目的 探讨TRIB2在结肠癌中的表达水平及与预后及免疫浸润之间的关系。方法 TIMER数据库分析TRIB2在泛癌种中的表达;TCGA、GSE17538下载结肠癌患者RNA-seq数据和临床信息,评估其与临床病理特征的相关性;生存曲线、单因素和多因素Cox分析探讨TRIB2与预后的相关性,并构建列线图;对TRIB2进行差异基因的富集分析;分析TRIB2表达水平与免疫细胞浸润、免疫检查点、肿瘤突变负荷（TMB）以及免疫治疗敏感性之间的相关性。结果 TRIB2在结肠癌组织中高表达（P<0.05）;CMS1结肠癌患者TRIB2 mRNA表达水平最高;TRIB2是结肠癌患者的独立预后因素（单因素Cox回归分析：HR=1.397,95%CI：1.100~1.774,P=0.006;多因素Cox回归分析：HR=1.502,95%CI：1.158~1.947,P=0.002）;TRIB2与免疫细胞的浸润密切相关,并且与免疫检查点分子表达水平以及TMB正相关（r=0.39,P<0.001）;TRIB2的表达水平与免疫检查点抑制剂的疗效相关。结论 TRIB2在结肠癌中高表达且与结肠癌患者预后差和免疫微环境密切相关。

Objective To explore the expression of TRIB2 in colon cancer and its relationship with prognosis and immune cell infiltration. Methods TIMER database was used to analyse the expression of TRIB2 in pan-cancer．RNA-seq data and clinical information of colon cancer patients were downloaded from TCGA and GSE17538 to assess the correlation between TRIB2 with clinicopathological features．Survival curves,univariate and multivariate COX regression analysis were performed to explore the correlation between TRIB2 and prognosis,and a nomogram was constructed．Gene enrichment analyses were performed for TRIB2．Correlations between TRIB2 expression and immune cell infiltration,immune checkpoints,tumor mutation burden（TMB）,and immunotherapy sensitivity were analyzed．Results TRIB2 was highly expressed in colon cancer tissues（P<0.05）．The highest level of TRIB2 mRNA expression was found in CMS1．TRIB2 was an independent prognostic factor for colon cancer patients（univariate Cox regression analysis：HR=1.397,95%CI：1.100-1.774,P=0.006;multivariate Cox regression analysis：HR=1.502,95%CI：1.158-1.947,P=0.002）．TRIB2 was closely associated with immune cell infiltration and positively correlated with the expression level of immune checkpoint molecules as well as TMB（r=0.39,P<0.001）．The expression of TRIB2 was correlated with the efficacy of immune checkpoint inhibitors．Conclusions TRIB2 is highly expressed in colon cancer and is closely associated with poor prognosis and the immune microenvironment of colon cancer patients．

目的 通过多种生物信息学方法分析MAML1在GC患者中的表达及与临床特征、预后和免疫治疗疗效的相关性。方法 利用TCGA数据库分析胃癌组织与正常胃黏膜组织中的MAML1表达水平;Kaplan-Meier在线工具对胃癌数据集GSE15459进行分析,阐明MAML1与患者临床特征及分期、治疗疗效的相关性;STRING软件预测与MAML1表达相关的基因,并用FUNRICH软件评估其富集的分子生物学功能和信号通路;TIMER和GEPIA数据库探索MAML1表达水平与肿瘤浸润免疫细胞及其相应基因标记集之间的关系。结果 MAML1在GC组织中的表达水平高于正常组织(P<0.001),且其表达水平与III期、有淋巴结转移、无远处转移的患者生存期相关(P<0.05),而与I、II和IV期、无淋巴结转移和有远处转移的患者生存期无相关性(P>0.05)。MAML1的相关作用基因主要分布在细胞核、参与转录调控,并且主要富集在雄激素受体、C-MYB转录因子和HIF-2α转录调控等相关的信号通路。MAML1表达水平与B细胞、CD4⁺ T细胞、巨噬细胞的表达水平存在正相关关系(P<0.05),但与肿瘤纯度、CD8⁺ T细胞、中性粒细胞、树突状细胞无相关性(P>0.05)。结论 MAML1有可能成为GC患者较差的临床预后标志物之一,其潜在分子机制可能与转录调控调节肿瘤微环境有关。

Objective To investigate the expression of MAML1 and its relationship with clinical characteristics, prognosis and the efficiency of immunotherapy in patients with GC. Methods MAML1 expression profile was observed by TCGA database. Kaplan-Meier survival analysis was applied to evaluate the correlation between the expression of MAML1 and clinical characteristics, prognosis and treatment efficiency of patients in GSE15459 dataset. MAML1-associated genes were predicted by STRING and were enriched in GO and KEGG by FUNRICH software. The relationship between MAML1 expression and markers of tumor infiltrated cells were explored by TIMER and GEPIA database. Results MAML1 was abnormally upregulated in GC tissues compared to normal gastric tissues (P<0.001). MAML1 expression was significantly associated with the overall survival of patients in stage III, with lymph node metastasis and without distant metastasis (P<0.001). There was no significant difference between MAML1 expression and the overall survival of patients in stage I, II, IV, without lymph node metastasis and with distant metastasis (P>0.05). MAML1-assoicated genes were mainly located at the nucleus, mediating transcriptional regulation and mainly enriching in androgen receptor, C-MYB transcription factor and HIF-2α transcription regulation and other related signaling pathways. MAML1 expression was positively related with the expression of B cell, CD4⁺ T cell and macrophages (P<0.05), but without significant difference with tumor purity, CD8⁺ T cell, neutrophils and dendritic cells (P>0.05). Conclusions MAML1 could be used as a marker of clinical prognosis of patients with GC. The potential molecular mechanism might be associated with its function in transcriptional regulation and changes in tumor microenvironment.

目的 乳腺癌是世界范围内最常见的恶性肿瘤之一。目前,人们对乳腺癌的发病机制进行了大量的研究,但对其分子机制的认识尚不清楚。本研究采用生物信息学技术,筛选乳腺癌潜在的关键基因,最终为乳腺癌的诊断、治疗及预后判断提供潜在的生物标记物。方法 从基因表达综合数据库(GEO)下载基因芯片GSE36295、GSE71053和GSE86374,通过GEO2R鉴定差异表达基因(DEGs),并进行功能富集分析。利用STRING构建了蛋白质-蛋白质相互作用网络(PPI),并采用Cytoscape进行了模块分析。结果 共鉴定出95个DEGs,包括62个上调基因和33个下调基因。共鉴定出10个Hub基因:CENPF、KIF2C、TOP2A、NUSAP1、HMMR、MELK、KIF4A、ASPM、CEP55、CCNB1。结论 本研究发现的Hub基因可能对乳腺癌的发展和预后存在一定影响,为乳腺癌的诊断和治疗提供候选靶点。

Objective Breast cancer is one of the most common cancers worldwide. At present, a lot of researches have been carried out on the pathogenesis of breast cancer, but the molecular mechanisms of breast cancer are still not well understood. In this study, bioinformatics technology was used to screen the potential key genes of breast cancer, and ultimately to provide potential biomarkers for the diagnosis, treatment and prognosis of breast cancer. Methods The microarray datasets GSE36295、GSE71053和GSE86374 were downloaded from Gene Expression Omnibus (GEO), and the differentially expressed genes (DEGs) were identified by GEO2R, and the enriched functions and pathways of the DEGs were analyzed. Protein-protein interaction network (PPI) was constructed by using String, and the module analysis was performed using Cytoscape. Results A total of 95 DEGs were identified, consisting of 62 upregulated genes and 33 downregulated genes.Ten hub genes were identified: CENPF,KIF2C,TOP2A,NUSAP1,HMMR,MELK,KIF4A,ASPM,CEP55,CCNB1. Conclusion The hub gene was found in this study may be involved in the development and prognosis of breast cancer. It may provide candidate targets for diagnosis and treatment of breast cancer.

目的 通过生物信息学方法,分析阿司匹林抗结直肠癌的作用机制。方法 在DrugBank 5.1.5中查找阿司匹林的直接作用蛋白靶点(direct protein targets,DPTs);构建阿司匹林DPTs的蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络并分析相关信号通路;从GEO数据库中获取结直肠癌表达谱芯片数据,筛选中心度最高的20个结直肠癌差异表达基因作为Hub基因;将DPTs相互关联基因与结直肠癌Hub基因求交集,确认阿司匹林抗结直肠癌的潜在作用靶点,分析其在TCGA数据库结肠腺癌样本中的表达情况,并进行GO功能富集分析和KEGG信号通路分析。最终通过RT-PCR和WB实验验证阿司匹林抗结直肠癌的潜在靶点。结果 在DrugBank 5.1.5中确定了11个阿司匹林DPTs,KEGG信号通路分析发现其中6个DPTs(EDNRA,IKBKB,NFKB2,NFKBIA,PTGS2,TP53)与癌症的发生发展有关。将DPTs相关联基因与筛选的20个结直肠癌Hub基因求交集,发现5个基因(CDK1,AURKA,CCNB1,MAD2L1,TPX2)可能是阿司匹林抗结直肠癌的潜在作用靶点,其在TCGA数据库结肠腺癌样本中均表达上调,基因功能主要富集于细胞周期调控。RT-PCR和WB实验结果显示阿司匹林可以降低人结肠癌细胞中CDK1,AURKA,CCNB1,MAD2L1,TPX2的mRNA水平和蛋白表达。结论 CDK1,AURKA,CCNB1,MAD2L1,TPX2可能是阿司匹林抗结直肠癌的潜在靶点,其可能通过影响细胞周期调控发挥抗肿瘤作用。

Objective To analyze the mechanism of aspirin against colorectal cancer(CRC)by bioinformatic analysis. Methods DrugBank 5.1.5 was used to identify direct protein targets (DPTs) of aspirin. The protein-protein interaction (PPI) network of DPTs was constructed and involved signaling pathways were analyzed. CRC-associated gene expression datasets were downloaded from GEO database, and the top twenty differentially expressed genes with the highest degree were screened out as Hub genes. Common genes between the genes associated with the DPTs and the Hub genes of CRC were the potential targets of aspirin against CRC. The potential targets in TCGA database colon adenocarcinoma (COAD) samples were examined. GO functional enrichment analysis and KEGG signaling pathway analysis of the potential targets were performed. The potential targets of aspirin against CRC cells were verified by reverse transcription-polymerase chain reaction (RT-PCR) and western blot (WB). Results Eleven DPTs of aspirin were identified in DrugBank 5.1.5. KEGG signaling pathway showed that 6 genes (EDNRA, IKBKB, NFKB2, NFKBIA, PTGS2, TP53) were associated with the occurrence and development of CRC. By intersecting 20 Hub genes of CRC with genes associated with the DPTs of aspirin, it was found that 5 genes (CDK1, AURKA, CCNB1, MAD2L1, TPX2) might be the potential targets of aspirin against CRC. They were all up-regulated in TCGA-COAD samples, and the gene functions were mainly enriched in cell cycle regulation. The results of RT-PCR and WB showed that aspirin could down-regulate the mRNA and protein expression levels of CDK1, AURKA, CCNB1, MAD2L1 and TPX2 in human colon cancer cells respectively. Conclusion CDK1, AURKA, CCNB1, MAD2L1 and TPX2 could be potential targets of aspirin against CRC by affecting the progress of cell cycle regulation.

目的 利用GEPIA数据库,包括TCGA数据库和GTEX数据库,探讨二氢丹参酮I通过氧化应激治疗胃癌的潜在靶点。方法 在数据库中检索二氢丹参酮I在胃癌中潜在靶点的文献,利用GEPIA数据库工具分析二氢丹参酮I在胃癌中的潜在作用机制,分析潜在靶基因与表达关键抗氧化应激蛋白基因的相关性;二氢丹参酮I对胃癌潜在靶基因表达水平的分析;二氢丹参酮I对胃癌潜在靶基因的预后分析。结果 二氢丹参酮I对潜在靶基因的主要靶向基因(蛋白)为缺氧诱导因子-1(hif-1)和瓜氨酸组蛋白h3(cith3),其基因分别为HIF1 A和NOS2;GEPIA数据库显示HIF1 A与CAT(P=e-04,r=0.18)、GPX1(P=0.033,r=0.11)或NFE2L2呈正相关。(P=0,r=0.41),而NOS2与SOD1仅呈正相关(P=0.21,r=0.18),与其它三个基因均无相关性;HIF1 A和NOS2在胃癌组织中的表达水平高于正常胃旁组织;HIF1 A的高表达降低了胃癌患者的总生存率。结论 二氢丹参酮I可通过活性氧介导的氧化应激诱导AGS细胞凋亡,抑制HIF1 A和NOS2的表达,从而抑制AGS细胞的抗氧化应激,提高胃癌患者的总生存率。

Objective In this study, GEPIA database, including TCGA database and GTEx database, were used to explore the potential targets of dihydrotanshinone I on gastric cancer through oxidative stress. Methods Literatures on potential targets of dihydrotanshinone I in gastric cancer were searched in the database;GEPIA database tool was used to analyze the potential mechanism of dihydrotanshinone I on gastric cancer;taking analysis of the correlation between potential target genes and genes expressing key antioxidant stress proteins;We had analysis of expression level of dihydrotanshinone I on potential target genes in gastric cancer patients;and prognostic analysis of dihydrotanshinone I on potential target genes in gastric cancer patients. Results The main targeting genes(proteins) of dihydrotanshinone I on potential target genes were hypoxia inducible factor-1(hif-1) and citrulline histone H3(CITH3), whose genes were HIF1 A and NOS2, respectively;GEPIA database showed that there was a positive correlation between HIF1 A and CAT(P=2e-04, R=0.18), GPX1(P=0.033, R=0.11), or NFE2L2(P=0, R=0.41), while NOS2 only had a positive correlation with SOD1(P=0.21, R=0.18), and no correlation with other three genes. The expression levels of HIF1 A and NOS2 in gastric cancer tissues were higher than those in normal adjacent gastric tissues. The overall survival rate of patients with gastric cancer decreased with the high expression of HIF1 A. Conclusion Dihydrotanshinone I may induce apoptosis of AGS cells through reactive oxygen species mediated oxidative stress, and inhibit the expression of HIF1 A and NOS2, thus inhibit their antioxidative stress, which may improve the overall survival rate of gastric cancer patients.

目的 采用生物信息学方法预测低氧预处理人胎盘绒毛膜间充质干细胞环状RNAs相对应的miRNA及其靶基因,并分析靶基因所参与的生物学过程和信号通路。方法 用Arraystar公司的商业软件为环状RNAs预测其相对应的miRNAs,分别用targetScan7.1和mirdbV5数据库预测miRNAs的靶基因,并取两个预测结果的合集,应用在线网站http://www.geneontology.org和http://www.genome.ad.jp/kegg对靶基因进行功能富集分析和信号通路富集分析。结果 功能富集分析表明,circRNAs的靶基因主要涉及到细胞发育、细胞分化和细胞发育调控。东京基因和基因组百科全书信号通路富集分析表明肿瘤中转录失控和有丝分裂原激活蛋白激酶(MAPK)信号通路最有意义,而且分析发现MAPK信号通路为核心通路。本研究表明,低氧预处理使得间充质干细胞中部分circRNAs的表达量发生差异性变化。结论 低氧预处理人胎盘绒毛膜间充质干细胞环状RNAs同低氧预处理间充质干细胞的生物学特性变化密切有关,为了解低氧预处理影响间充质干细胞特性发生变化的分子机制提供新思路。

Objective To predict the miRNA and its target genes of circular RNAs in hypoxia- preconditioned human palcenta chorionic mesenchymal stem cells using bioinformatics, and analyze the biological process and signaling pathway. Methods Arraystar's commercial software was used to predict the corresponding miRNAs of circular RNAs. The target genes of miRNAs were predicted by targetScan7.1 and mirdbV5 databases respectively, and an intersection of two prediction results was obtained. The online databases http://www. geneontology.org and http://www.genome.ad.jp/kegg performed functional enrichment analysis and signal pathway enrichment analysis of target genes. Results Functional enrichment analysis indicated that the target genes of circRNAs mainly involved cell development, cell differentiation and cell development regulation. The signal enrichment analysis of the Tokyo Gene and Genome Encyclopedia indicates that transcriptional misregulation in cancer and mitogen-activated protein kinase (MAPK) signaling pathway are most meaningful, and the MAPK signaling pathway is found to be the core pathway. This study showed that hypoxic preconditioning caused significant changes in the expression of mesenchymal stem cell circRNAs. Conclusion The changes of circular RNAs in hypoxia-preconditioned human placental chorionic mesenchymal stem cell is closely related to the biological characteristics of hypoxia-preconditioned mesenchymal stem cells. This study provides a new idea for understanding the molecular mechanism of hypoxic preconditioning affecting the changes of biological characteristics in mesenchymal stem cells.

目的 通过生物信息分析途径,从分子水平揭示非酒精性脂肪性肝病（NAFLD）的发病发展机制,为NAFLD研究提供新的思路。方法 从公共数据库GEO中下载NAFLD相关的基因芯片数据GSE48452,利用Transcriptome Analysis Console软件筛选差异表达基因,FunRich软件和STRING在线分析工具对差异基因进行下一步的生物信息学分析。结果 正常组与NAFLD组差异基因52个,正常组与非酒精性脂肪性肝炎（NASH）基因64个,共同差异基因15个。这些差异表达基因参与脂质转运、胆汁酸合成、脂质和脂蛋白代谢、生物氧化等过程。通过通路分析及蛋白质相互作用分析进一步筛选出与NAFLD发病发展密切相关的18个差异表达基因。结论 通过生物信息学分析筛选出MSN、CDC45、ANXA5、PIK3CG和DTL基因可能为研究乃至阻断NAFLD发展进程的重要靶点,需进一步验证。

Objective To explore the molecular mechanism of nonalcoholic fatty liver disease （NAFLD） with bioinformatics analysis. Methods The microarray data of NAFLD were downloaded from the Gene Expression Omnibus （GEO） database and analyzed using Transcriptome Analysis Console （TAC） for screening differentially expressed genes. The further analysis of differentially expressed genes was conducted by FunRich software and the online tool STRING. Results For the comparison of control group vs. NAFLD group,52 genes have differentially expressed,while control groups vs. nonalcoholic steatohepatitis （NASH） group,64 genes have differentially expressed. 15 differentially expressed genes were found in both comparisons. These genes were involved in the biological pathway of lipid transport,bile acid biosynthesis,metabolism of lipids and lipoproteins and biological oxidations. With biological pathway analysis and protein-protein interaction analysis,18 differentially expressed genes were found closely associated with the progression of NAFLD. Conclusion MSN、CDC45、ANXA5、PIK3CG and DTL may be the important target for study the progression of NAFLD,which needs a further study to confirm.

       目的  探讨TRIB2在结肠癌中的表达水平及与预后及免疫浸润之间的关系。方法  TIMER数据库分析TRIB2在泛癌种中的表达；TCGA、GSE17538下载结肠癌患者RNA-seq数据和临床信息，评估其与临床病理特征的相关性；生存曲线、单因素和多因素Cox分析探讨TRIB2与预后的相关性，并构建列线图；对TRIB2进行差异基因的富集分析；分析TRIB2表达水平与免疫细胞浸润、免疫检查点、肿瘤突变负荷（TMB）以及免疫治疗敏感性之间的相关性。结果  TRIB2在结肠癌组织中高表达（P＜0.05）；CMS1结肠癌患者TRIB2 mRNA表达水平最高；TRIB2是结肠癌患者的独立预后因素（单因素Cox回归分析：HR=1.397，95%CI：1.100~1.774，P=0.006；多因素Cox回归分析：HR=1.502，95%CI：1.158~1.947，P=0.002）；TRIB2与免疫细胞的浸润密切相关，并且与免疫检查点分子表达水平以及TMB正相关（r=0.39，P＜0.001）；TRIB2的表达水平与免疫检查点抑制剂的疗效相关。结论  TRIB2在结肠癌中高表达且与结肠癌患者预后差和免疫微环境密切相关。

       Objective  To explore the expression of TRIB2 in colon cancer and its relationship with prognosis and immune cell infiltration．Methods  TIMER database was used to analyse the expression of TRIB2 in pan-cancer．RNA-seq  data and clinical information of colon cancer patients were downloaded from TCGA and GSE17538 to assess the correlation between TRIB2 with clinicopathological features．Survival curves，univariate and multivariate COX regression analysis were performed to explore the correlation between TRIB2 and prognosis，and a nomogram was constructed．Gene enrichment analyses were performed for TRIB2．Correlations between TRIB2 expression and immune cell infiltration，immune checkpoints，tumor mutation burden（TMB），and immunotherapy sensitivity were analyzed．Results  TRIB2 was highly expressed in colon cancer tissues（P＜0.05）．The highest level of TRIB2 mRNA expression was found in CMS1．TRIB2 was an independent prognostic factor for colon cancer patients（univariate Cox regression analysis：HR=1.397，95%CI：1.100-1.774，P=0.006；multivariate Cox regression analysis：HR=1.502，95%CI：1.158-1.947，P=0.002）．TRIB2 was closely associated with immune cell infiltration and positively correlated with the expression level of immune checkpoint molecules as well as TMB（r=0.39，P＜0.001）．The expression of TRIB2 was correlated with the efficacy of immune checkpoint inhibitors．Conclusions  TRIB2 is highly expressed in colon cancer and is closely associated with poor prognosis and the immune microenvironment of colon cancer patients．