Affiliation:
1. Department of Gastroenterology The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases Shijiazhuang Hebei Province China
2. Department of Gastroenterology Hengshui People's Hospital Hengshui Hebei Province China
3. Department of Rheumatology and immunology The Second Hospital of Hebei Medical University Shijiazhuang Hebei Province China
Abstract
AbstractCholangiocarcinoma often remains undetected until advanced stages due to the lack of reliable diagnostic markers. Our goal was to identify a unique secretory protein for cholangiocarcinoma diagnosis and differentiation from other malignancies, benign hepatobiliary diseases, and chronic liver conditions. We conducted bulk RNA‐seq analysis to identify genes specifically upregulated in cholangiocarcinoma but not in most other cancers, benign hepatobiliary diseases, and chronic liver diseases focusing on exocrine protein‐encoding genes. Single‐cell RNA sequencing examined subcellular distribution. Immunohistochemistry and enzyme‐linked immunosorbent assays assessed tissue and serum expression. Diagnostic performance was evaluated via receiver‐operating characteristic (ROC) analysis. Inter‐alpha‐trypsin inhibitor heavy chain family member five (ITIH5), a gene encoding an extracellular protein, is notably upregulated in cholangiocarcinoma. This elevation is not observed in most other cancer types, benign hepatobiliary diseases, or chronic liver disorders. It is specifically expressed by malignant cholangiocytes. ITIH5 expression in cholangiocarcinoma tissues exceeded that in nontumorous bile duct, hepatocellular carcinoma, and nontumorous hepatic tissues. Serum ITIH5 levels were elevated in cholangiocarcinoma compared with controls (hepatocellular carcinoma, benign diseases, chronic hepatitis B, and healthy individuals). ITIH5 yielded areas under the ROC curve (AUCs) from 0.839 to 0.851 distinguishing cholangiocarcinoma from controls. Combining ITIH5 with carbohydrate antigen 19‐9 (CA19‐9) enhanced CA19‐9's diagnostic effectiveness. In conclusion, serum ITIH5 may serve as a novel noninvasive cholangiocarcinoma diagnostic marker.
Funder
Natural Science Foundation of Hebei Province
Cited by
1 articles.
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