摘要目的: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的磷酸肌醇3-磷酸5-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（ PLCB4）基因的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，通过苏木精-伊红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总体生存期存在影响（ P<0.05）， PIKFYVE的表达水平对总体生存期存在影响（ P<0.05）；PIKFYVE预后风险模型评分比 HR=1.533（95% CI：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（95% CI：0.886～2.476， P=0.134），且受试者操作特征曲线下面积为0.559，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<0.01），且与分化程度呈负相关。 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，为研发治疗HCC的新药提供参考依据。

abstractsObjective:To experimentally validate clinical samples, analyze the mRNA expression of the FYVE domain containing phosphatidylinositol 3-phosphate 5 kinase ( PIKFYVE) gene, and its clinical significance based on the Cancer Genome Atlas (TCGA) database in hepatocellular carcinoma (HCC). Methods:Data information on 424 clinical samples (including 374 cases of HCC tissues and 50 cases of non-tumorous liver tissues) were collected based on the TCGA database. Cox regression analysis and the Kaplan-Meier method were used to analyze the relationship between mRNA expression of the PIKFYVE gene and the clinical characteristics as well as survival prognosis in patients with HCC. The relationship between the PIKFYVE gene and immune cell infiltration was examined by correlation analysis with 24 kinds of immune cells. In addition, the mRNA expression level of the 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 C beta 4 ( PLCB4) gene correlations were analyzed in HCC tissues. At the same time, paraffin sections of highly differentiated, moderately differentiated, poorly differentiated, and non-tumor liver tissues from patients with HCC were collected from the Department of Pathology of the First Affiliated Hospital of Xinjiang Medical University. The histopathological observation was performed by HE staining. Immunohistochemistry was used to verify the expression levels of the PIKFYVE and Ki67 proteins in each clinical sample. The t-test was used for intergroup comparison of continuous data. The χ2 test and Wilcoxon rank sum test were used for intergroup comparison of enumeration data. The Kaplan-Meier method was used for survival analysis. Results:The expression level of the PIKFYVE gene was higher in the HCC tumor than that in normal liver tissue ( P<0.01). The overall survival time of patients was significantly longer in the low expression group 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 tumor stage, pathological grade, tumor status, residual tumor, and PIKFYVE expression level all had an effect on OS ( P<0.05). The PIKFYVE prognostic risk model had a proportionate score of HR=1.533 (95% CI: 1.077～2.181, P=0.018). Multivariate Cox risk regression analysis showed that the PIKFYVE prognostic risk model had a proportionate score of HR=1.481 (95% CI: 0.886～2.476, P=0.134) and an area under the receiver operating characteristic curve of 0.559, indicating that it had predictive value for survival prediction. The results of the correlation analysis showed that the expression level of PIKFYVE was strongly correlated with immune cell infiltration and TP53 ( P<0.01). The results of immunohistochemical staining showed that the expression level of PIKFYVE was significantly higher in HCC tissue samples than that in non-tumor liver tissues ( P<0.01), and was negatively correlated with the degree of differentiation. Conclusion:PIKFYVE, as an independent risk factor, is expected to be developed into a biomarker for clinical diagnosis, offering a reference for novel therapeutic agents in HCC.