Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, China.
Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, China.
EBioMedicine. 2019 Feb;40:422-431. doi: 10.1016/j.ebiom.2018.12.063. Epub 2019 Jan 9.
We aimed to screen a specific secretory protein that could serve as blood diagnostic marker for cholangiocarcinoma (CCA).
Starting with the analysis of gene expression profiles in tumor tissues and matched normal tissues from cases with CCA and hepatocellular carcinoma (HCC), we identified peptidase inhibitor 15 (PI15) was a potential diagnostic marker for CCA. We demonstrated PI15 expression levels in CCA, HCC, and normal liver tissues. Furthermore, quantitative enzyme-linked immunosorbent assay (ELISA) assessed plasma PI15 levels in CCA (n = 61), HCC (n = 72), benign liver disease (n = 28), chronic hepatitis B (CHB) patients (n = 45), and healthy individuals (n = 45). The diagnostic value of PI15 was estimated by the area under the receiver operating characteristic (ROC) curve (AUC).
The positive rate of PI15 expression was 70% in CCA and only 9.1% in HCC; PI15 was not detected in normal liver tissue. High levels of plasma PI15 were evident in CCA patients, whereas only low levels were observed in cases involving HCC, benign liver disease, CHB patients, and healthy individuals. Plasma PI15 levels in CCA patients were obviously reduced (p = .0014) after surgery. The AUC of plasma PI15 for discriminating between CCA and HCC was 0.735. Furthermore, with a specificity of 94.44%, the combination of CA19-9 (>98.5 U/ml) and PI15 (>13 ng/ml) yielded a sensitivity of 80.39% for CCA and HCC.
PI15 exhibits promise as a novel marker for predicting the diagnosis and follow-up of CCA patients. FUND: Natural Science Research Foundation of Anhui Province and Natural Science Foundation of China.
我们旨在筛选一种可作为胆管癌（CCA）血液诊断标志物的特异性分泌蛋白。
从 CCA 和肝细胞癌（HCC）病例的肿瘤组织和匹配的正常组织的基因表达谱分析开始，我们确定肽酶抑制剂 15（PI15）是 CCA 的潜在诊断标志物。我们展示了 CCA、HCC 和正常肝组织中的 PI15 表达水平。此外，定量酶联免疫吸附试验（ELISA）评估了 CCA（n=61）、HCC（n=72）、良性肝病（n=28）、慢性乙型肝炎（CHB）患者（n=45）和健康个体（n=45）的血浆 PI15 水平。通过接收者操作特征（ROC）曲线下面积（AUC）评估 PI15 的诊断价值。
PI15 在 CCA 中的阳性率为 70%，而在 HCC 中仅为 9.1%；PI15 未在正常肝组织中检测到。CCA 患者的血浆 PI15 水平较高，而 HCC、良性肝病、CHB 患者和健康个体的水平较低。CCA 患者手术后血浆 PI15 水平明显降低（p=0.0014）。血浆 PI15 区分 CCA 和 HCC 的 AUC 为 0.735。此外，CA19-9（>98.5 U/ml）和 PI15（>13 ng/ml）的组合对 CCA 和 HCC 的灵敏度为 80.39%，特异性为 94.44%。
PI15 有望成为预测 CCA 患者诊断和随访的新型标志物。
安徽省自然科学基金和国家自然科学基金。
