Objective: To analyze and evaluate the expressions and clinical value of tuftelin (TUFT1) and Krüppel-like factor 5 (KLF5) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) tissues. Method: KLF5 mRNA and TUFT1 mRNA transcriptional status in cancer and non-cancer groups were compared according to the Cancer Genome Atlas (TCGA) database. The differences and prognostic value between the groups were analyzed. Postoperative liver cancer and its paired pericancerous tissues, with the approval of the ethics committee, were collected to build tissue chips. The expression of KLF5 and TUFT1 and their intracellular localization were verified by immunohistochemistry. Tissue expression and clinicopathological characteristics were analyzed by immunoblotting. SPSS software was used to analyze the relationship between SPSS and patient prognosis. Results: The transcription level of TUFT1 or KLF5 mRNA was significantly higher in the HCC group than the non-cancer group (P < 0.001), according to TCGA data. Immunohistochemistry and Western blotting examination confirmed the overexpression of TUFT1 and KLF5 in human HCC tissues, which were mainly localized in the cytoplasm and cell membrane. The positivity rates of TUFT1 and KLF5 were 87.1% ( χ(2) = 18.563, P < 0.001) and 95.2% ( χ(2) = 96.435, P < 0.001) in HCC tissues, and both were significantly higher than those in the adjacent group. The expression intensity was higher in stage III-IV than stage I-II of the International Union Against Cancer standard (P < 0.01). The clinicopathological features showed that the abnormalities of the two were significantly related to HBV infection, tumor size, extrahepatic metastasis, TNM stage, and ascites. Univariate analysis was related to tumor size, HBV infection, and survival. Multivariate analysis was an independent prognostic factor for patients with HCC. Conclusion: TUFT1 and KLF5 may both be novel markers possessing clinical value in the diagnosis and prognosis of HBV-related HCC.
目的： 分析乙型肝炎病毒（HBV）相关肝细胞癌（HCC）组织中釉丛蛋白（TUFT1）和锌指蛋白家族Krüppel样因子5（KLF5）表达，评估其对HCC的临床价值。 方法： 依据The Cancer Genome Atlas（TCGA）数据库资料，比较癌及非癌组KLF5 mRNA及TUFT1 mRNA转录状态，分析组间差异及其预后价值；经伦理委员会批准，收集术后肝癌及其配对癌周组织制作组织芯片，以免疫组织化学法验证KLF5和TUFT1表达及其细胞内定位；以免疫印迹法分析组织中表达及其临床病理学特征；以SPSS软件行单/多因素分析其与患者预后的关系。 结果： 依据TCGA资料，HCC组TUFT1或KLF5 mRNA转录水平均显著高于非癌组（P < 0.001）。免疫组织化学检查和蛋白质印迹法证实人HCC组织TUFT1和KLF5过表达，主要定位于细胞质和细胞膜。HCC组织中TUFT1阳性率为87.1%（χ(2) = 18.563，P < 0.001)，KLF5阳性率为95.2%（χ(2) = 96.435，P < 0.001），二者均显著高于癌旁组；在国际抗癌联盟的标准III～IV期其表达强度均高于I～II期（P < 0.01）。临床病理特征显示，二者异常均与患者HBV感染、瘤体大小、伴肝外转移、TNM分期及伴腹水显著相关。单因素分析均与瘤体大小、HBV感染和患者生存率相关；多因素分析均是HCC患者的独立预后因素。 结论： TUFT1和KLF5可能均为HBV相关HCC诊断和预后具有临床价值的新标志物。.
Keywords: Clinicopathological features; Hepatitis B virus; Hepatocellular carcinoma; KLF5; Prognosis; TUFT1.