miRNA-449a在肺癌组织中的表达及其检测意义

目的探讨miRNA-449a在肺癌组织中的表达及其临床应用价值。方法收集右江族医学院附属医院2011年1月1日~2013年6月30日收治的58例肺癌患者为研究对象,采用反转录荧光定量聚合酶链式反应(RT-PCR)检测miRNA-449a在肺癌组织和癌旁正常组织中的表达量,分析miRNA-449a与临床病理特征的关系,并采用荧光电子显微镜观察miRNA-449a模拟物对体外培养肺癌细胞株95D细胞凋亡的影响。结果鳞癌组和腺癌组miRNA-449a平均表达量均明显低于癌旁正常对照组(LSD-t=6.712,P=0.000;LSD-t=4.572,P=0.000),其相对表达量与瘤体大小(u=78.412,P=0.012)有关,与患者年龄(u=920.000,P=0.615)、性别(u=800.000,P=0.215)、病理类型(χ2=4.221,P=0.155)和临床分期(u=754.000,P=0.009)无关。与阴性对照组比较,miRNA-449a模拟物可明显促进肺癌细胞的凋亡,且呈剂量依赖性。结论 miRNA-449a在肺癌组织中呈低表达,可诱导肺癌细胞凋亡,发挥抑癌基因的作用,可能成为肺癌早期诊断与治疗的新分子靶标。     

甲状腺肿瘤组织中VEGF、p73蛋白表达情况及相互关系研究

目的 探析甲状腺肿瘤组织中血管内皮生长因子(VEGF)、肿瘤抑制因子(p73)的表达及其相关性.方法 选取某院2013年1月至2014年1月收治的60例甲状腺癌和60例甲状腺腺瘤患者作为观察对象,并将同期60例健康人群作为对照,采用免疫组化(SP)法检测组织中VEGF和p73的表达,并采用Pearson相关分析研究组织中VEGF和p73的相关性.结果 甲状腺癌组组织中VEGF阳性表达率86.7％(52/60)显著高于甲状腺腺瘤组71.7％(43/60),高于正常对照组0％,差异均有统计学意义(P＜0.05);甲状腺癌组组织中p73阳性表达率93.3％(56/60)显著高于甲状腺腺瘤组80.0％(48/60),高于正常对照组0％,差异均有统计学意义(P＜0.05).甲状腺组织中VEGF和p73呈正相关,在甲状腺癌组织中相关系数r=0.723,P＜0.05,在甲状腺腺瘤组织中相关系数r=0.542,P＜0.05.结论 甲状腺肿瘤患者组织中VEGF和p73蛋白表达均显著升高,且二者呈正相关.     

Preliminary evaluation of [18F]AlF-NOTA-MAL-Cys39-exendin-4 in insulinoma with PET

Background: High expression of glucagon-like peptide-1 receptor (GLP-1R) in insulinoma supplies a potential drug target for tumor imaging. Exendin-4 can specifically bind to GLP-1R as an agonist and its analogs are extensively used in receptor imaging studies.

Purpose: A new GLP-1R imaging agent, [¹⁸F]AlF-NOTA-MAL-Cys³⁹-exendin-4, was designed and prepared for insulinoma imaging.

Methods: Cys³⁹-exendin-4 was conjugated with NOTA-MAL, then the compound was radiolabeled with [¹⁸F]AlF complex to obtained [¹⁸F]AlF-NOTA-MAL-Cys³⁹-exendin-4. The tumor-targeting characters of the tracer were evaluated in INS-1 cells and BALB/c nude mice models.

Results: [¹⁸F]AlF-NOTA-MAL-Cys³⁹-exendin-4 can be efficiently produced with a yield of 17.5?±?3.2% (non-decay corrected) and radiochemical purity of >95%. The IC₅₀ value of displacement [¹⁸F]AlF-NOTA-MAL-Cys³⁹-exendin-4 with Cys³⁹-exendin-4 was 13.52?±?1.36?nM. PET images showed excellent tumor visualization with high uptake (9.15?±?1.6%ID/g at 30?min and 7.74?±?0.87%ID/g at 60?min). The tumor to muscle, pancreas and liver ratios were 63.25, 3.85 and 7.29 at 60?min after injection. GLP-1R binding specificity was demonstrated by co-injection with an excess of unlabeled Cys³⁹-exendin-4 and the tumor uptake was found to be reduced significantly.

Conclusion: [¹⁸F]AlF-NOTA-MAL-Cys³⁹-exendin-4 shows favorable characteristics for insulinoma imaging and may be translated to clinical studies.     

m6A regulators are associated with osteosarcoma metastasis and have prognostic significance: A study based on public databases

Background:Osteosarcoma represents the most common malignant bone tumor with high metastatic potential and inferior prognosis. RNA methylation (N6-methyladenosine [m6A]) is a prevalent RNA modification that epigenetically influences numerous biological processes including tumorigenesis. This study aims to determine that m6A regulators are significant biomarkers for osteosarcoma, and establish a prognostic model to predict the survival of patients.Methods:In this study, we comprehensively analyzed the underlying associations between m6A regulators’ mRNA expressions and metastasis as well as prognosis of osteosarcoma patients in the Cancer Genome Atlas. Multivariate Cox-regression analysis was used to screen regulators that were significantly associated with overall survival of osteosarcoma patients. Least absolute shrinkage and selection operator (LASSO) Cox-regression analysis was used for constructing m6A regulator-based osteosarcoma prognostic signature.Results:Some of the regulators exhibited aberrant mRNA levels between osteosarcoma samples with and without metastasis. Multivariate Cox-regression analysis identified several regulators with potential prognostic significance. A risk score formula consisted of methyltransferase-like 3, YTH domains of Homo sapiens, and fat mass and obesity-associated protein was obtained through which patients could be prognostically stratified independently of potential confounding factors. The signature was also significantly associated with the metastatic potential of osteosarcoma. All the analyses could be well reproduced in another independent osteosarcoma cohort from the Gene Expression Omnibus.Conclusions:In conclusion, this study first revealed potential roles of m6A regulators in osteosarcoma metastasis and prognosis, which should be helpful for its clinical decision-making.     

Urinary Nucleic Acid TSPAN13-to-S100A9 Ratio as a Diagnostic Marker in Prostate Cancer

The potential use of urinary nucleic acids as diagnostic markers in prostate cancer (PCa) was evaluated. Ninety-five urine samples and 234 prostate tissue samples from patients with PCa and benign prostatic hyperplasia (BPH) were analyzed. Micro-array analysis was used to identify candidate genes, which were verified by the two-gene expression ratio and validated in tissue mRNA and urinary nucleic acid cohorts. Real-time quantitative polymerase chain reaction (qPCR) was used to measure urinary nucleic acid levels and tissue mRNA expression. The TSPAN13-to-S100A9 ratio was selected to determine the diagnostic value of urinary nucleic acids in PCa (P = 0.037) and shown to be significantly higher in PCa than in BPH in the mRNA and nucleic acid cohort analyses (P < 0.001 and P = 0.013, respectively). Receiver operating characteristic (ROC) analysis showed that the area under the ROC curve was 0.898 and 0.676 in tissue mRNA cohort and urinary nucleic acid cohort, respectively. The TSPAN13-to-S100A9 ratio showed a strong potential as a diagnostic marker for PCa. The present results suggest that the analysis of urine supernatant can be used as a simple diagnostic method for PCa that can be adapted to the clinical setting in the future.     

孕妇血清微小RNA-423对胎儿神经管缺陷产前诊断的意义

目的 母亲血清中微小RNA(microRNA,miRNA)的发现为无创性产前诊断开辟了新途径.但是对神经管缺陷胎儿母亲血清中妊娠相关的miRNA的研究甚少.该文旨在研究微小RNA-423(mi-croRNA-423,miR-423)在神经管缺陷胎儿孕妇血清中的异常表达及其作为潜在诊断标志物的临床价值.方法 33例产前超声检查确诊为胎儿神经管缺陷的患儿为研究对象,其中脊柱裂22例,无脑儿11例;33例胎儿健康孕妇为对照组.所有孕妇均于清晨空腹抽外周静脉血5ml离心后取血清,提取血清总RNA,用Real-time RT-PCR方法测定miR-423表达水平.并用ROC曲线分析用miR-423诊断胎儿神经管缺陷的价值.结果 神经管缺陷胎儿孕妇血清中miR-423含量(0.96±0.14)明显低于健康胎儿孕妇对照组(2.28±0.43),P＜0.05.ROC分析miR-423曲线下面积为0.711(95％ CI:0.566～0.856)(P＜0.05).另外,对不同类型的神经管缺陷孕妇血清中的miR-423表达水平分析发现,只有在无脑儿中表达降低(0.58±0.08)差异有统计学意义.结论 孕妇血清中miR-423可作为胎儿神经管缺陷的无创性产前诊断标志物,具有潜在的临床价值,可能预示胎儿神经管缺陷严重程度.     

MiR-122 and other microRNAs as potential circulating biomarkers of drug-induced liver injury

Introduction: Drug-induced liver injury (DILI) is a severe adverse drug reaction which is of major concern to patients, clinicians and the pharmaceutical industry. Accurate and rapid detection of DILI is important for patient stratification and treatment in the clinic and benefits preclinical drug design and risk assessment. MicroRNAs (miRNAs) offer a potential new and improved class of circulating biomarkers of DILI over the current gold standard biomarkers.

Areas covered: This review highlights the shortcomings of the currently used panel of biomarkers and how miRNAs, primarily miR-122, show an improved level of specificity and sensitivity in the prediction of DILI. Furthermore, the use of miRNAs as potential markers of progression of DILI and specific zonated damage within the liver is discussed.

Expert commentary: MiRNAs offer more sensitive and specific markers over the current biomarkers for DILI. Combinations of different miRNAs may be able to relay the location of DILI and the progression of disease. More studies using different hepatotoxins apart from acetaminophen will ultimately strengthen the case for the clinical introduction of miRNAs as biomarkers of DILI.