Feng Hao, Fang Fang, Yuan Lei, Xiao Mingjia, Yang Xiao-Yu, Huang Yao
Department of Gynecology and Obstetrics, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200090, P.R. China.
Department of Radiotherapy, Navy Medical University, Shanghai 200433, P.R. China.
Exp Ther Med. 2019 May;17(5):4073-4079. doi: 10.3892/etm.2019.7455. Epub 2019 Mar 29.
Complement factor H-related protein 1 (CFHL1) was recently reported to be a potential biomarker in several types of cancer. CFHL1, however, has not been found to be of prognostic value in hepatocellular carcinoma (HCC) to date. In the present study, the expression levels of CFHL1 were evaluated in 8 pairs fresh frozen tissue samples using western blotting. Furthermore, the expression level of CFHL1 was evaluated in 76 pairs of formalin-fixed, paraffin-embedded (FFPE) HCC and peritumoral tissues (expression pattern cohort), and 278 FFPE HCC tissues (prognostic cohort) using tissue microarray-based immunohistochemistry. The Kaplan-Meier method, Cox regression proportional hazard model and receiver operating characteristic curve analysis were used to evaluate prognostic factors. The expression level of CFHL1 was reduced in HCC tissues in 67.1% (51/76) of the cases compared with the corresponding peritumoral tissues. Survival analyses indicated that patients with HCC with low CFHL1 expression had a worse time-to-recurrence (TTR) and overall survival (OS) compared with those with high CFHL1 expression in the prognostic cohort (P=0.002 for OS and P=0.017 for TTR). Both univariate and multivariate analyses indicated that CHFL1 was an independent prognostic factor for TTR and OS (P=0.017 and P=0.002, respectively). In addition, The Cancer Genome Atlas (TCGA) and Human Protein Atlas were used for further validation. Furthermore, a prognostic model included tumor size, tumor number, liver cirrhosis and CFHL1 expression was evaluated. The results of the present study demonstrated that CFHL1 was downregulated in HCC and its level was associated with patient prognosis; therefore, CFHL1 is a potential prognostic marker for HCC.
补体因子H相关蛋白1（CFHL1）最近被报道为几种癌症的潜在生物标志物。然而，迄今为止尚未发现CFHL1在肝细胞癌（HCC）中具有预后价值。在本研究中，使用蛋白质印迹法评估了8对新鲜冷冻组织样本中CFHL1的表达水平。此外，使用基于组织芯片的免疫组织化学方法，在76对福尔马林固定、石蜡包埋（FFPE）的HCC组织和癌旁组织（表达模式队列）以及278例FFPE HCC组织（预后队列）中评估了CFHL1的表达水平。采用Kaplan-Meier法、Cox回归比例风险模型和受试者工作特征曲线分析来评估预后因素。与相应的癌旁组织相比，67.1%（51/76）的HCC组织中CFHL1的表达水平降低。生存分析表明，在预后队列中，CFHL1低表达的HCC患者与CFHL1高表达的患者相比，复发时间（TTR）和总生存期（OS）更差（OS的P=0.002，TTR的P=0.017）。单因素和多因素分析均表明，CHFL1是TTR和OS的独立预后因素（分别为P=0.017和P=0.002）。此外，使用癌症基因组图谱（TCGA）和人类蛋白质图谱进行进一步验证。此外，还评估了一个包括肿瘤大小、肿瘤数量、肝硬化和CFHL1表达的预后模型。本研究结果表明，CFHL1在HCC中表达下调，其水平与患者预后相关；因此，CFHL1是HCC的潜在预后标志物。
