Developing a blood-based gene mutation assay as a novel biomarker for oesophageal adenocarcinoma
Developing a blood-based gene mutation assay as a novel biomarker for oesophageal adenocarcinoma
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DOI：
10.1038/s41598-019-41490-w
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发表时间：
2019-03-26
影响因子：
4.6
通讯作者：
Jenkins, Gareth J.
中科院分区：
文献类型：
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作者：
Haboubi, Hasan N.;Lawrence, Rachel L.;Jenkins, Gareth J.
磷脂酰肌醇葡聚糖A类(PIG-A)基因突变分析表型测定红细胞突变，在此评估其与胃食道反流病(GORD)-巴雷特化生(BM)-食管腺癌(OAC)模型中肿瘤进展的相关性。内窥镜患者接受静脉穿刺术，红细胞进行糖基磷脂酰肌醇(GPI)锚定蛋白CD55和CD59的荧光染色。用流式细胞仪对GPI锚定阴性红细胞(突变型)进行评分，并进行组间比较。这项研究招募了200名患者和137名健康志愿者。OAC患者的红细胞突变频率是GORD患者(P<；0.001)和健康志愿者(P<；0.001)的三倍。在OAC患者中，高电动势与肿瘤分期恶化(p=0.014)、淋巴结转移(p=0.019)和转移性疾病(p=0.008)相关。化疗患者的EMF是GORD患者的19倍以上。进一步将患者分为非肿瘤性疾病组和高度不典型增生/癌组，高电动势正确分型的比例为72.1%。在非肿瘤组中，服用阿司匹林的患者电动势较低(p=0.001)，体重指数(p=0.03)与年龄(p<；0.001)和电动势呈正相关。吸烟者的EMF是不吸烟者的两倍多(p=0.011)。结果表明，这项测试可以帮助检测OAC，并可能是一个有用的疾病进展预测。
The Phosphatidylinositol glycan class A (PIG-A) gene mutation assay phenotypically measures erythrocyte mutations, assessed here for their correlation to neoplastic progression in the gastro-oesophageal reflux disease (GORD)-Barrett's metaplasia (BM)-oesophageal adenocarcinoma (OAC) model. Endoscopy patients underwent venipuncture and erythrocytes fluorescently stained for glycosyl phosphatidylinositol (GPI)-anchored proteins; CD55 and CD59. Using flow cytometry, GPI-anchor negative erythrocytes (mutants) were scored and compared amongst groups. The study enlisted 200 patients and 137 healthy volunteers. OAC patients had a three-fold increase in erythrocyte mutant frequency (EMF) compared to GORD patients (p < 0.001) and healthy volunteers (p < 0.001). In OAC patients, higher EMF was associated with worsening tumour staging (p = 0.014), nodal involvement (p = 0.019) and metastatic disease (p = 0.008). Chemotherapy patients demonstrated EMF's over 19-times higher than GORD patients. Patients were further classified into groups containing those with non-neoplastic disease and those with high-grade dysplasia/cancer with 72.1% of cases correctly classified by high EMF. Within the non-neoplastic group, aspirin users had lower EMF (p = 0.001) and there was a positive correlation between body mass index (p = 0.03) and age (p < 0.001) and EMF. Smokers had EMF's over double that of non-smokers (p = 0.011). Results suggest this test could help detect OAC and may be a useful predictor of disease progression.