基于TCGA数据库分析ASPM在肺腺癌中的表达及临床意义

目的：探讨异常纺锤体样小头畸形相关基因（ASPM）在肺腺癌中的表达水平，及其与患者临床病理指标和预后的关系。方法：从癌症基因组图谱（TCGA）数据库下载肺腺癌组织和癌旁组织mRNA表达水平和临床病例资料，比较ASPM mRNA在癌组织和癌旁组织中的表达差异，统计学分析ASPM表达水平与肺腺癌患者临床病理指标及预后关系。通过R语言ballgown和ggplot包筛选高低表达ASPM组间差异基因并绘制火山图；利用DAVID工具对差异基因进行GO分析，采用GSEA预测ASPM可能调控的信号通路；STRING和Cytoscape分析关键基因及差异表达基因间的相互作用。结果：ASPM mRNA在肺腺癌中表达水平显著高于癌旁组织（P < 0.05）；ASPM表达水平与生存期相关，高表达ASPM肺腺癌患者预后较差（P < 0.05），是肺腺癌患者预后的独立危险因素，R语言ballgown包筛选出ASPM高低表达组间的差异表达基因共183个，差异表达基因富集到生物过程（BP）、细胞组分（CC）、分子功能（MF）在3个类别共19个亚类和18条KEGG通路；Cytoscape软件发现4个枢纽蛋白。结论：ASPM mRNA在肺腺癌患者中呈高表达且高表达组预后差，可作为判断肺腺癌预后的标志物。     

基于TCGA数据库分析ASPM在肺腺癌中的表达及临床意义

目的：探讨异常纺锤体样小头畸形相关基因（ASPM）在肺腺癌中的表达水平,及其与患者临床病理指标和预后的关系。方法：从癌症基因组图谱（TCGA）数据库下载肺腺癌组织和癌旁组织mRNA表达水平和临床病例资料,比较ASPM mRNA在癌组织和癌旁组织中的表达差异,统计学分析ASPM表达水平与肺腺癌患者临床病理指标及预后关系。通过R语言ballgown和ggplot包筛选高低表达ASPM组间差异基因并绘制火山图;利用DAVID工具对差异基因进行GO分析,采用GSEA预测ASPM可能调控的信号通路;STRING和Cytoscape分析关键基因及差异表达基因间的相互作用。结果：ASPM mRNA在肺腺癌中表达水平显著高于癌旁组织（P < 0.05）;ASPM表达水平与生存期相关,高表达ASPM肺腺癌患者预后较差（P < 0.05）,是肺腺癌患者预后的独立危险因素,R语言ballgown包筛选出ASPM高低表达组间的差异表达基因共183个,差异表达基因富集到生物过程（BP）、细胞组分（CC）、分子功能（MF）在3个类别共19个亚类和18条KEGG通路;Cytoscape软件发现4个枢纽蛋白。结论：ASPM mRNA在肺腺癌患者中呈高表达且高表达组预后差,可作为判断肺腺癌预后的标志物。     

基于竞争内源性RNA网络探讨槲皮素在肺腺癌中的作用靶点

目的:利用从肺腺癌（LUAD）数据集中筛选的差异表达基因（DEGs）、差异表达lncRNA（DElncRNA）及其上游miRNA,构建LUAD的竞争内源性RNA网络（ceRNA）,探索槲皮素可能的作用靶点。方法:从基因表达综合数据库（GEO）及肿瘤基因组图谱数据库（TCGA）中检索并筛选LUAD基因及lncRNA表达数据集,对差异表达基因（DEGs）进行富集和功能注释。使用在线数据库预测miRNA及lncRNA,建立ceRNA调控网络,并通过网络药理学分析槲皮素的药物靶点。结果:构建了AURKA与上游hsa-miR-363-3p及AP000553.1、LINC00858、AL354707.1的ceRNA调控网络,槲皮素与5DOS对接良好。结论:AP000553.1、LINC00858、AL354707.1与hsa-miR-363-3p竞争性调控AURKA,进一步影响LUAD预后,槲皮素可作用于AURKA。     

Influence factors to recurrence of hepatocellular carcinoma after surgical resection

Duetomanyreasons,therecurrenceofhepatocellularcarcinoma(HCC)aftersurgicalresectioniseasilytakenplace.Thefocusofrecurrencecannotbere-resectedforthegreatpartofthepateints.Thetreatmentoftranscatheterarterialchemoembolization(TAE)wasperformedforthesepatients.Howtodecreasetherecurrencerateandincreasesurvivalrateofthesepatientsisoneofimportantproblems.Thecurrentstudywasestablishedtofindtherelationshipwithprimaryhepatocellularcarcinomaandrecurrencetumors,bysurgicalresectionfindings,pathologicalexa…     

肝癌术后复发原因的探讨

OBJECTIVE: To analyze the causes of recurrence of hepatocellular carcinoma (HCC) after resection according to pathologic findings of the resected primary tumor and angiographic features of the recurrent tumor. METHODS: In this series, 142 cases with recurrent HCC were analyzed with respect to (1) size, number, gross and histologic findings of the primary tumor, (2) time when recurrence occurred, (3) size, number, blood supply, staining property of, and deposition of lipiodol oil in the recurrent tumor. Following angiography, arterial embolization was performed. RESULTS: In 101 of the 142(71.1%) cases, the primary tumor was > 5 cm in diameter, and in 41 cases (28.9%) it was < 5 cm. In 67.7% of the cases, the capsule of the primary tumor was incomplete or absent. In 47 cases (33.1%), satellite tumor nodules were seen during operation but they were seen on pathologic sections in 94 cases (66.2%). Tumor thrombus was present in the portal vein in 26 (18.3%) and 121 cases (85.2%) during operation and on pathologic examination, respectively. In the majority of the cases (99/142), recurrence occurred within 6 months after operation. The recurrent foci consisted of multiple tumor nodules of < 5 cm in 68.3% of the cases. On angiography, the recurrent tumors were rich in blood supply with good deposition of lipiodol. CONCLUSION: Recurrence is apt to occur in HCC patients with large (> 5 cm) primary tumor which has incomplete or no capsule, satellite tumor nodules and portal vein tumor thrombus. It is suggested to perform angiography 1-2 months after surgery to detect early recurrence and, if confirmed, the patients can be treated by transcatheter arterial chemo-embolization.     

Morphometric evaluation of tumor matrix metalloproteinase 9 predicts survival after surgical resection of adenocarcinoma of the lung.

PURPOSE: Recently, several matrix metalloproteinases (MMPs) have shown promise as prognosticators in non-small cell lung cancer. In this study, we sought to validate the importance of MMP-9 and to study the relationships between MMP-9 and several other tumor or stromal markers. Experimental Design: We examined MMP-9 and several other markers in tumor tissues from 152 patients with surgically excised adenocarcinomas of the lung. Their preoperative clinical stages were T(1-4)N(0)M(0); however, pathological exam of their resected tissues demonstrated that 33 were stage II, and 64 were stage III. We used immunohistochemistry and morphometry to evaluate the amount of tumor staining for MMP-9, and the outcome for our study was survival time until death from recurrent lung cancer. RESULTS: Multivariate Cox model analysis demonstrated that pathological stage was significantly related to survival time (P < 0.01), but quantitative staining of the tumor for MMP-9 added prognostic information (P < 3.0 x10(-16)) and was more strongly prognostic than pathological stage. In the subset of pathological stage I patients, staining for MMP-9 was also significantly associated with survival (P < 1.0 x10(-6)), and a cutpoint at the median staining of 11.2% for MMP-9 divided them into two groups with distinctive survival times. Those with MMP-9 > 11.2% had a median survival time of just 11 months. Those with MMP-9 < 11.2% had not reached a median survival and had a mean survival time of >62 months. CONCLUSIONS: Tumor staining for MMP-9 in resected adenocarcinoma of the lung is strongly related to survival. Patients with >11.2% staining in their tumors comprise a subset with a high hazard for dying of lung cancer and may be an appropriate target for prospective studies of adjuvant chemotherapy after surgical resection.     

Usefulness of urinary NMP22 to detect tumor recurrence of superficial bladder cancer after transurethral resection

Background In a prospective study we compared the usefulness of urinary nuclear matrix protein 22 (NMP22) with that of urine cytology and other urinary markers in the monitoring of superficial bladder cancer after transurethral resection (TURBT).Methods The subjects were 156 patients, comprising 99 patients with superficial bladder cancer in whom TURBT was planned (untreated group) and 57 patients without tumors in the bladder who had been followed up after TURBT (follow-up group).Results Among the 156 patients, who were monitored for 11–26 months (median, 21 months), recurrence was observed in 51 patients (33.0%). At the time of recurrence, the sensitivities of NMP22, basic fetoprotein (BFP), and bladder tumor antigen (BTA) tests, and urine cytology were 18.6%, 23.3%, 9.3%, and 7.0%, respectively. The factors affecting the sensitivity of NMP22 were tumor size and urinary WBC. The size of recurrent tumors was significantly smaller (P 0.05) than that of the initial tumors. Based on receiver operating characteristic (ROC) curves calculated from the data of patients with recurrence, the ideal cutoff values at recurrence were recommended to be 5.0U/ml for NMP22 and 6.0ng/ml for BFP. Using these cutoff values, the sensitivities of NMP22 and BFP were 48.8% and 44.2%, respectively.Conclusions Because the size of recurrent bladder tumors is usually smaller than that of the initial tumors, the cutoff values of urinary markers should be reduced to detect these tumors. We recommend 5.0U/ml as a cutoff value of NMP22 for detection of recurrence of bladder tumor.     

Solid predominant subtype in lung adenocarcinoma is related to poor prognosis after surgical resection: A systematic review and meta-analysis

BackgroundRecent studies have indicated that solid predominant (SP) subtype of lung adenocarcinoma (LADC) may be associated with early recurrence and worse prognosis. Hence, a systematic review and meta-analysis were performed to evaluate the association between LADC subtype and survival.MethodsThe MEDLINE, SCOPUS, Web of Science and Cochrane Libraries were reviewed for eligible studies in December 2017. Studies were included if they compared outcomes of patients with and without SP subtype in resection specimens of LADC patients after surgical treatment by using multivariate Cox regression analysis. A meta-analysis for overall survival (OS) and disease-free survival (DFS) was performed. The hazard ratios (HR) or odds ratios with 95% confidence intervals (CIs) from each study were used to calculate pooled HRs. Statistical analyses were performed using Review Manager 5.3.ResultsIn total, 14 eligible studies including 12,137 LADC patients were identified, which assessed the impact of SP subtype on OS and DFS in patients treated with pulmonary resection. SP subtype was reported in 1246 (10.2%) patients and was associated with significantly worse OS (pooled HR, 1.51; 1.29–1.75) and DFS (pooled HR, 1.26; 1.14–1.40).ConclusionsSP subtype is associated with significantly worse OS and DFS in patients with LADC after pulmonary resection. These data provide evidence for the integration of the distinct histological LADC subtyping into prognostic tools and guidelines for adjuvant treatment after complete surgical resection.     

短发夹RNA靶向沉默TPX2基因促进人肺腺癌A549细胞凋亡及其相关机制

目的:探讨靶向Xklp2靶蛋白(targeting protein for Xenopus kinesin-like protein2,TPX2)基因的短发夹RNA(short hairpin RNA,shRNA)对肺腺癌A549细胞凋亡的影响及其可能机制。方法:构建靶向TPX2基因的shRNA重组载体,将其转染至肺腺癌A549细胞中,RT-PCR检测细胞中TPX2、Aurora-A、p53和Bcl-2mRNA的表达,蛋白质印迹法检测TPX2蛋白的表达,FCM检测细胞周期和细胞凋亡情况。结果:成功构建重组载体pMagic4.1-shRNA-TPX2。将pMagic4.1-shRNA-TPX2转染至A549细胞后,TPX2、Aurora-A和Bcl-2mRNA的表达水平明显下调,p53mRNA的表达水平明显上调,TPX2蛋白的表达水平明显下调,细胞凋亡率明显增加,细胞阻滞于S期,与空白对照组(未转染组)和阴性对照组(转染pMagic4.1-shRNA-NC)相比,差异均有统计学意义(P<0.05)。结论:靶向TPX2的shRNA能促进肺腺癌A549细胞的凋亡,其作用可能与上调p53表达和下调Bcl-2表达有关。     

基于TCGA数据库分析E2F7在肾透明细胞癌组织中的表达及临床意义

目的:通过数据挖掘分析E2F7在肾透明细胞癌(clear cell renal cell carcinoma,ccRCC)组织中的表达特征及临床意义.方法:基于GEPIA、LinkedOmics数据库分析E2F7在ccRCC中的差异性表达及其与患者预后的关系.应用WebGestalt工具分析与E2F7表达相关的基因.结...     

siRNA抑制HER2/neu过表达肺腺癌细胞生长和增殖

背景与目的：30％NSCLC存在HER2／neu过表达，与肿瘤发生、转移、肿瘤血管形成、抗凋亡及化疗耐药等有关。本文通过RNA干涉抑制肺腺癌细胞SPC—A-1 HER2／neu过表达，观察肿瘤细胞周期、增殖及集落形成能力的变化。方法：构建针对HER2／neu的siRNA重组质粒，稳定转染SPC—A-1，通过RT—PCR和Western Blot检测HER2／neu表达；FCM分析细胞周期；MTT法观察细胞增殖，绘制细胞生长曲线；平板集落形成实验检测肿瘤细胞的集落形成能力。结果：成功构建了HER2／neu的siRNA重组质粒，稳定转染靶细胞后可显著降低HER2／neu表达；与亲代细胞相比，G0／G1期细胞增加17．1％，S期细胞减少12．8％；细胞生长速度减慢，集落S1抑制率达到49．0％。结论：针对HER2／neu的siRNA可以显著降低肺腺癌细胞过表达HER2／neu，肿瘤细胞阻滞于G0／G1期，造成细胞增殖减慢，集落形成能力明显下降。因此，siRNA对过表达HER2／neu肺癌的治疗具有潜在应用价值。     

基于公共数据库分析NAT2基因在结肠癌组织中的表达及其与预后的相关性

目的:探讨N-乙酰化转移酶2（NAT2）基因在结肠癌组织中的表达及其与预后的相关性。方法:下载公共数据库中（Oncomine和TCGA）有关NAT2基因表达的数据集,利用在线平台进行数据挖掘,然后对NAT2在结肠癌中的作用进行荟萃分析。结果:Oncomine中检索到涉及NAT2基因的研究包含结肠癌446例和正常组织200例,TCGA中检索到涉及NAT2基因的研究包含结肠癌286例和正常组织41例。与正常结肠组织相比,在结肠癌中NAT2 mRNA的表达量显著降低（P＜0.01）。另外,免疫组化结果表明NAT2 在正常组织中呈较强或中等表达,而在结肠癌组织中则表达较弱或呈阴性。通过分析结肠癌患者的生存信息发现,NAT2基因低表达患者有着更高的死亡率,而高表达NAT2的患者则预后较好（P＜0.05）。结论:在结肠癌中,NAT2基因和蛋白均呈现低表达,并与结肠癌预后相关,有望发展为结肠癌新的诊断和治疗靶点。     

Diagnostic and prognostic potential of the novel biomarker nuclear cap binding protein subunit 2 (NCBP2) in colon adenocarcinoma

BackgroundColon adenocarcinoma (COAD) is an incurable malignancy and the third most common tumor worldwide. Advances in biomarkers screening have greatly contributed to explore the new diagnostic and prognostic biomarkers for the early detection and prognostic of COAD. However, the heterogeneity-specific nature of COAD in patients of different cancer stages, different races, genders and age are still the major challenge to clinical treatment.MethodsGene expression, copy number (CN), and dependency score (DS) data were obtained from the Cancer Cell Line Encyclopedia (CCLE), and linear regression analyses were performed using R language. We conducted receiver operating characteristic (ROC) curve analysis and compared the area under the ROC curve area under the curve (AUC) values to evaluate the sensitivity and specificity of nuclear cap binding protein subunit 2 (NCBP2) for the diagnosis of COAD in The Cancer Genome Atlas (TCGA) database. Survival analysis was performed in the distinct NCBP2 expression groups. In vitro experiments and bioinformatics analysis were used to investigate the molecular mechanisms of NCBP2 in COAD and its biological roles. A Connectivity Map (Cmap) was used to identify potential small molecule targeted drugs for NCBP2 in COAD.ResultsThrough the linear regression analysis of DS, CN, and gene expression, we determined that NCBP2 met our criteria. The mean AUC of the ROC curve of NCBP2 was 0.940±0.050. Survival analysis showed that high NCBP2 expression was associated with a worse prognosis [hazard ratio (HR) =1.98, P<0.007]. NCBP2 knockdown inhibited COAD cell proliferation and caused G0/G1 phase arrest in COAD cells.ConclusionsNCBP2 was the novel diagnostic and prognostic biomarker of in COAD. Our research had implications for the treatment of colon cancer.     

基于Oncomine和TCGA数据库分析E2F5在前列腺癌组织中的表达及临床意义

目的:通过数据挖掘分析E2F5在前列腺癌(PCa)组织中的表达及临床意义.方法:基于GEPIA、On-comine数据库分析E2F5在PCa中的差异性表达及其与预后的关系.高通量基因芯片筛选敲低E2F5差异表达的基因并应用Western blot验证.结果:E2F5 mRNA在PCa组织中表达明显高于正常前列腺组织(P...