MicroRNAs as potential biomarkers for VERO cell tumorigenicity

MicroRNA expression appears to capture the process of neoplastic development in vitro in the VERO line of African green monkey kidney (AGMK) cells (Teferedegne et al. PLoS One 2010;5(12):e14416). In that study, specific miRNA signatures were correlated with the transition, during serial tissue-culture passage, of low-density passaged 10–87 VERO cells from a non-tumorigenic phenotype at passage (p) 148 to a tumorigenic phenotype at p256. In the present study, six miRNAs (miR-376a, miR-654-3p, miR-543, miR-299-3p, miR-134 and miR-369-3p) were chosen from the identified signature miRNAs for evaluation of their use as potential biomarkers to track the progression of neoplastic development in VERO cells. Cells from the 10–87 VERO cell line at passage levels from p148 to p256 were inoculated into newborn and adult athymic nude mice. No tumors were observed in animals inoculated with cells from p148 to p186. In contrast, tumor incidences of 20% developed only in newborn mice that received 10–87 VERO cells at p194, p234 and p256. By qPCR profiling of the signature miRNAs of 10–87 VERO cells from these cell banks, we identified p194 as the level at which signature miRNAs elevated concurrently with the acquisition of tumorigenic phenotype with similar levels expressed beyond this passage. In wound-healing assays at 10-passage intervals between p150 to p250, the cells displayed a progressive increase in migration from p165 to p186; beginning at p194 and higher passages thereafter, the cells exhibited the highest rates of migration. By qPCR analysis, the same signature miRNAs were overexpressed with concomitant acquisition of the tumorigenic phenotype in another lineage of 10–87 VERO cells passaged independently at high density. Correlation between the passages at which the cells expressed a tumorigenic phenotype and the passages representing peaks in expression levels of signature miRNAs indicates that these miRNAs are potential biomarkers for the expression of the VERO cell tumorigenic phenotype.     

血浆miRNA表达与儿童急性淋巴细胞白血病风险的关联研究

目的 探讨miRNA在儿童急性淋巴细胞白血病（cALL）病例血浆中的表达分布特征,分析其与cALL发病风险之间的关系,并判断miRNA作为cALL诊断标记物的可行性。方法 采用病例对照方法,收集2015年1月至2016年11月在深圳市儿童医院确诊初发cALL和骨折病例作为对照各111例,按性别相同和年龄（±1岁）进行1：1匹配,并从中选择4对cALL病例和对照进行LNA^TM miRNA表达谱芯片检测。采用实时定量PCR验证miRNA表达水平,利用条件logistic回归分析miRNA与cALL发病风险之间的关系,以受试者工作特征曲线（ROC）和重新分类方法分析miRNA作为cALL生物标志物的可行性。结果 芯片筛选出204个差异表达的miRNA。根据入选条件,纳入let-7f-5p、miR-5100、miR-25-3p和miR-3654进行实时定量PCR。病例组let-7f-5p、miR-5100和miR-25-3p的表达水平低于对照组,差异有统计学意义（P<0.01）。在调整混杂因素后,这3个miRNA仍然与cALL的发生存在关联[OR值和95%CI分别为0.84（0.76~0.92）、0.81（0.73~0.90）、0.81（0.74~0.89）]。ROC和重新分类法结果显示与传统危险因素模型相比,加入1个或≥ 2个miRNA均增加曲线下面积（P<0.05）,且模型诊断均有增加价值作用（P<0.01）。结论 let-7f-5p、miR-5100、miR-25-3p的表达水平与cALL的发生关联,可作为cALL的生物标志物。     

Sex-Biased miRNA Expression in Atlantic Halibut (Hippoglossus hippoglossus) Brain and Gonads

The role of miRNA in fish sexual development is not elucidated yet. We profiled miRNAs in gonads and brains of Atlantic halibut using SOLiD sequencing technology. We found tissue- and sexually dimorphic expression of several miRNAs, including miR-29a, miR-34, miR-143, miR-145, miR-202-3p, miR-451, and miR-2188. miR-9 and miR-202 were abundant in brain and gonads, respectively. In the next step, we selected some miRNAs showing differential expression patterns between sexes and performed RT-qPCR on 3 age groups: juveniles, 3-year-, and 5-year-olds. In brains, miR-451 was significantly down-regulated in juveniles compared to adults. let-7a, miR-143, and miR-202-3p were up-regulated in gonads of mature males compared to immature females at the same age. We investigated the effect of suppressing aromatase cytochrome P450 enzyme on miRNA expression at the onset of sex differentiation through masculinization with Fadrozole or 17-α-methyltestosterone. We found significant differences in miRNA expression between masculinized individuals and untreated controls. miR-202-3p was significantly down-regulated in female juveniles compared to male juveniles. The expression levels of let-7a and miR-451 were restored after termination of the masculinization treatment. Our data give a first insight into miRNA involvement in sexual development in teleosts.     

Circulating miR-29c,miR-30c,miR-193a-5p and miR-885-5p: Novel potential biomarkers for HTLV-1 infection diagnosis

Human T-cell leukemia virus type 1 (HTLV-1) is an oncoretrovirus that infects 5–10 million people worldwide. Currently, different methods are used to test HTLV-1 infection. However, a biomarker that could enable an early and accurate diagnosis of HTLV-1 infection is still lacking. Here, we compared the serum miRNA expression profile in HTLV-1 infected patients versus healthy individuals to identify a potential biomarker for diagnosis of HTLV-1 infection.TaqMan miRNA microarray (TLDA) was carried out to compare the miRNA expression profile in infected versus healthy individuals. Quantitative real-time RT-PCR (qRT-PCR) was applied to validate TLDA results. Receiver-operator characteristic (ROC) curve analysis was performed to determine the diagnostic accuracy of the most highly and significantly identified deregulated miRNA(s) as potential biomarker(s). We identified deregulated expression for ten miRNAs with miR-127, miR-136, miR-142-3p, miR-221, and miR-423-5p being down-regulated whilst let-7b, miR-29c, miR-30c, miR-193a-5p, and miR-885-5p being up-regulated in infected individuals. ROC curve analyses showed an AUC (Areas Under the ROC Curve) of 0.875 (95% CI: 0.7819–0.9581; P = .0021), 0.861 (95% CI: 0.7596–0.9754; P = .003), 0.856 (95% CI: 0.689–0.895; P = .011), and 0.849 (95% CI: 0.678–0.855; P = .017) for miR-29c, miR-30c, miR-193a-5p, and miR-885-5p respectively. Combined ROC analyses using these 4 miRNAs showed a greater AUC of 0.907 (95% CI: 0.809–1; P = .000001) indicating a robust diagnostic value of these 4 miRNAs. Our findings highlight serum miR-29c, miR-30c, miR-193a-5p and miR-885-5p as novel potential biomarkers important for HTLV-1 diagnosis.     

Circulating microRNAs as potential biomarkers of HBV infection persistence

ObjectivesTo investigate different microRNA (miRNA) expression profile in patients of hepatitis B virus (HBV) infection compared with virus spontaneous clearance ones, and try to find new biomarker for diagnosis and treatment assessment.MethodsmiRNA expression profiling was analyzed in patients with HBV infection and patients with virus spontaneous clearance by Affymetrix Gene Chip miRNA 4.0 Arrays. The differently expressed miRNAs, as verified by RT-PCR, were analyzed and compared with each other in the two groups of patients.ResultsSignificant difference was found in the expression of miR-29b, miR-34, miR-4485, miR-3180, miR-125, miR-330-3p, miR-1468 in spontaneous clearance group and CHB group. miR-29b, miR-34, miR-4485 was significantly increased in CHB group, while miR-125, miR-330-3p, miR-1468, miR-3180 was significantly decreased. Correlation analysis indicate only miR-29b was positive correlation with HBsAg.ConclusionsThese results indicated above miRNAs may be associated with HBV infection persistence, and provided us new ideas for finding potential biomarkers.     

MicroRNA 在多囊卵巢综合征中的表达及作用

非编码微小RNAs（microRNAs,miRNAs）主要在转录后水平上调控基因表达,异常miRNA表达与胰岛素抵抗、糖尿病、炎症及各种癌症形成有关。多囊卵巢综合征（polycystic ovary syndrome,PCOS）患者血清及卵泡液中miRNAs表达谱存在差异,其异常的miRNAs表达能够通过影响基因转录后水平,参与PCOS的发生发展。综述miR-93、miR-222、miR-92a/b、miR-224、miR-320、miR-9、miR-483-5p、miR-513a-3p、miR-24、miR-133b、miR-26b和miR-378在PCOS患者的胰岛素抵抗、性激素合成和分泌、颗粒细胞增生、卵泡发育异常及排卵障碍中的作用,探讨miRNA在PCOS发病机制中的作用。     

肺癌诊断相关miRNA标志物的筛选和验证

目的 获得肺癌组织和正常肺部组织中差异表达的miRNA用于肺癌的早期诊断.方法 首先运用miRNA芯片比较5对来自临床的正常肺部组织和肺癌组织,筛选差异性表达的miRNA,然后用荧光实时定量PCR进行鉴定.最后用ROC曲线分析评价特定miRNA标志物区分肺癌组织与正常肺部组织的能力.结果 miR-10b-5p和miR-199a-5p在肺癌组织中的相对表达量(2.76±0.71;2.05±0.38)显著高于肺部正常组织中的相对表达量(1.00±0.17;0.96±0.18),差异有统计学意义(t=2.40、2.56,P＜0.05).ROC曲线评价miR-10b-5p和miR-199a-5p区分肺癌组织和肺部正常组织的能力,曲线下面积(AUC)分别为0.731和0.672.两个miRNA联合区分肺癌组织和肺部正常组织的AUC为0.773,灵敏度为57.9％,特异性为94.7％.结论 miR-10b-5p和miR-199a-5p联合可作为候选肿瘤标志物组合用于早期肺癌诊断.     

Astaxanthin Attenuates the Changes in the Expression of MicroRNAs Involved in the Activation of Hepatic Stellate Cells

We previously demonstrated that astaxanthin (ASTX), a xanthophyll carotenoid, has an antifibrogenic effect in hepatic stellate cells (HSC), primarily responsible for the accumulation of extracellular matrix protein during the development of liver fibrosis. Studies have shown that microRNAs (miRNAs) are involved in HSC activation. Therefore, we analyzed the expression of 84 miRNAs using miRNA arrays in primary mouse quiescent HSC (qHSC) and activated HSC (aHSC) treated with/without ASTX during their activation. Compared with qHSC, the expression of 14 miRNAs and 23 miRNAs was increased and decreased by more than 2-fold, respectively, in aHSC. Among the 14 miRNAs increased in aHSC, the expression of miR-192-5p, miR-382-5p, and miR-874-3p was reduced by ASTX. In addition, ASTX increased the expression of miR-19a-3p, miR-19b-3p, and miR-101a-3p among 23 miRNAs decreased in aHSC. Moreover, we confirmed miR-382-5p expression was ~15-fold higher in aHSC than qHSC, and ASTX markedly inhibited the induction measured by quantitative real-time PCR. We identified that the expression of Baz1a and Zfp462 from the predicted miR-382-5p target genes was significantly reduced in aHSC while increased by ASTX treatment similar to the levels in qHSC. The roles of Baz1a and Zfp462 in HSC activation and the antifibrogenic effect of ASTX need to be further investigated.     

Plasma microRNA Expression and Micronuclei Frequency in Workers Exposed to Polycyclic Aromatic Hydrocarbons

Background: Ubiquitous polycyclic aromatic hydrocarbons (PAHs) have been shown to alter gene expression patterns and elevate micronuclei (MN) frequency, but the underlying mechanisms are largely unknown. MicroRNAs (miRNAs) are key gene regulators that may be influenced by PAH exposures and mediate their effects on MN frequency.Objectives: We sought to identify PAH-associated miRNAs and evaluate their associations with MN frequency.Methods: We performed a two-stage study in healthy male coke oven workers to identify miRNAs associated with PAH exposures quantified using urinary monohydroxy-PAHs and plasma benzo[a]pyrene-r-7,t-8,c-10-tetrahydrotetrol-albumin (BPDE–Alb) adducts. In the discovery stage, we used Solexa sequencing to test differences in miRNA expression profiles between pooled plasma samples from 20 exposed workers and 20 controls. We then validated associations with eight selected miRNAs in 365 workers. We further evaluated associations between the PAH-associated miRNAs and MN frequency.Results: In the discovery stage, miRNA expression profiles differed between the exposed and control groups, with 68 miRNAs significantly down-regulated [fold change (FC) ≤ –5] and 3 miRNAs mildly up-regulated (+2 ≤ FC < +5) in the exposed group. In the validation analysis, urinary 4-hydroxyphenanthrene and/or plasma BPDE–Alb adducts were associated with lower miR-24-3p, miR-27a-3p, miR-142-5p, and miR-28-5p expression (p < 0.030). Urinary 1-hydroxynaphthalene, 2-hydroxynaphthalene, 2-hydroxyphenanthrene, and the sum of monohydroxy-PAHs were associated with higher miR-150-5p expression (p < 0.030). These miRNAs were associated with higher MN frequency (p < 0.005), with stronger associations in drinkers (p_interaction < 0.015).Conclusions: Associations of PAH exposures with miRNA expression, and of miRNA expression with MN frequency, suggest potential mechanisms of adverse effects of PAHs that are worthy of further investigation.Citation: Deng Q, Huang S, Zhang X, Zhang W, Feng J, Wang T, Hu D, Guan L, Li J, Dai X, Deng H, Zhang X, Wu T. 2014. Plasma microRNA expression and micronuclei frequency in workers exposed to polycyclic aromatic hydrocarbons. Environ Health Perspect 122:719–725; http://dx.doi.org/10.1289/ehp.1307080     

Genomic changes detected after serial passages in cell culture of virulent human G1P[8] rotaviruses

Serial passages of a virulent mouse rotavirus in cell cultures caused a loss of virulence in mice. To gain insight into the genomic mutations in human rotavirus during cell culture and its attenuation in humans, we serially passaged three wild type human G1P[8] rotavirus strains (Wa, DC3695, DC5685) derived from diarrheal stool samples up to 60 times in two different cell cultures (human colon adenocarcinoma cell line: HT29, and primary African green monkey kidney cells: primary AGMK). We sequenced the whole genomes of 60 times-passaged strains and compared them with those of the original viruses. Most substitutions were detected in VP4, followed by substitutions in VP7 and NSP4 genes. Substitution at amino acid 385 in the putative VP4 fusion domain and substitution T45M in NSP4 genes were detected in all AGMK-passaged strains, respectively. These genomic changes are likely to correlate with a loss of rotavirus virulence in humans.     

MicroRNAs as Potential Signatures of Environmental Exposure or Effect: A Systematic Review

Background: The exposome encompasses all life-course environmental exposures from the prenatal period onward that influence health. MicroRNAs (miRNAs) are interesting entities within this concept as markers and causation of disease. MicroRNAs are short oligonucleotide sequences that can interact with several mRNA targets.Objectives: We reviewed the current state of the field on the potential of using miRNAs as biomarkers for environmental exposure. We investigated miRNA signatures in response to all types of environmental exposure to which a human can be exposed, including cigarette smoke, air pollution, nanoparticles, and diverse chemicals; and we examined the health conditions for which the identified miRNAs have been reported (i.e., cardiovascular disease, cancer, and diabetes).Methods: We searched the PubMed and ScienceDirect databases to identify relevant studies.Results: For all exposures incorporated in this review, 27 miRNAs were differentially expressed in at least two independent studies. miRNAs that had expression alterations associated with smoking observed in multiple studies are miR-21, miR-34b, miR-125b, miR-146a, miR-223, and miR-340; and those miRNAs that were observed in multiple air pollution studies are miR-9, miR-10b, miR-21, miR-128, miR-143, miR-155, miR-222, miR-223, and miR-338. We found little overlap among in vitro, in vivo, and human studies between miRNAs and exposure. Here, we report on disease associations for those miRNAs identified in multiple studies on exposure.Conclusions: miRNA changes may be sensitive indicators of the effects of acute and chronic environmental exposure. Therefore, miRNAs are valuable novel biomarkers for exposure. Further studies should elucidate the role of the mediation effect of miRNA between exposures and effect through all stages of life to provide a more accurate assessment of the consequences of miRNA changes.Citation: Vrijens K, Bollati V, Nawrot TS. 2015. MicroRNAs as potential signatures of environmental exposure or effect: a systematic review. Environ Health Perspect 123:399–411; http://dx.doi.org/10.1289/ehp.1408459     

Serum miRNA profiling identifies miR-150/30a as potential biomarker for workers with damaged nerve fibers from carbon disulfide

As crucial small regulatory molecules, serum microRNAs (miRNAs) have been widely identified as potential noninvasive biomarkers. To survey and identify serum miRNAs associated with workers who had experienced injury to their nerve system from carbon disulfide (CS₂), we profiled abnormally expressed miRNAs using the microarray technique and further performed qRT-PCR validation in case and control samples (n=20). Microarray profiling in pooled RNA samples showed that many miRNAs in workers exposed to CS₂ were aberrantly expressed. Based on control samples exposed to CS₂, a great amount of abnormal miRNAs, including some miRNA gene clusters and families, were obtained from microarray datasets. Most of deregulated miRNAs were up-regulated, and almost all miRNAs showed consistent expression patterns between workers with different numbers of damaged nerve fibers. Functional enrichment analysis suggested that these abnormal miRNAs showed versatile roles by contributing to multiple biological processes. Some aberrantly expressed miRNAs were characterized as miRNA gene clusters or families, and they always showed consistent expression patterns. miR-150 and miR-30a were selected to be further validated by qRT-PCR as up-regulated species, and they could discern case samples from control samples. miR-150 and miR-30a may be potential noninvasive biomarkers for a damaged nervous system.     

MicroRNAs in hepatocarcinogenesis

The details of molecular alterations occurring during hepatocarcinogenesis have not been revealed yet. Nevertheless, it is known that microRNAs (miRNA), these short RNA molecules regulating gene expression mainly in a negative way, are also involved in this process. Altered miRNA expression levels are present in liver diseases when compared with normal liver tissue, and the observed alterations depend mainly on which is more advantegous for the disease: activation or inhibition of the genes (e.g. oncogenes or tumor suppressor genes) regulated by the altered miRNAs. The miRNA expression pattern described in hepatocellular carcinoma seems to differ the most from that found in the normal liver; however, remarkable alterations at miRNA levels have been published in early stages of hepatic tumor progression such as fibrosis and chronic hepatitis. For example, the expression of miR-21, miR-221, miR-222 and miR-199a showing characteristic alterations in hepatocellular carcinoma also displayed deregulated expressions in these two early stages. The liver characteristic miRNA, miR-122, usually exhibits a decreased expression level upon liver injury as well as miR-122 expression tends to decrease as hepatic carcinogenesis progresses. Besides, miR-122 enhances the replication of hepatitis C virus and the initial low or high level of miR-122 seems to influence the efficiency of interferon therapy. Recently, statistically significant differences have been detected in the expression of several miRNAs being present in the serum of patients with chronic hepatitis, chirrhosis and hepatocellular carcinoma when compared with normal controls. It suggests that serum miRNAs could be potential biomarkers. In this article, the major and recent alterations of microRNA expression patterns in stages of hepatocarcinogenesis such as fibrosis, viral infections (hepatitis), cirrhosis and hepatocellular carcinoma are summarized.     

Circulating miRNAs: Potential diagnostic role for coronavirus disease 2019 (COVID-19)

Nowadays, the coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a major global health problem. Intensive efforts are being employed to better understand this pathology and develop strategies enabling its early diagnosis and efficient treatment. In this study, we compared the signature of circulating miRNAs in plasma of COVID-19 patients versus healthy donors. MiRCURY LNA miRNA miRNome qPCR Panels were performed for miRNA signature characterization. Individual quantitative real-time PCR (qRT-PCR) was carried out to validate miRNome qPCR results. Receiver-operator characteristic (ROC) curve analysis was applied to assess the diagnostic accuracy of the most significantly deregulated miRNA(s) as potential diagnostic biomarker(s). Eight miRNAs were identified to be differentially expressed with miR-17-5p and miR-142-5p being down-regulated whilst miR-15a-5p, miR-19a-3p, miR-19b-3p, miR-23a-3p, miR-92a-3p and miR-320a being up-regulated in SARS-CoV-2-infected patients. ROC curve analyses revealed an AUC (Areas Under the ROC Curve) of 0.815 (P = 0.031), 0.875 (P = 0.012), and 0.850 (P = 0.025) for miR-19a-3p, miR-19b-3p, and miR-92a-3p, respectively. Combined ROC analyses using these 3 miRNAs showed a greater AUC of 0.917 (P = 0.0001) indicating a robust diagnostic value of these 3 miRNAs. These results suggest that plasma miR-19a-3p, miR-19b-3p, and miR-92a-3p expression levels could serve as potential diagnostic biomarker and/or a putative therapeutic target during SARS-CoV-2-infection.     

二羟环氧苯并芘恶性转化细胞的microRNA表达谱

目的 检测二羟环氧苯并芘(BPDE)恶性转化细胞的microRNA(miRNA)表达谱,寻找恶性转化细胞与对照细胞差异表达的miRNA.方法 以溶剂二甲亚砜助溶的终浓度为2.0 μmol/L的BPDE培养液培养人支气管上皮细胞株16HBE,获得BPDE恶性转化的细胞模型为实验组,同时,以含二甲亚砜的培养液培养正常16HBE作为对照组.通过微阵列技术检测实验组与对照组327个人类miRNA,并选择差异表达明显的miR-10a和miR-320用反转录荧光定量PCR方法对微阵列结果加以验证.结果 获得2组细胞327个miRNA表达谱,发现差异表达miRNA 55个,其中46个表达上调,9个表达下调,并得到反转录荧光定量PCR的验证.结论 获得BPDE恶性转化细胞与正常16HBE细胞差异表达的miRNA,为进一步寻找BPDE恶性转化细胞特征性miRNA提供了研究基础.     

早期妊娠丢失蜕膜组织中与血管重塑相关的miRNAs表达谱分析

目的：通过对子宫内膜蜕膜化中与血管重塑相关的miRNAs表达谱的芯片筛查及相关靶基因预测，为早期妊娠丢失的发病机制研究奠定基础。方法：利用miRNA array芯片检测早期妊娠丢失患者蜕膜组织中的差异表达miRNAs，确定与血管重塑相关的miRNAs表达谱，进而应用miRWalk2.0数据库通过生物信息学方法预测差异表达miRNAs的相关靶基因，最后应用DAVID数据库对相关靶基因进行功能富集分析（GO-analysis）及靶基因信号转导通路富集分析（KEGG Pathway analysis）。结果：早期妊娠丢失患者蜕膜组织中差异表达的miRNAs共70条，上调表达miRNAs 32条，下调表达miRNAs 38条。其中差异倍数最高（≥2.0）的2个上调miRNA为miR-125a-5p和miR-29c-3p，预测相关靶基因为血管内皮生长因子A（VEGFA）。靶基因集合功能富集于正调控RNA代谢过程、血管发育、脉管系统发育、正调控内皮细胞增殖、缺氧反应、血管生成等分子过程；KEGG通路分析涉及哺乳动物雷帕霉素靶蛋白（mTOR）信号通路、丝裂原活化蛋白激酶（MAPK）等信号通路。结论：miR-125a-5p和miR-29c-3p在早期妊娠丢失患者蜕膜组织中上调表达，可能通过对靶基因VEGFA的调控，影响子宫内膜蜕膜化血管重塑的过程，参与流产发生。     

基于TCGA数据库构建肺腺癌预后相关的微小RNAs风险模型

目的寻找肺腺癌(lung adenocarcinoma,LUAD)特异性的预后相关微小RNAs(microRNAs, miRNAs),为LUAD患者预后预测及个性化治疗方案制定提供依据。 方法下载TCGA数据库中522例LUAD患者组织标本的miRNA-Seq数据和临床病理及生存时间数据,用R语言对LUAD与癌旁组织中差异miRNAs进行分析。采用LASSO & COX回归模型在训练集(245例LUAD)中进行LUAD预后相关miRNAs筛选,并构建基于7个miRNAs表达谱的线性风险模型。根据风险值的高低,以中位风险值为界将患者分为高、低风险组,并分别在测试集(245例LUAD)和总体标本(490例LUAD)中对风险模型预测患者预后的有效性进行验证。采用COX回归分析miRNAs风险模型是否是独立的预后因子。 结果LUAD组织与癌旁组织中共有72个差异表达的miRNAs(上调45个、下调27个)。从训练集中确定miR-101-3p、miR-148a-3p、miR-192-5p、miR-193b-3p、miR-505-3p、miR-584-5p和miR-99a-5p 7个与总生存期相关的miRNAs构建预后风险模型。在训练集、测试集及总体标本中,高风险组患者与低风险组患者相比,总体生存时间均显著降低(P均<0.05)。经多因素COX回归分析,风险模型在训练集、测试集及总体样本中均是一个独立的预后因子(训练集HR=1.97,P=0.02;测试集HR=1.927,P=0.009;总体HR=1.909,P=0.001)。 结论研究确定了7个与LUAD患者预后相关的miRNAs,基于7个miRNAs构建的风险模型是1个独立的预后因子。     

Comparative sensitivity of the BGM cell line for isolation of enteric viruses.

The BGM line of African green monkey kidney cells was less sensitive than primary rhesus monkey kidney cells or human fetal diploid kidney cells for isolation of certain echoviruses and adenoviruses from fecal specimens.