The Discovery and Validation of Biomarkers for the Diagnosis of Esophageal Squamous Dysplasia and Squamous Cell Carcinoma.
The Discovery and Validation of Biomarkers for the Diagnosis of Esophageal Squamous Dysplasia and Squamous Cell Carcinoma.
复制标题
生物标志物的发现和验证可诊断食道鳞状增生和鳞状细胞癌。
DOI:
10.1158/1940-6207.capr-15-0379
复制
发表时间:
2016-07
期刊:
影响因子:
--
通讯作者:
Fitzgerald RC
中科院分区:
文献类型:
--
作者:
Couch G;Redman JE;Wernisch L;Newton R;Malhotra S;Dawsey SM;Lao-Sirieix P;Fitzgerald RC
The 5-year survival rate of esophageal cancer is less than 10% in developing countries, where more than 90% of these cancers are squamous cell carcinomas (ESCC). Endoscopic screening is not feasible on the scale required however non-endoscopic cell-sampling techniques may be feasible. Coupling endoscopic biopsies or non-endoscopic samples with biomarker analysis could reduce the subjectivity associated with both methods and thus improve diagnostic accuracy. The aims of this study were therefore to identify biomarkers for esophageal squamous dysplasia and carcinoma. A publically available dataset was used to identify genes with differential expression in ESCC compared with normal esophagus (NE). Each gene was ranked by a support vector machine separation score. Expression profiles were examined, before validation by qPCR and immunohistochemistry. 800 genes were overexpressed in ESCC compared to NE (p<10−5). Of the top 50 genes, 33 were expressed in ESCC epithelium and not in NE epithelium or stroma using the Protein Atlas website. These were taken to qPCR validation and 20 genes were significantly overexpressed in ESCC compared to NE (p<0.05). TNFAIP3 and CHN1 showed differential expression with immunohistochemistry. TNFAIP3 expression increased gradually through NE, mild, moderate and severe dysplasia, and SCC (p<0.0001). CHN1 staining was rarely present in the top third of NE epithelium and extended progressively towards the surface in mild, moderate, and severe dysplasia, and SCC (p<0.0001). Two novel promising biomarkers for ESCC were identified, TNFAIP3 and CHN1. CHN1 and TNFAIP3 may improve diagnostic accuracy of screening methods for ESCC.