Cancer Biomarker Group, Institute of Life Sciences, Swansea University, Swansea, SA2 8PP, United Kingdom.
Department of Gastroenterology, Singleton Hospital, Swansea, SA2 8QA, United Kingdom.
Sci Rep. 2019 Mar 26;9(1):5168. doi: 10.1038/s41598-019-41490-w.
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.
磷脂酰肌醇聚糖 A （PIG-A）基因突变分析表型可检测红细胞突变，本研究评估了胃食管反流病（GORD）-巴雷特化生（BM）-食管腺癌（OAC）模型中红细胞突变与肿瘤进展的相关性。对内镜患者进行静脉穿刺，并用荧光标记糖基磷脂酰肌醇（GPI）锚定蛋白；CD55 和 CD59。通过流式细胞术，对 GPI 锚定阴性红细胞（突变体）进行评分，并比较各组间的差异。本研究共纳入 200 例 OAC 患者和 137 例健康志愿者。与 GORD 患者（p<0.001）和健康志愿者（p<0.001）相比，OAC 患者的红细胞突变频率（EMF）增加了三倍。在 OAC 患者中，较高的 EMF 与肿瘤分期恶化（p=0.014）、淋巴结受累（p=0.019）和转移疾病（p=0.008）相关。化疗患者的 EMF 比 GORD 患者高 19 倍以上。患者进一步分为非肿瘤性疾病组和高级别异型增生/癌症组，高 EMF 可正确分类 72.1%的病例。在非肿瘤性疾病组中，阿司匹林使用者的 EMF 较低（p=0.001），BMI（p=0.03）和年龄（p<0.001）与 EMF 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，该检测方法有助于检测 OAC，可能是疾病进展的有用预测指标。
