抗铁蛋白轻链自身抗体是检测肝硬化而非肝癌的血清生物标志物。
Autoantibody Against Ferritin Light Chain is a Serum Biomarker for the Detection of Liver Cirrhosis but Not Liver Cancer.
作者信息
Ren Pengfei, Wang Keyan, Ma Jie, Cao Xiaoqin, Zhao Jiuzhou, Zhao Chengzhi, Guo Yongjun, Ye Hua
机构信息
Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, People's Republic of China.
Henan Key Laboratory of Molecular Pathology, Zhengzhou, People's Republic of China.
出版信息
J Hepatocell Carcinoma. 2022 Mar 29;9:221-232. doi: 10.2147/JHC.S352057. eCollection 2022.
PURPOSE
Ferritin is a protein that plays an important role in iron metabolism, it consists of two subunits: heavy chain (FTH) and light chain (FTL). Elevated expression of FTL is observed in multiple malignancies. Recent studies have found that the frequency of circulating autoantibody against FTL (anti-FTL) increased significantly in hepatocellular carcinoma (HCC). The aim of this study is to verify circulating anti-FTL as a biomarker for the early detection of HCC.
PATIENTS AND METHODS
A total of 1565 participants were enrolled and assigned to two independent validation cohorts, including 393 HCC patients, 379 liver cirrhosis (LC) patients, 400 chronic hepatitis (CH) patients, and 393 healthy subjects. The concentration of serum anti-FTL was measured by indirect Enzyme-Linked Immunosorbent Assay (ELISA). Kruskal-Wallis test was used to compare anti-FTL concentrations between HCC group and three control groups. Percentile 95 of anti-FTL absorbance value of healthy group was selected as the cut-off value to calculate the positive rate in each group. The area under receiver operating characteristic curve (AUC) was used to quantitatively describe its diagnostic value.
RESULTS
The median concentration of anti-FTL in HCC patients was higher than that in CH patients and healthy subjects, but there was no difference between HCC patients and LC patients. Further analysis showed that there was no difference between early stage LC, advanced stage LC, Child-Pugh A HCC, Child-Pugh B HCC and Child-Pugh C HCC. The positive rate of anti-FTL was 12.2% (48/393) in HCC, 13.5% (51/379) in LC, 6.3% (25/400) in CH and 5.1% (20/393) in healthy subjects, respectively. The AUC of anti-FTL to distinguish LC from CH or healthy subjects were 0.654 (95% CI: 0.615-0.692) and 0.642 (95% CI: 0.602-0.681), respectively.
CONCLUSION
Anti-FTL is not a biomarker for the early diagnosis of HCC due to specificity deficiency, but may be helpful for the early detection of LC.
目的
铁蛋白是一种在铁代谢中起重要作用的蛋白质，它由两个亚基组成：重链（FTH）和轻链（FTL）。FTL在多种恶性肿瘤中表达升高。最近的研究发现，肝细胞癌（HCC）患者中循环抗FTL自身抗体（抗FTL）的频率显著增加。本研究的目的是验证循环抗FTL作为HCC早期检测的生物标志物。
患者和方法
共纳入1565名参与者，并将其分配到两个独立的验证队列中，包括393例HCC患者、379例肝硬化（LC）患者、400例慢性肝炎（CH）患者和393名健康受试者。采用间接酶联免疫吸附测定（ELISA）法检测血清抗FTL浓度。采用Kruskal-Wallis检验比较HCC组与三个对照组的抗FTL浓度。选取健康组抗FTL吸光度值的第95百分位数作为截断值，计算各组的阳性率。采用受试者操作特征曲线（AUC）下面积定量描述其诊断价值。
结果
HCC患者抗FTL的中位浓度高于CH患者和健康受试者，但HCC患者与LC患者之间无差异。进一步分析显示，早期LC、晚期LC、Child-Pugh A级HCC、Child-Pugh B级HCC和Child-Pugh C级HCC之间无差异。HCC、LC、CH和健康受试者中抗FTL的阳性率分别为12.2%（48/393）、13.5%（51/379）、6.3%（25/400）和5.1%（20/393）。抗FTL区分LC与CH或健康受试者的AUC分别为0.654（95%CI：0.615-0.692）和0.642（95%CI：0.602-0.681）。
结论
抗FTL因特异性不足，不是HCC早期诊断的生物标志物，但可能有助于LC的早期检测。
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