CD39的临床意义及其与肝癌浸润T细胞耗竭的相关性分析

摘要 目的：探索CD39分子（编码基因ENTPD1）在原发性肝细胞肝癌（Hepatocellular carcinoma, HCC）中的表达、临床意义及其与HCC中免疫浸润和T细胞耗竭的相关性。方法：TIMER、GEPIA、Kaplan-Meier Plotter、TCGA等数据库分析CD39在肝癌中的差异性表达、与免疫浸润的关系、相关基因的表达及其与肝癌患者预后的关系。免疫荧光染色、细胞测序和流式检测验证临床HCC患者的癌及癌旁组织中CD39的差异性表达及其和CD8⁺T细胞耗竭特性的相关性。结果：（1）生物信息学分析结果显示：CD39在多种肿瘤组织中表达上调（包括HCC）（P＜0.05）；且其表达水平与HCC的临床预后等显著相关（P＜0.05）；与CD39低表达组相比，HCC中CD39高表达组患者无复发生存期（relapse-free survival, RFS）（P=0.025）和无进展生存期（progression-free survival, PFS）（P=0.026）较短；CD39与HCC肿瘤微环境中CD8⁺T、CD4⁺T、巨噬细胞等免疫细胞浸润水平均有明显正相关。（2）临床HCC样本验证：免疫荧光和流式结果显示CD39在癌组织中的表达水平高于癌旁正常组织，与耗竭相关分子LAYN、TIM3、CTLA4等共表达，且在耗竭CD8⁺T细胞中表达比例显著高于非耗竭细胞。结论：CD39在HCC肿瘤组织及浸润的CD8⁺T细胞中高表达，与HCC的RFS、PFS、免疫细胞浸润等紧密相关，且参与CD8⁺T细胞耗竭。     

SIRT7琥珀酰化修饰对肝癌生存、免疫浸润及预后的相关性分析

摘要 目的：探究SIRT7基因琥珀酰化修饰对肝癌患者的生存、免疫浸润及预后的相关性分析。方法：采用生物信息分析法对SIRT7在肝癌组织中的表达情况及其对肝癌患者预后的影响进行分析；采用蛋白免疫印迹法（Western blot）检测其转染效果。结果：（1）生物信息分析结果显示：SIRT7在多种肿瘤（包括肝癌）组织中呈高表达（P<0.05）；SIRT7的表达与肿瘤的生存曲线相关（P<0.05）；肝癌患者的SIRT7相对表达量与其预后相关，高表达组肝癌患者的总生存情况（P=0.017）和无进展生存情况较低表达组缩短（P=0.004）；免疫浸润和肿瘤微环境分析结果显示，SIRT7表达水平与多数免疫细胞浸润水平、肿瘤微环境(ESTIMATES core)均有明显负相关。（2）Western blot显示，SIRT7在肝癌细胞中表达高于正常细胞。因此，SIRT7 可作为肝癌的潜在预后标志物。结论：SIRT7表达水平与肝癌(HCC)患者的预后、免疫细胞浸润性、肿瘤微环境免疫细胞和基质细胞浸润等相关。     

肝细胞肝癌组织NTS、SPNS2、Mortalin表达与上皮间质转化标志物、临床病理特征和预后的关系

摘要 目的：探讨肝细胞癌（HCC）癌组织神经降压素（NTS）、鞘氨醇-1-磷酸转运体2（SPNS2）、热休克蛋白75（Mortalin）表达与上皮间质转化（EMT）标志物、临床病理特征和预后的关系。方法：选取2010年1月～2017年1月联勤保障部队第九〇〇医院仓山院区收治的90例HCC患者,采用免疫组化法检测患者癌组织和对应癌旁组织中NTS、SPNS2、Mortalin及EMT标志物N-钙粘蛋白（N-Cad）、E-钙粘蛋白（E-Cad）表达情况。分析NTS、SPNS2、Mortalin表达与HCC患者EMT标志物、临床病理特征和预后的关系。结果：HCC癌组织中NTS、SPNS2、Mortalin、N-Cad阳性表达率高于癌旁组织,E-Cad阳性表达率低于癌旁组织（P＜0.05）。Pearson相关性分析显示,HCC癌组织中NTS、SPNS2、Mortalin表达水平与N-Cad表达水平呈正相关,与E-Cad表达水平呈负相关（P＜0.05）。 HCC癌组织中NTS、SPNS2、Mortalin表达与Child-Pugh分级、血管侵犯、巴塞罗那临床肝癌（BCLC）分期、淋巴结转移、远处转移有关（P＜0.05）。90例HCC患者术后5年总生存率为48.89％（44/90）。Kaplan-Meier生存曲线分析显示,NTS、SPNS2、Mortalin阳性组总生存率分别低于NTS、SPNS2、Mortalin阴性组（P＜0.05）。结论：HCC癌组织中NTS、SPNS2、Mortalin表达上调,与EMT、Child-Pugh分级、血管侵犯、BCLC分期、淋巴结转移、远处转移和预后有关,可作为HCC病情及预后的辅助评估指标。     

基于生物数据挖掘分析PTX3在非小细胞肺癌中的表达及其与预后的关系

摘要 目的：探讨正五聚素蛋白 3（PTX3）在非小细胞肺癌（NSCLC）中的表达及预后意义。方法：运用 Oncomine、GEPIA分析PTX3在NSCLC组织中的表达情况，通过GEPIA分析PTX3表达与NSCLC患者生存期的相关性，利用CCLE分析 PTX3在 NSCLC细胞系中的表达水平，从CCLE下载NSCLC相关基因芯片并用 R语言筛选 PTX3共表达基因，利用基因本体（GO）和KEGG信号通路分析对 PTX3 相关共表达基因进行功能注释。结果：Oncomine和GEPIA 数据库中分析显示 PTX3 基因在NSCLC组织中显著低表达（P＜0.05）；利用GEPIA数据库生存分析功能发现，PTX3高表达与NSCLC预后呈负相关（P＜0.05）；在CCLE数据库里利用 R 软件共筛选出 105个NSCLC中与PTX3共表达的基因，GO功能富集分析表明，PTX3相关性蛋白主要定位于黏着斑、细胞-基质黏着连接及细胞间连接等，主要参与细胞外基质、细胞外结缔组织、细胞-基质粘附及上皮细胞发育等生物过程。KEGG分析显示PTX3共表达基因主要参与紧密连接、调节肌动蛋白骨架及JAK-STAT信号通路等。结论：PTX3基因在NSCLC组织中低表达，PTX3表达与NSCLC患者预后相关，可能作为NSCLC患者预后评估的分子标志物之一。     

非小细胞肺癌组织CENPF、KLF4表达与上皮-间质转化和预后的关系研究

摘要 目的：探讨非小细胞肺癌（NSCLC）组织中着丝粒蛋白F（CENPF）、Krüppel样因子4（KLF4）表达与上皮-间质转化（EMT）和预后的关系。方法：选取2017年1月至2019年12月期间于泰州市第四人民医院行手术切除的120例NSCLC患者的癌组织和距癌组织5cm癌旁组织标本,采用免疫组织化学法和免疫印迹法检测癌组织和癌旁组织中CENPF、KLF4及ETM相关标志物[E-钙粘蛋白（E-cadherin）、波形蛋白（Vimentin）]的阳性表达率和表达量。采用Pearson检验分析CENPF、KLF4与EMT相关标志物的相关性,并分析CENPF、KLF4表达与NSCLC患者预后的关系。结果：NSCLC癌组织中CENPF、Vimentin的阳性表达率显著高于癌旁组织（均P<0.05）,而KLF4、E-cadherin的阳性表达率均显著低于癌旁组织（均P<0.05）。NSCLC癌组织中CENPF与E-cadherin呈负相关,与Vimentin呈正相关（P<0.05）;而KLF4与E-cadherin呈正相关,与Vimentin呈负相关（P<0.05）。NSCLC癌组织中CENPF、KLF4的阳性表达率与TNM分期和淋巴结转移有关（均P<0.05）。入组患者3年无病生存率（DFS）为60.00%。CENPF阳性表达的NSCLC患者3年DFS显著低于CENPF阴性表达患者（56.25% vs 75.00%,P=0.014）,KLF4阳性表达的NSCLC患者3年DFS显著高于KLF4阴性表达患者（68.75% vs 54.17%, P=0.048）。结论：CENPF的高表达及KLF4的低表达可促进NSCLC的EMT发生、进展,并导致患者预后不良,CENPF和KLF4可辅助预测NSCLC患者的预后。     

肝细胞癌组织中OATP1B3的表达及其作用的初步研究

摘要 目的：探讨有机阴离子转运多肽1B3（OATP1B3）在肝细胞癌（肝癌）组织中的表达及作用。方法：通过免疫组化实验和免疫印迹试验（Western blot）检测肝癌组织及其癌旁组织中OATP1B3情况,并分析其与患者临床病理特征的相关性。采用实时荧光定量聚合酶链反应（qRT-PCR）检测OATP1B3在多株肝癌细胞中的表达情况,选择表达量相对较低的人肝癌细胞（HepG2和Huh7）细胞进行过表达实验,细胞毒实验（MTT）和流式细胞术分别检测OATP1B3对细胞增殖及凋亡的影响。结果：肝癌组织中OATP1B3表达水平明显低于癌旁组织（P<0.05）,且与患者恶性肿瘤国际临床病期分类（TNM分期）、肿瘤分化程度、有无肿瘤复发显著相关（P<0.05）。过表达OATP1B3可抑制HepG2和Huh7细胞增殖,促进细胞凋亡。结论：OATP1B3在肝癌组织中低表达,上调其表达可抑制肝癌细胞增殖和促进细胞凋亡。OATP1B3可能是肝癌的抑癌基因,对肝癌的发生、发展具有重要作用。     

下咽鳞状细胞癌组织claudin-1和MMP-9的表达及与临床病理特征及预后的关系研究

摘要 目的：研究下咽鳞状细胞癌组织紧密连接蛋白1（claudin-1）和基质金属蛋白酶-9（MMP-9）的表达及与临床病理特征及预后的关系。方法：选取2015年1月-2017年3月我院收集的75例下咽鳞状细胞癌组织标本进行研究,同期选取60例癌旁正常黏膜组织标本作为对照。采用免疫组织化学法检测claudin-1、MMP-9在下咽鳞状细胞癌组织与癌旁正常黏膜组织中的表达差异,分析claudin-1、MMP-9阳性表达与临床病理特征关系;Spearman相关性分析癌组织claudin-1与MMP-9的相关性。对患者进行5年随访,分析claudin-1、MMP-9表达与预后的关系。结果：下咽鳞状细胞癌组织claudin-1、MMP-9阳性表达率高于癌旁正常黏膜组织（P＜0.05）。claudin-1、MMP-9阳性表达与下咽鳞状细胞癌患者组织分化程度、淋巴结转移有关（P＜0.05）。经Spearman相关性分析显示,下咽鳞状细胞癌组织中claudin-1阳性表达与MMP-9阳性表达呈正相关（rs= 0.463,P＜0.05）。术后随访5年,2例失访,73例患者获得随访。Kaplan-Meier生存曲线显示,claudin-1阳性表达患者的5年生存率为35.71%,低于阴性表达患者的66.67%（P＜0.05）,MMP-9阳性表达患者的5年生存率为34.85%,低于阴性表达患者的57.14%（P＜0.05）。结论：下咽鳞状细胞癌组织中claudin-1、MMP-9阳性表达升高,其表达与组织分化程度、淋巴结转移和预后不良有关,两者呈正相关,可能发挥协同作用促进肿瘤发生发展。     

肌层浸润性膀胱癌组织KMT2D、MCM6与临床病理特征和预后的关系

摘要 目的：探讨肌层浸润性膀胱癌（MIBC）组织赖氨酸甲基转移酶2D（KMT2D）、微小染色体维持蛋白6（MCM6）与临床病理特征和预后的关系。方法：选择2017年5月至2019年10月长治医学院附属和平医院行手术治疗的MIBC患者96例,应用逆转录-实时定量聚合酶链式反应（qRT-PCR）检测癌组织及癌旁正常组织KMT2D 信使核糖核酸（mRNA）、MCM6 mRNA表达,分析KMT2D mRNA、MCM6 mRNA表达与MIBC患者临床病理特征的关系,应用Pearson相关分析法分析MIBC患者癌组织KMT2D mRNA及MCM6 mRNA表达的相关性。随访3年,比较死亡MIBC患者与存活MIBC患者癌组织KMT2D mRNA、MCM6 mRNA表达,并应用Kaplan-Meier生存曲线分析不同KMT2D mRNA、MCM6 mRNA表达分组MIBC患者预后情况。结果：MIBC癌组织中KMT2D mRNA表达水平显著低于癌旁组织,MCM6 mRNA表达水平显著高于癌旁组织（P<0.05）。MIBC患者癌组织中KMT2D mRNA、MCM6 mRNA表达与侵犯输尿管、淋巴结转移、TNM分期显著相关（P<0.05）,且两者表达呈负相关（P<0.05）。至随访截止,MIBC患者死亡45例,死亡组患者癌组织中KMT2D mRNA表达水平显著低于存活组、MCM6 mRNA表达水平显著高于存活组（P<0.05）。生存曲线结果显示KMT2D mRNA高表达组3年生存率显著高于KMT2D mRNA低表达组;MCM6 mRNA低表达组3年生存率显著高于MCM6 mRNA高表达组（P<0.05）。结论：MIBC癌组织中KMT2D低表达、MCM6高表达,与MIBC侵犯输尿管、淋巴结转移、TNM分期及患者预后不良有关。     

氨基酸转运载体ASCT2和LAT1在胃癌组织的表达及其临床价值

摘要 目的：研究ASC型氨基酸转运体2（ASCT2）和L型氨基酸转运体1（LAT1）在胃癌组织中的表达情况,并探讨其临床价值。方法：收集70例进展期胃癌组织以及相对应的肿瘤旁组织,采用免疫组化方法检测ASCT2和LAT1在相应组织中的表达水平,并研究其表达与患者临床病理参数和预后的相关性。结果：与癌旁组织相比,胃癌组织中ASCT2或LAT1的高表达率均有统计学差异,但其各自的表达率与癌旁组织相比无明显差异。LAT1和ASCT2在胃癌组织中的共表达率与癌旁组织相比有明显统计学差异。胃癌组织中ASCT2高表达与肿瘤体积、T分期、N分期、TNM分期和Ki-67指数显著相关;LAT1的高表达与肿瘤体积、N分期和TNM分期相关。胃癌组织中ASCT2与LAT1共表达与肿瘤体积、T分期、N分期、TNM分期和Ki-67指数显著相关。胃癌组织中ASCT2和LAT1的高表达呈正相关。胃癌组织中ASCT2高表达、LAT1高表达及ASCT2与LAT1共表达与患者不良预后有关。结论：胃癌组织中ASCT2高表达、LAT1高表达以及ASCT2与LAT1共表达提示患者预后不良,有一定临床价值。     

结直肠癌组织miR-137-3p、miR-410-3p表达水平与上皮间充质转化和预后的关系分析

摘要 目的：探讨结直肠癌（CRC）组织微小RNA-137-3p（miR-137-3p）、微小RNA-410-3p（miR-410-3p）的表达与上皮间充质转化（EMT）和预后的关系。方法：选取2017年2月至2019年2月本院收治的115例接受CRC根治术治疗的患者，采用实时荧光定量聚合酶链式反应（qRT-PCR）检测癌组织及癌旁组织中miR-137-3p、miR-410-3p表达、EMT标志物E-钙粘蛋白（E-cadherin）、波形蛋白（Vimentin）的mRNA表达并进行相关性分析，分析癌组织中miR-137-3p、miR-410-3p表达与CRC临床病理特征的关系。术后随访3年，采用Kaplan-Meier法分析miR-137-3p、miR-410-3p高表达和低表达患者的预后情况。结果：癌组织中miR-137-3p表达及E-cadherin mRNA表达水平低于癌旁组织，miR-410-3p表达及Vimentin mRNA表达水平高于癌旁组织（P＜0.05）。癌组织中miR-137-3p表达与E-cadherin mRNA表达水平、miR-410-3p表达与Vimentin mRNA表达水平分别呈正相关（P＜0.05），癌组织中miR-137-3p表达与Vimentin mRNA表达水平、miR-410-3p表达与E-cadherin mRNA表达水平分别呈负相关（P＜0.05）。miR-137-3p、miR-410-3p表达与TNM分期、肿瘤分化程度、淋巴结转移有关（P＜0.05）。Kaplan-Meier生存曲线分析显示，miR-137-3p低表达、miR-410-3p高表达患者3年累积生存率下降（P＜0.05）。结论：CRC组织中miR-137-3p表达下调、miR-410-3p表达上调，miR-137-3p、miR-410-3p表达水平与EMT密切相关，且miR-137-3p高表达、miR-410-3p低表达患者的预后更好。     

Correlation of zinc finger protein 2, a prognostic biomarker,with immune infiltrates in liver cancer

Purpose: The expression and clinical value of zinc finger protein 2 gene (ZIC2) in hepatocellular carcinoma (HCC) were analyzed by mining gene information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases.Methods: Gene chip data sets were retrieved from GEO and TCGA and screened for differentially expressed genes in HCC. Gene expression profile interaction analysis (GEPIA) and Kaplan–Meier curves were used to analyze the relationship between differentially expressed genes (DEGs) and survival and prognosis in patients with HCC. Moreover, the Genecards database was used to extract ZIC2-related proteins and to analyze the physiological process of protein enrichment. Furthermore, the relationships between ZIC2 gene and tumor cell immune invasion and that between immune cell infiltration and the 5-year survival rate were studied using the tumor immune evaluation resource (TIMER) database.Results: Datasets from GEO and TCGA revealed that ZIC2 was differentially expressed in HCC tissues and normal tissues (P<0.05). High ZIC2 expression was associated with overall survival (OS) and progress-free survival in HCC patients. Overall, 25 ZIC2 related proteins, including Gli3, PRKDC, and rnf180 were identified and protein enrichment analysis indicated these were associated with four types of cell components, six types of cell functions, and eight types of biological processes. ZIC2 was positively correlated with immune infiltration cells in patients with HCC, and higher expression of ZIC2 mRNA CD4+T cells is associated with a better 5-year survival.Conclusion: ZIC2 gene may be used as an immune response marker in liver cancer to predict the prognosis of HCC.     

CXCL2/10/12/14 are prognostic biomarkers and correlated with immune infiltration in hepatocellular carcinoma

Background: C-x-C motif chemokine ligands (CXCLs) are critical regulators of cancer immunity and angiogenesis, which affect disease progression and treatment responses. The character of each CXCL in the prognosis and immune infiltration of hepatocellular carcinoma (HCC) patients is unclear yet. Methods: Differentially expressed CXCLs between HCC and normal control were screened by Oncomine and GEPIA2. Genetic alternations of CXCLs in HCC were analyzed by cBioPortal. Clinicopathological relevance of CXCLs in HCC patients was analyzed using UALCAN. The prognostic value of CXCLs was evaluated using univariate and multivariate analyses. Correlations of CXCLs’ expression with immune infiltration, chemokines and their receptors were assessed integrating TIMER, TISIDB, and GEPIA2. The co-expressed genes of CXCLs were discovered, and functional enrichment analysis was performed for them. Results: CXCL9/10 was significantly higher expressed while CXCL2/12/14 was lower expressed in HCC than normal tissues, but they didn’t show significant clinicopathological relevance in HCC patients. High-expression of CXCL2/10/12/14 indicated favorable outcomes of HCC patients. The expression of CXCL9/10/12/14 was significantly positively correlated with not only the infiltration and biomarkers’ expression of various tumor-infiltrating immune cells but also the abundance of chemokines and their receptors. The co-expressed genes of the five CXCLs were extracellular components and regulated immune or inflammatory responses and signaling pathways of chemokine, Toll-like receptor and tumor necrosis factor might be involved. Conclusion: The present study proposed CXCL2/10/12/14 might predict outcomes of HCC patients and were extensively related with the immune microenvironment in HCC. It would be a prospective therapeutic strategy for HCC to enhance effective immunity surveillance through intervening in these CXCLs.     

RPN2与肝癌患者预后及对肝癌细胞生长的作用

目的:探讨核糖蛋白2(ribophorin II,RPN2)在肝细胞肝癌(HCC)组织中的表达和对HCC患者生存的影响,同时分析RPN2对肝癌HepG2细胞生长和克隆形成的作用。方法:应用免疫组化方法和HCC公共芯片数据,从蛋白和m RNA水平检测HCC组织中RPN2的表达,同时分析RPN2与HCC患者临床参数的关系及预后相关性;进一步利用MTS法和克隆形成实验在肝癌HepG2细胞中检测RPN2对细胞生长的作用。结果:98例肝癌组织中,RPN2阳性表达率88.78%,对应癌旁肝组织中,RPN2阳性表达率74.49%;癌组织中RPN2染色评分为5.80±3.15,癌旁肝组织RPN2染色评分为2.13±1.59,肝癌组织中RPN2表达显著上调(P0.001)。3个肝癌公共芯片数据(共522例肝癌)中RPN2的m RNA表达水平同样显著升高(均P0.001)。98例肝癌患者RPN2表达水平与肿瘤直径(P=0.004)、门脉侵袭(P=0.012)和TNM分期(P=0.009)相关;RPN2高表达的患者总体生存期(OS)和无复发生存期(RFS)较RPN2低表达的患者短(OS:P=0.027;RFS:P=0.036)。肝癌HepG2细胞转染RPN2小干扰RNA后,细胞生长能力显著受抑制。结论:RPN2在肝癌中表达显著升高,RPN2的表达与肝癌的恶性进展有关,RPN2显著促进肝癌细胞生长。     

Prognostic and immunological role of Fam20C in pan-cancer

Background: The family with sequence similarity 20-member C (Fam20C) kinase plays important roles in physiopathological process and is responsible for majority of the secreted phosphoproteome, including substrates associated with tumor cell migration. However, it remains unclear whether Fam20C plays a role in cancers. Here, we aimed to analyze the expression and prognostic value of Fam20C in pan-cancer and to gain insights into the association between Fam20C and immune infiltration.Methods: We analyzed Fam20C expression patterns and the associations between Fam20C expression levels and prognosis in pan-cancer via the ONCOMINE, TIMER (Tumor Immune Estimation Resource), PrognoScan, GEPIA (Gene Expression Profiling Interactive Analysis), and Kaplan–Meier Plotter databases. After that, GEPIA and TIMER databases were applied to investigate the relations between Fam20C expression and immune infiltration across different cancer types, especially BLCA (bladder urothelial carcinoma), LGG (brain lower grade glioma), and STAD (stomach adenocarcinoma).Results: Compared with adjacent normal tissues, Fam20C was widely expressed across many cancers. In general, Fam20C showed a detrimental role in pan-cancer, it was positively associated with poor survival of BLCA, LGG, and STAD patients. Specifically, based on TCGA (The Cancer Genome Atlas) database, a high expression level of Fam20C was associated with worse prognostic value in stages T2–T4 and stages N0–N2 in the cohort of STAD patients. Moreover, Fam20C expression had positive associations with immune infiltration, including CD4⁺ T cells, macrophages, neutrophils, and dendritic cells, and other diverse immune cells in BLCA, LGG, and STAD.Conclusion: Fam20C may serve as a promising prognostic biomarker in pan-cancer and has positive associations with immune infiltrates.     

The relationship among Girdin DNA methylation,its high expression,and immune infiltration in hepatocellular carcinoma: Clues from in silico analysis

Objective: The aim of the present study was to explore the relationship among Girdin DNA methylation, its high expression, and immune infiltration in human hepatocellular carcinoma (HCC).Materials and methods: The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and International Cancer Genome Consortium (ICGC) databases were used to compare Girdin mRNA expression between HCC tissues and normal tissues, and determine the relationship between Girdin expression and HCC prognosis. TCGA database was also used to analyze the expression of Girdin and its methylation status, as well as the relationship between Girdin DNA methylation and HCC prognosis. The Tumor IMmune Estimation Resource (TIMER) database was used to explore the correlation between Girdin expression and HCC immune infiltration.Results: Girdin expression was elevated in HCC tissues compared with that in normal tissues. The degree of methylation at cg03188526, a CpG site in the Girdin gene body, was positively correlated with Girdin mRNA expression, while high Girdin expression and cg03188526 hypermethylation were both correlated with poor HCC prognosis. Additionally, HCC tissue with high Girdin expression exhibited abundant immune infiltration, and the high Girdin expression was associated with a worse prognosis in macrophage-enriched HCC specimens.Conclusion: Our findings indicated that Girdin likely functions as an oncogene in HCC and that hypermethylation at cg03188526 in the Girdin gene body may explain the high Girdin expression levels in HCC tissue. Furthermore, we report for the first time that the adverse effects of high Girdin expression in HCC patients may be partially mediated by tumor macrophage infiltration.     

肝细胞癌患者自噬相关基因的预后作用

构建由自噬相关基因组成的预后模型,预测肝细胞癌(HCC)患者的生存预后情况,为其个性化诊疗和临床研究提供依据.利用TCGA数据库中HCC的测序信息与人类自噬数据库联合,筛选差异表达的自噬相关基因,对其进行GO富集与KEGG通路分析;通过单因素与多因素Cox分析筛选与患者生存预后明显相关的风险基因,构建预后风险评分模型;...     

ALYREF associated with immune infiltration is a prognostic biomarker in hepatocellular carcinoma

BackgroundAlthough ALYREF has been demonstrated to have a role in a number of malignancies, its role in hepatocellular carcinoma (HCC) has received little attention. Our objective was to research at the prognostic value, biological role and relevance of ALYREF to the immune system in HCC.MethodsThe expression of ALYREF and its relationship with clinical parameters of HCC patients were analyzed by liver cancer cohort (LIHC) of The Cancer Genome Atlas. The expression and prognosis were verified by immunohistochemistry experiments. Gene transfection, CCK-8, scratch healing, transwell invasion and flow cytometry were used to assess the molecular function of ALYREF in vitro. The TIMER and TISIDB online data portals were used to assess the relevance of ALYREF to immunization. Stepwise regression analysis of ALYREF-related immune genes in the LIHC training set was used to construct a prognostic risk prediction model. Also, construct a nomogram to predict patient survival. The testing set for internal verification.ResultsKnockdown of ALYREF changed the biological phenotypes of HCC cells, such as proliferation, apoptosis, and invasion. In addition, the expression of ALYREF in HCC affected the level of immune cell infiltration and correlated with the overall survival time of patients. The constructed immune prognostic model allows for a valid assessment of patients.ConclusionALYREF is increased in HCC, has an impact on cellular function and the immune system, and might be used as a prognostic marker.     

氨基酸转运载体SLC1A5在胃癌组织中的表达及其临床病理学意义

目的:研究氨基酸转运载体溶质载体家族1成员5(Solute Carrier Family 1 Member 5, SLC1A5)蛋白在胃癌组织中的表达情况,并探讨其与胃癌临床病理特征及预后的相关性。方法:收集进展期胃癌组织及对应癌旁组织90例,应用免疫组化技术检测SLC1A5在上述组织中的表达情况,并统计分析其表达与胃癌临床病理特征及预后的关系。同时通过基因数据库分析SLC1A5在胃癌组织和癌旁组织中表达情况及其对胃癌患者预后的影响。结果:与癌旁组织相比,胃癌组织中SLC1A5表达明显上调(P0.0001)。数据库研究也显示SLC1A5在胃癌组织中表达明显上调(GSE 65801,P=0.0046;GSE 63809,P0.0001;GSE 27342,P=0.0147)。胃癌组织中SLC1A5高表达与肿瘤大小(P0.05)、肿瘤浸润深度(P0.01)、淋巴结转移(P0.05)、TNM分期(P0.05)和Ki-67(P0.01)相关,而与年龄、性别、肿瘤位置及分化程度均无显著相关性(P0.05)。胃癌组织中SLC1A5表达强度与患者预后相关,表达越高,患者预后越差(总体生存率,P=0.0131;无复发生存率,P=0.0293)。数据库分析也显示SLC1A5高表达可明显缩短患者的总体生存期(GSE 14210,P=0.011;GSE 22377,P=0.0015)和无进展生存期(GSE 14210,P=0.0095;GSE 22377,P=0.0012)。结论:SLC1A5蛋白表达在胃癌组织中明显上调,且与肿瘤大小、肿瘤浸润深度、淋巴结转移及TNM分期有关。SLC1A5高表达与胃癌患者预后不良密切相关。     

Correlation analysis of RDM1 gene with immune infiltration and clinical prognosis of hepatocellular carcinoma

Purpose: Liver hepatocellular carcinoma (LIHC) is one of the most common primary malignant liver tumors worldwide. The RAD52 motif-containing protein 1 (RDM1) has been shown to play a role in mediating DNA damage repair and homologous recombination. The present study was designed to determine the expression of RDM1 and its prognostic value as well as its relationship with immune infiltration in LIHC patients.Methods: Oncomine and Tumor Immunoassay Resource were used to assess the expression of RDM1. PrognoScan and Kaplan–Meier bioinformatics database were used to analyze the impact of clinical influencing factors on prognosis. Finally, the Tumor Immune Assessment Resource (TIMER) and Gene Expression Analysis Interactive Analysis (GEPIA) databases were used to detect the correlation between the expression of RDM1 and expression of marker genes related to immune infiltration. Immunohistochemistry (IHC) method was used to detect the expression level of RDM1 in 90 cases of hepatocellular carcinoma and adjacent normal liver tissues.Results: RDM1 expression was up-regulated in most cancers. The expression of RDM1 was remarkably higher than that of the corresponding normal control genes in LIHC tissues. The increase in RDM1 messenger RNA (mRNA) expression was closely related to the decreases in overall survival (OS) and progression-free survival (PFS). Additionally, the increase in RDM1 mRNA expression was closely related to the infiltration levels of macrophages, CD8⁺ T cells and B cells and was positively correlated with a variety of immune markers in LIHC.Conclusion: The findings of the present study demonstrate that RDM1 is a potentially valuable prognostic biomarker that can help determine the progression of cancer and is associated with immune cell infiltration in LIHC.