Meng Ze-Wu, Liu Min-Chao, Hong Hai-Jie, Du Qiang, Chen Yan-Ling
1 Department of Hepatobiliary Surgery, The Affiliated Union Hospital of Fujian Medical University, Fuzhou, People's Republic of China.
2 Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, People's Republic of China.
Tumour Biol. 2017 Mar;39(3):1010428317694319. doi: 10.1177/1010428317694319.
The incidence rate of intrahepatic cholangiocarcinoma is rising, and treatment options are limited. Therefore, new biological markers of intrahepatic cholangiocarcinoma are needed. Immunohistochemistry and enzyme-linked immunosorbent assay were applied to analyze the expressions of CD97, CD55, and soluble CD97 in 71 patients with intrahepatic cholangiocarcinoma and 10 patients with hepatolithiasis. CD97 and CD55 were not expressed in hepatolithiatic tissues, but positive expression was observed in 76.1% (54/71) and 70.4% (50/71) of intrahepatic cholangiocarcinoma patients. The univariate analyses indicated that the positive expressions of CD97 and CD55 were related to short intrahepatic cholangiocarcinoma survival of patients (both p = 0.001). Furthermore, CD97 and CD55 expressions and biliary soluble CD97 levels were significantly associated with histological grade (p = 0.004, 0.002, and 0.012, respectively), lymph node metastases (p = 0.020, 0.038, and 0.001, respectively), and venous invasion (p = 0.003, 0.002, and 0.001, respectively). The multivariate analyses indicated that lymph node metastases (hazard ratio: 2.407, p = 0.003), positive CD55 expression (hazard ratio: 4.096, p = 0.003), and biliary soluble CD97 levels (hazard ratio: 2.434, p = 0.002) were independent risk factors for the intrahepatic cholangiocarcinoma survival. The receiver operating characteristic (ROC) curve analysis indicated that when the cutoff values of biliary soluble CD97 were 1.15 U/mL, the diagnostic value for predicting lymph node metastasis had a sensitivity of 87.5% and a specificity of 51.3%. For intrahepatic cholangiocarcinoma patient death within 60 months at a cutoff value of 0.940 U/mL, the diagnostic value sensitivity was 89.3% and the specificity was 93.3%. Biliary soluble CD97 may be a new biological marker for early diagnosis, prediction of lymph node metastasis and poor prognosis, and discovery of a therapeutic target.
肝内胆管癌的发病率正在上升，而治疗选择有限。因此，需要新的肝内胆管癌生物标志物。应用免疫组织化学和酶联免疫吸附测定法分析71例肝内胆管癌患者和10例肝内胆管结石患者中CD97、CD55和可溶性CD97的表达情况。CD97和CD55在肝内胆管结石组织中不表达，但在76.1%（54/71）的肝内胆管癌患者和70.4%（50/71）的肝内胆管癌患者中观察到阳性表达。单因素分析表明，CD97和CD55的阳性表达与肝内胆管癌患者的生存期短相关（两者p均=0.001）。此外，CD97和CD55的表达以及胆汁可溶性CD97水平与组织学分级（分别为p=0.004、0.002和0.012）、淋巴结转移（分别为p=0.020、0.038和0.001）以及静脉侵犯（分别为p=0.003、0.002和0.001）显著相关。多因素分析表明，淋巴结转移（风险比：2.407，p=0.003）、CD55阳性表达（风险比：4.096，p=0.003）和胆汁可溶性CD97水平（风险比：2.434，p=0.002）是肝内胆管癌生存的独立危险因素。受试者工作特征（ROC）曲线分析表明，当胆汁可溶性CD97的截断值为1.15 U/mL时，预测淋巴结转移的诊断价值敏感性为87.5%，特异性为51.3%。对于截断值为0.940 U/mL时60个月内死亡的肝内胆管癌患者，诊断价值敏感性为89.3%，特异性为93.3%。胆汁可溶性CD97可能是早期诊断、预测淋巴结转移和预后不良以及发现治疗靶点的新生物标志物。
