (93.1%, 43.5%, 67.5%, 83.3%; respectively, P = .003), and PHOX2B expression (65.5%, 34.5%, 59.4%, 50%; respectively, P = .574).
CONCLUSION
β-Catenin could be used as a sensitive and reliable marker for detection of BM metastasis and also a good predictor for resistance to treatment in NB patients. While, PHOX2B gene expression in BM aspirate could be a marker for high risk patients and poor response to treatment.
背景
β-连环蛋白和配对盒基因 2B（PHOX2B）的表达在神经母细胞瘤（NB）患者中被评估为诊断、预后和/或预测标志物。
方法
对 52 例 NB 患者的骨髓（BM）样本进行β-连环蛋白免疫组织化学（IHC）和 PHOX2B 实时 PCR（RT-PCR）检测，并与 12 例健康正常对照（NC）进行比较。将数据与患者的临床病理特征、对治疗的反应和疾病复发相关联。
结果
β-连环蛋白在 40 例（76.92%）患者中表达（P<.001）。而 PHOX2B 在 52 例中的 32 例（61.5%）中表达，其倍数变化为 0.29（0.01-40.0，P=.096）。β-连环蛋白的表达与晚期肿瘤分期、高危、MIBG 和骨扫描阳性结果显著相关（P=.002，P<.001，P=.006，P=.013；分别）。它还与 BM 活检中突触素的表达显著相关（P<.001），具有显著的一致性（K=0.519，P<.001）。β-连环蛋白的表达与 PHOX2B 基因的表达显著相关[32 例中的 28 例（87.5%），P=.04]，且其倍数变化显著（P=.027），具有显著的一致性（K=0.297，P=.022）。PHOX2B 基因表达的倍数变化与患者的高危显著相关（P=.04）。治疗反应不良与神经元特异性烯醇化酶（NSE）、β-连环蛋白和 PHOX2B 在 NB 患者中的表达显著相关（P=.021，P=.019，P=.040；分别）。突触素对 NB 患者 BM 转移的诊断具有（69%，65.2%，71.4%，62.5%；分别，P=.024）的敏感性、特异性、阳性预测值（PPV）和阴性预测值（NPV）。而β-连环蛋白（93.1%，43.5%，67.5%，83.3%；分别，P=.003）和 PHOX2B 表达（65.5%，34.5%，59.4%，50%；分别，P=.574）。
结论
β-连环蛋白可作为检测 BM 转移的敏感、可靠标志物，也是 NB 患者对治疗耐药的良好预测因子。而 PHOX2B 基因在 BM 抽吸物中的表达可能是高危患者和治疗反应不良的标志物。
Zotero 插件