Serum epithelial membrane protein 1 serves as a feasible biomarker in extrahepatic cholangiocarcinoma.

Abstract

Background: Extrahepatic cholangiocarcinoma is a malignancy that originates from bile duct epithelium with an unfavorable prognosis. Epithelial membrane protein 1 was first discovered in 1995, functioning as an oncogene or anti-tumor gene in various cancers. However, the clinical role of epithelial membrane protein 1 extrahepatic cholangiocarcinoma remained unclear.

Methods: Differentially expressed genes were identified using Gene Ontology and the Kyoto Encyclopedia and Genomes pathway analysis. Out of 183 extrahepatic cholangiocarcinoma patients and 61 healthy controls, the expression level of epithelial membrane protein 1 was detected and compared using reverse transcription-quantitative polymerase chain reaction analysis and western blot assay. Meanwhile, the diagnosis and prognosis of EMP1 in ECCA were measured by receiver operating characteristic and Kaplan-Meier analysis. Finally, the relationship between epithelial membrane protein 1 expression and clinicopathological indexes were compared to further verify the clinical role of epithelial membrane protein 1 in extrahepatic cholangiocarcinoma.

Results: After analyzing data from GSE76297, GSE89749, and GSE26566GO, we found 1554 down-regulated and 1065 up-regulated genes. Through Gene Ontology and Kyoto Encyclopedia and Genomes analysis, extracellular matrix organization, extracellular structure organization, cholesterol metabolism, interleukin-17 signaling pathway, and vitamin digestion and absorption were significantly enriched and involved in targeted differentially expresses genes. Epithelial membrane protein 1 messenger ribonucleic acid was notably decreased in serum samples from extrahepatic cholangiocarcinoma patients, compared with that in healthy controls. Receiver operating characteristic analysis revealed that the area under the curve of epithelial membrane protein 1 messenger ribonucleic acid for the diagnosis of extrahepatic cholangiocarcinoma was 0.9281 (95% CI = 0.8967-0.9595). Moreover, the correlation analysis presented that epithelial membrane protein 1 expression was negatively correlated with lymph node metastasis, tumour node metastasis stage, cancer antigen 19-9 level, and carcinoembryonic antigen level.

Conclusion: Aberrant expression of epithelial membrane protein 1 contributed to distinguishing extrahepatic cholangiocarcinoma patients and healthy controls, and a low expression level of epithelial membrane protein 1 indicated an unfavorable prognosis. Hence, epithelial membrane protein 1 was a feasible and credible biomarker for extrahepatic cholangiocarcinoma diagnosis and prognosis, with high accuracy, sensitivity, and specificity.