PRR11在肝癌中的表达及其与预后的关系

摘 要：［目的］ 研究肝癌组织中富含脯氨酸蛋白11(PRR11)表达与肝癌临床病理参数之间的关系,以及PRR11表达对肝癌患者预后的影响。［方法］ 通过构建含243例肝癌的组织芯片,用免疫组化方法检测PRR11蛋白在肝癌组织中的表达。［结果］ 243例肝癌组织标本中,PRR11高表达与性别、AFP水平、HBSAg、HBeAg水平有关。Kaplan-Meier 生存分析显示：PRR11高表达患者总生存期短于低表达患者(36.5个月vs 46.3个月,P=0.007) ,且病理分期(Ⅰ～Ⅱ vs Ⅲ～Ⅳ：60.7个月vs 19.5个月,P=0.001)、主瘤直径(≤5cm vs ＞5cm：55.9个月vs 19.5个月,P<0.001)、有无癌栓(无 vs 有：49.3个月 vs 22.7个月,P<0.001)、子灶数目(≤1个 vs ＞1个：50.0个月vs 22.5个月,P<0.001)与总生存期均显著相关。Cox风险回归模型分析显示PRR11表达是肝癌患者的独立预后因素（P=0.007)。［结论］ PRR11在部分肝癌组织中高表达,是肝癌患者独立的不良预后因素。     

miR －375在食管癌中的研究进展

MicroRNAs（miRNAs）是一类非蛋白编码的微小 RNA 分子,在人类多种生理和病理过程中起着重要的调节作用。大量研究表明,miRNAs 异常表达是肿瘤的重要特征之一。其中,miR －375和食管癌关系十分密切。miR －375在食管癌组织和血清中的低表达,表明患者预后较差。     

miR－320a表达与结直肠癌患者预后的关系

目的：探讨miR－320a与结直肠癌患者的临床病理特征及预后的相关性。方法选取2010年1月至2013年3月在本科室收治的65例已经配对的癌旁正常组织和结直肠癌组织,采用实时定量PCR的方法检测癌旁正常组织和癌组织中miR－320a的表达情况,分析miR－320a表达情况与结直肠癌患者的临床病理特点及生存预后的关系。结果结直肠癌组织中miR－320a表达量明显低于癌旁正常组织（P＜0．001）。结直肠癌患者组织中miR－320a的表达与肿瘤分化程度、TNM分期和CEA水平有关（均P＜0．05）,而与年龄、性别、肿瘤部位无关（均P＞0．05）。生存分析结果显示miR－320a高表达的结直肠癌患者术后总体预后明显优于miR－320a低表达者,两组患者的5年生存率分别为54．7％和31．4％（P＝0．022）。结论 miR－320a 可能作为结直肠癌患者预后的预测指标。miR－320a过表达可能提示结直肠癌患者肿瘤生物学行为较佳。     

WFDC-1基因在原发性肝癌组织中的表达及其临床意义

目的检测WFDC-1基因在肝癌和正常肝组织的表达差异并探讨其临床意义。方法采用荧光实时定量PCR（FQ-RT-PCR）法检测30例肝癌组织及相应远端正常肝组织WFDC-1mRNA的表达,分析其表达与肝癌患者临床特征的相关性。结果 WFDC-1mRNA在肝癌组织中的表达水平（0.050±0.026）明显低于远端正常肝组织（0.113±0.040）,两者差别有统计学意义（P〈0.05）。WFDC-1mRNA在肝癌中的表达水平与HBsAg水平有关,合并HBsAg阳性的肝细胞癌（HCC）中的表达低于HBsAg阴性HCC组（P〈0.05）,而与年龄、性别、肿瘤大小、临床分期、AFP及有无肝硬化无关（P〉0.05）。结论肝癌组织中WFDC-1基因表达水平明显低于相应正常肝组织,提示WFDC-1表达与降低肿瘤发生有一定的相关性,为潜在的抑癌基因。     

WFDC-1基因在原发性肝癌组织中的表达及其临床意义

目的检测WFDC-1基因在肝癌和正常肝组织的表达差异并探讨其临床意义。方法采用荧光实时定量PCR(FQ-RT-PCR)法检测30例肝癌组织及相应远端正常肝组织WFDC-1mRNA的表达,分析其表达与肝癌患者临床特征的相关性。结果 WFDC-1mRNA在肝癌组织中的表达水平(0.050±0.026)明显低于远端正常肝组织(0.113±0.040),两者差别有统计学意义(P<0.05)。WFDC-1mRNA在肝癌中的表达水平与HBsAg水平有关,合并HBsAg阳性的肝细胞癌(HCC)中的表达低于HBsAg阴性HCC组(P<0.05),而与年龄、性别、肿瘤大小、临床分期、AFP及有无肝硬化无关(P>0.05)。结论肝癌组织中WFDC-1基因表达水平明显低于相应正常肝组织,提示WFDC-1表达与降低肿瘤发生有一定的相关性,为潜在的抑癌基因。     

酪氨酸蛋白激酶在肝癌组织中的表达及其与肝癌患者预后的关系

目的:检测肝癌组织、癌旁组织中酪氨酸蛋白激酶ERK、C-Jun和JAK2的表达,并探讨其临床病理意义.方法:收集武警后勤学院附属医院肝癌手术切除标本60例,采用免疫组化SP法检测ERK、C-Jun和JAK2在肝癌组织、癌旁组织中的表达;采用比例风险模型Cox进行多因素分析,探讨影响肝癌患者预后的因素.结果:肝癌组织中ERK、C-Jun和JAK2平均D值为(0.23 ±0.03)、(0.18 ±0.06)、(0.19 ±0.07),明显高于癌旁组织的[(0.16±0.02),(0.13 ±0.02),(0.14 ±0.05,P＜0.01];Cox单因素分析显示,C-Jun和JAK2与肝癌患者预后密切相关(P ＜0.05);Cox多因素分析显示,JAK2是影响肝癌患者预后的重要独立因素.结论:JAK2是影响肝癌患者预后的重要因素,可能作为判断肝癌患者预后的独立指标.     

AGGF1在肝癌中的表达及与预后的关系

目的:探索AGGF1在肝癌中的表达情况及与肝癌患者预后的关系。方法:对180例肝癌组织及癌旁组织进行AGGF1免疫组织化学检测,并对其表达与患者预后的关系进行分析。结果:AGGF1在肝癌组织中的表达比癌旁组织高(P<0.001),Kaplan-Meier曲线分析发现AGGF1表达高的患者生存较差(P=0.002)。COX回归模型分析发现AGGF1可以作为一个独立指标预测肝癌患者术后生存。结论:肝癌患者AGGF1高表达预示着较差预后,并且AGGF1可以作为一个独立因素来预测肝癌患者术后生存。     

SPARCL1在肝癌中的表达及其临床意义

目的 探讨SPARCL1表达与肝癌患者术后预后的关系.方法 收集154例肝癌患者的术后石蜡切片标本、临床病理资料及随访资料,采用免疫组化染色方法对石蜡切片组织中SPARCL1进行检测.结果 不同肝癌组织中SPARCL1的水平具有差异;SPARCL1表达下调与门脉癌栓、病理分化差、TNM分期晚和BCLC分期晚等恶性指标显著相关;SPARCL1表达下调的肝癌患者其中位生存时间显著缩短(40.6个月 vs118.7个月,P=0.002).结论 SPARCL1在肝癌中表达下调,提示肝癌患者的预后不良.     

WFDC1基因在肝癌中的表达及其诊断和预后价值

目的：研究WFDC1基因在肝癌组织和细胞中的表达变化,探讨其与肝癌临床病理指标及生存预后之间的关系,为肝癌的诊断以及预后判断提供参考依据。方法：采用qPCR法分别检测肝癌患者的肿瘤组织和癌旁组织、MC-LR诱导的人肝细胞L02恶性转化细胞和肝癌细胞株SMMC-7721、HepG2、Hep3B、Huh-7中WFDC1 mRNA的表达水平。基于TCGA数据库,分析WFDC1基因在肝癌患者肿瘤组织（331例）和癌旁组织（50例）中的表达及其与临床病理指标和生存预后的关系。结果：qPCR检测结果表明,与癌旁组织比较,WFDC1 mRNA在肝癌组织、MC-LR诱导的L02恶性转化细胞以及肝癌细胞中的表达均显著下调（P < 0.05）。TCGA数据库中WFDC1 mRNA表达分析也表明,肝癌组织的表达显著低于癌旁组织（P < 0.01）,且WFDC1 mRNA的表达下调与肿瘤分级和临床分期高度相关（P < 0.05）。Kaplan-Meier分析表明,WFDC1 mRNA高表达患者生存时间高于低表达患者（Log-rank=4.80,P < 0.05）。ROC曲线分析结果表明,WFDC1 mRNA是一个特异度和灵敏度较好的肝癌诊断指标（AUC=0.829）。结论：WFDC1基因可能是一个抑癌基因,检测该基因的表达水平对肝癌患者的诊断和预后判断具有参考价值。     

LYRIC在人肝癌组织中的表达及其临床意义

目的： 检测LYRIC分子在肝癌和癌旁组织中的表达,探讨LYRIC分子与肝癌患者临床病理特征的关系及其对预后判断的指导意义。 方法： 收集2005年1月至2013年12月沈阳军区总医院和中国医科大学附属盛京医院的87例肝癌患者肝癌及其癌旁组织切除标本,采用Real-time PCR和免疫组织化学染色等方法从基因和蛋白水平检测肝癌患者的癌组织及相应的癌旁组织中LYRIC分子的表达,结合患者病理指标、病理分型和预后随访资料分析LYRIC分子表达的临床意义。 结果： 在基因水平检测发现, LYRIC 基因在56例肝癌组织中表达高于癌旁组织,高表达率为64.7%（56/87）;在蛋白水平检测发现,LYRIC蛋白在87例肝癌组织中均表达,且在肝癌组织中的表达显著高于癌旁组织（2.16±0.87 vs 1.63±0.88, P =0 000 1）。在肝癌组织中LYRIC分子的高、低表达可较好地预测肝癌患者的预后情况,LYRIC分子高表达患者预后较差（Log-rank10.236, P =0.001）;多因素分析提示,LYRIC高表达（HR=2.19）、转移（HR=2.44）及肿瘤分期（HR=2.01）是影响肝癌总体生存期的独立危险因素,而与肿瘤直径及是否有病毒感染无关。 结论： LYRIC分子在肝癌组织中高表达,且其表达水平与肝癌的临床分期、转移能力和临床预后密切相关,是肝癌潜在的预后判断指标。     

miR -542-5p 在浆液性卵巢癌中的表达及意义

目的：检测 miR -542-5p 在浆液性卵巢癌中的表达,并分析 miR -542-5p 的表达与浆液性卵巢癌临床病理特征之间的关系,探讨其意义。方法：采用实时荧光定量 PCR 技术分析100例浆液性卵巢癌组织及50例正常输卵管伞端组织中 miR -542-5p 的表达。结果：浆液性卵巢癌组织中 miR -542-5p 的表达显著低于正常输卵管伞端组织（P ﹤0.05）。miR -542-5p 的表达与浆液性卵巢癌各临床病理特征之间差异均无统计学意义（P ﹥0.05）。结论：miR -542-5p 可能作为抑癌基因参与了浆液性卵巢癌的发生,对于卵巢癌的早期诊断及治疗具有潜在意义。     

宫颈癌组织miR-221的表达及其与HPV感染的关联

目的探讨miR-221在宫颈癌组织中的表达情况及其与HPV感染的关系。方法经HC2法检测宫颈癌患者高危型HPV病毒,分别收集30例高危型HPV（HR-HPV）阳性及5例阴性的宫颈癌标本。同时选取30例同期因良性疾病住院患者的正常宫颈组织为对照,通过RT-PCR方法检测宫颈组织中miR-221的表达情况,初步探讨miR-221与宫颈癌的发生发展及HPV感染的关系。并通过转染的方法分别将miR-221和anti-miR-221转入HPVl6阴性的宫颈癌细胞株C33a中和HPVl6阳性的宫颈癌细胞株Caski,观察其对C33a和Caski转移和侵袭的影响。结果miR-221在宫颈癌组织中的阳性表达率显著高于正常宫颈组织（P〈0．01）,miR-221的表达水平与患者有无淋巴结转移、临床病理分级、临床分期密切相关（P〈0．01）;miR-221在HR—HPV阳性癌组织中的阳性表达率显著高于HR-HPV阴性癌组织（P〈0．01）;转染miR-221可促进Caski和C33a细胞转移和侵袭,而转入anti-miR-221可降低Caski和C33a细胞转移和侵袭能力,转染后两组细胞增殖率和凋亡率变化情况比较差异具有统计学意义（P〈0．05）。结论宫颈癌组织中miR-221表达升高与宫颈癌的发生发展及HPV感染密切相关。     

The expression and prognostic value of GLYATL1 and its potential role in hepatocellular carcinoma

BackgroundGlycine-N-acyltransferase-like 1 (GLYATL1), which is involved in the detoxification of endogenous and exogenous acyl-CoA, promotes glutamine metabolism in xenobiotic metabolism. Recent evidence suggests an association between GLYATL1 and tumors. However, there are few comprehensive analyses of GLYATL1 in cancers. We evaluated the expression and prognostic value of GLYATL1 and explored the mechanism underlying the association between GLYATL1 and cancers.MethodsGLYATL1 mRNA expression across cancers was investigated in the Oncomine database and confirmed in the UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) databases. Next, its prognostic value in different cancers was revealed by PrognoScan and Kaplan-Meier plotter. According to clinicopathologic features, we conducted a subgroup analysis of the prognosis of GLYATL1 in a cohort of hepatocellular carcinoma (HCC) patients from The Cancer Genome Atlas (TCGA) and the {"type":"entrez-geo","attrs":{"text":"GSE116174","term_id":"116174"}}GSE116174 dataset. We further investigated the GLYATL1 promoter methylation profile in HCC. Next, a protein-protein interaction (PPI) network was constructed via the Search Tool for the Retrieval of Interacting Genes (STRING) database. Finally, we utilized gene set enrichment analysis (GSEA) to identify significantly enriched pathways and confirmed their associations using the Tumor Immune Estimation Resource (TIMER) and GEPIA databases.ResultsGLYATL1 is downregulated in many cancers and indicates a poor prognosis. Specifically, low GLYATL1 expression was associated with short overall survival (OS) in HCC patients. Interestingly, GLYATL1 expression was associated with poor OS in stage I-II HCC patients and was revealed as an independent prognostic factor. The promoter methylation level of GLYATL1 in HCC tissue was significantly higher than that in normal liver tissue. The PPI network suggested that GLYATL1 is co-expressed with ten genes, including CNGA3 and GNB5. GSEA revealed that GLYATL1 is predominantly negatively enriched in xenobiotic metabolism, and the gene association analysis in TIMER and GEPIA showed a significantly negative association between the expression of GLYATL1 and the expression of most genes involved in mitochondrial glutamine metabolism, including SLC1A5 and SLC1A11.ConclusionsOur study is the first to shed light on the expression and prognostic value of GLYATL1 in cancers and provide a potential regulatory mechanism underlying HCC development.     

miR-212在上皮性卵巢癌中表达的临床意义

目的:本研究探讨上皮性卵巢癌中miR-212的表达及其与临床病理特征的关系。方法:采用茎环实时荧光逆转录聚合酶链反应Real-time RT-PCR检测我院46例上皮性卵巢癌组织及癌旁良性组织中miR-212表达,并对临床病理数据进行分析。Transwell 检测转染miR-212 mimic对SKOV3细胞运动、侵袭的影响,Western Blot检测E-cadherin和Vimentin蛋白表达。结果: 46例上皮性卵巢癌miR-212相对表达量(0.842±0.223)显著低于癌旁卵巢组织(1.212±0.438)。miR-212在Ⅲ/Ⅳ期中相对表达量为(0.865 3±0.469 3),明显低于I/Ⅱ期(1.095 2±0.415 2)（P<0.05)。在低分化癌组织中相对表达量为(0.856 0±0.437 6),明显低于中高分化癌组织(1.131 9±0.471 2)（P<0.05)。而且miR-212在有淋巴结转移组相对表达量为(0.879 4±0.462 2),明显低于无淋巴结转移组（1.163 7±0.412 7)（P<0.01)。但与患者年龄（P=0.430）,肿瘤组织学类型（P=0.546）无关。miR-212转染组SKOV3细胞运动、侵袭均低于未转染组,miR-212转染组抑制SKOV3细胞Vimentin表达,但促进E-cadherin表达。结论:卵巢癌中miR-212低表达,miR-212表达缺失可能与卵巢癌的肿瘤生长和侵袭发展相关,在卵巢癌预后判断中可能有一定价值。     

Diagnostic and prognostic implications of microRNAs in human hepatocellular carcinoma

MicroRNAs (miRNAs) are important gene regulators, which are often deregulated in cancers. In this study, the authors analyzed the microRNAs profiles of 78 matched cancer/noncanerous liver tissues from HCC patients and 10 normal liver tissues and found that 69 miRNAs were differentially expressed between hepatocellular carcinoma (HCC) and corresponding noncancerous liver tissues (N). Then the expressions of 8 differentially expressed miRNAs were validated by real time RT PCR. The set of differentially expressed miRNAs could distinctly classify HCC, N and normal liver tissues (NL). Moreover, some of these differentially expressed miRNAs were related to the clinical factors of HCC patients. Most importantly, Kaplan-Meier estimates and the log-rank test showed that high expression of hsa-miR-125b was correlated with good survival of HCC patients (hazard ratio, 1.787, 95% confidence interval, 1.020-3.133, p = 0.043). The transfection assay showed that overexpression of miR-125b in HCC cell line could obviously suppress the cell growth and phosporylation of Akt. In conclusion, the authors have demonstrated the diagnostic miRNA profile for HCC, and for the first time, identified the miR-125b with predictive significance for HCC prognosis.     

The expression and prognostic value of REXO4 in hepatocellular carcinoma

BackgroundGlobally, one of the dominant causes of cancer-related mortality is liver cancer. Identification of potent biomarkers for initial stage diagnosis and prognosis is a key factor to ensure efficient therapy and reduce the mortality rate in liver cancer patients. REXO4 has been reported in neuropathic pain and familial isolated pituitary adenoma (FIPA), however, its relationship with liver cancer is still elusive.MethodsIn an attempt to scrutinize the expression of REXO4 in liver cancer, the Oncomine, and TCGA databases were analyzed. Real-time PCR was employed to identify the REXO4 mRNA levels in 45 patient tissue samples and western blot was used to detect the REXO4 protein levels in hepatocellular carcinoma (HCC) cells. Evaluation of the prognostic value of REXO4 in liver cancer was made using Univariate and multivariate Cox proportional hazards regression models and Kaplan–Meier plots. Tumor‐associated biological processes related to REXO4 were revealed by LinkedOmics. The correlation of REXO4 and immune infiltration was evaluated using the TIMER database.ResultsREXO4 is significantly up-regulated in liver cancer in comparison with the nontumor controls. Moreover, poor progression-free survival and overall survival is a frequent outcome related to high expression of REXO4, highlighting it as a risk factor in case of liver cancer. Additionally, the plausible role of REXO4 in tumor-immune interactions was also investigated and it was revealed that the immune infiltration and immune activation of liver cancer might have an association with REXO4.ConclusionsREXO4 has a significant expression in liver cancer and could potentially become a predictor for the prognosis of liver cancers and a biomarker for targeted therapeutic regimens. Significant overexpression of REXO4 in HCC was revealed by the bioinformatics analysis, with REXO4 overexpression being related to a negative outcome in HCC patients, in addition, REXO4 might be associated with the immune infiltration in liver cancer. Such a vital understanding of the functioning of REXO4 may furnish a foundation for new targeted drug therapy as well as a new direction for additional investigation into the underlying mechanisms of REXO4 carcinogenesis in liver cancer.     

三维能量多普勒超声检测宫颈癌的血流与 miR -455 表达的相关性研究

目的：探讨经阴道三维能量成像（3D—CPA）检测宫颈癌的血流与miR-455相对表达量的关系。方法：采用实时荧光定量PCR技术检测68例宫颈癌和49例慢性宫颈炎组织中miR-455的表达。用3D—CPA成像对宫颈血流进行检测并计算血管指数（VI）,最后进行比较分析。结果：慢性宫颈炎组宫颈血流不丰富,VI为（0．439±0．181）条／cm3;宫颈癌组宫颈血流丰富、杂乱,VI为（0．940±0．447）条／cm3。宫颈癌组VI高于慢性宫颈炎组,P〈0．01。宫颈癌组织内miR-455的表达量低于慢性宫颈炎组（1．174-0．59VS2．58±0．83,P〈0．01）。宫颈癌组织内miR-455的表达水平与VI呈负相关（r=-0．295,P=0．014）。结论：miR-455低表达可能促进宫颈癌的血管生成,是一个潜在的抑癌基因。