Objective: To investigate the expression and clinical significance of human FYVE finger-containing phosphoinositide kinase (PIKFYVE) in hepatocellular carcinoma (HCC) on the basis of cancer genome atlas (The cancer genome atlas, TCGA) database analysis and clinical samples experimental validation. Methods: Based on the data information of 424 clinical samples (including 374 cases of HCC tissues and 50 cases of nontumorous liver tissues) in the TCGA database, Cox regression analysis and Kaplan-Meier method were used to analyse the relationship between the PIKFYVE mRNA expression and the clinical characteristics, prognosis for survival of HCC patients. The relationship between the PIKFYVE gene and immune cell infiltration was examined by correlation analysis between the PIKFYVE gene and 24 immune cells. In addition, we analysed the correlation between the mRNA expression of PIKFYVE gene and RAC-alpha serine/threonine-protein kinase (AKT1), phosphatase and tensin homolog (PTEN), protein kinase C, alpha (PRKCA), inositol polyphosphate-5-phosphatase (INPP5D), phosphoinositide-3-kinase regulatory subunit 1(PIK3R1), Inositol Polyphosphate 4-phosphatase Type II (INPP4B) and phospholipase-C4 gene (PLCB4) in HCC tissues. Meanwhile, paraffin sections of highly differentiated, moderately differentiated, poorly differentiated, and nontumorous liver tissue in the Department of Pathology of the First Affiliated Hospital of Xinjiang Medical University were collected, each of which was 30 cases, and the histopathological observation was carried out by HE staining, and the expression levels of PIKFYVE and Ki67 proteins were verified by immunohistochemistry in each clinical sample. Results: The expression level of PIKFYVE gene in HCC tumours was significantly higher than that in normal liver tissues (P=0.000 2, P<0.01), and the overall survival of patients in the low PIKFYVE expression group was significantly longer than that in the high expression group (HR=1.57, 95%CI: 1.10～2.25, P=0.014). The results of Univariate Cox regression analysis showed that there was an effect of TNM stage, pathological stage, tumour status and residual tumour on Overall survival (OS) (P<0.05), and the expression level of PIKFYVE had an effect on OS survival (P<0.05); the PIKFYVE prognostic risk model score ratio was HR=1.533 (1.077-2.181, P=0.018). Multivariate Cox regression analysis showed a PIKFYVE prognostic risk model score ratio HR=1.481 (0.886-2.476, P=0.134) and an area under the Receiver Operating Characteristic curve of 0.640, which was greater than 0.5, suggesting that the PIKFYVE prognostic risk model has a predictive value in survival prediction. Correlation analysis showed that the expression level of PIKFYVE was highly correlated with immune cell infiltration and TP53 (P<0.01). The immunohistochemistry staining results showed that the expression of PIKFYVE in HCC tissues was significantly higher than that of nontumorous tissues (P<0.05), and there was a negative correlation with the degree of differentiation. Conclusion: PIKFYVE, as an independent risk factor for HCC, is expected to be developed as a clinical diagnostic biomarker for HCC, which will provide a reference for new drugs for the treatment of HCC.
目的： 基于癌症基因组图谱（TCGA）数据库和临床样本的实验验证分析肝细胞癌（HCC）中含FYVE指磷酸肌醇激酶（PIKFYVE）基因mRNA的表达情况及其临床意义。 方法： 基于TCGA数据库中的424例临床样本数据资料（包括HCC组织374例，非肿瘤肝组织50例），采用Kaplan-Meier法和Cox回归分析评估PIKFYVE基因表达与HCC患者生存预后及其临床特征的关系。通过PIKFYVE基因与24种免疫细胞的相关性分析，考察PIKFYVE基因与免疫细胞浸润的关系。此外，通过分析HCC组织中PIKFYVE基因的表达与RAC-α-丝氨酸/苏氨酸蛋白激酶（AKT1）、磷脂酰肌醇-3-激酶抑制蛋白（PTEN）、蛋白激酶C，α（PRKCA）、肌醇多聚磷酸5磷酸酶（INPP5D）、磷酸肌醇3激酶调控亚基1（PIK3R1）、肌醇多聚磷酸-4-磷酸酶Ⅱ型（INPP4B）和磷酸肌醇特异性磷脂酶- C4基因（PLCB4）的mRNA表达水平的相关性。同时收集新疆医科大学第一附属医院病理科HCC患者的高分化、中分化、低分化以及非肿瘤肝组织石蜡切片，各30份，通过HE染色法进行组织病理学观察；且用免疫组织化学法对各临床样本中PIKFYVE、Ki67蛋白表达水平进行验证。计量资料组间数据比较采用t检验，计数资料组间比较采用χ2检验、Wilcoxon秩和检验，生存分析采用Kaplan-Meier法。 结果： PIKFYVE基因在HCC肿瘤中的表达水平高于正常肝组织（P<0.01），PIKFYVE低表达组患者的总生存期明显长于高表达组（HR=1.57，95%CI：1.10～2.25，P=0.014）。单因素Cox回归分析结果显示肿瘤分期、病理分期、肿瘤状况和残余肿瘤对OS生存期存在影响（P<0.05），PIKFYVE的表达水平对OS生存期存在影响（P<0.05）；PIKFYVE预后风险模型评分比HR=1.533（1.077-2.181，P=0.018）。多因素Cox风险比例回归分析显示PIKFYVE预后风险模型评分比HR=1.481（0.886～2.476，P=0.134），且受试者操作特征曲线下面积为0.640，表明PIKFYVE预后风险模型在生存预测中具有预测价值。相关性分析结果显示PIKFYVE的表达水平与免疫细胞浸润以及TP53高度相关（P<0.01）。免疫组织化学染色结果显示，HCC组织样本中的PIKFYVE表达水平显著高于非肿瘤肝组织（P<0.05），且与分化程度呈负相关关系。 结论： PIKFYVE作为HCC的独立危险因子，有望开发成HCC临床诊断的生物标志物，为治疗HCC的新药提供参考依据。.