Gene Expression Regulation, Neoplastic

基因表达调控, 肿瘤
  • 文章类型: Journal Article
    硒在食管癌(EC)发育过程中的作用需要进一步研究。通过生物信息学分析探讨硒相关因子与EC的关系,我们进行了一项病例对照研究以验证结果.利用GEPIA和TCGA数据库,我们描述了谷胱甘肽过氧化物酶3(GPx3)在EC和正常组织中的差异表达,鉴定的差异表达基因(DEGs),和执行的可视化分析。此外,来自淮安地区的食管鳞癌(ESCC)病例和健康对照的100对食道癌前病变(EPLs)的饮食和血浆样本,江苏,被筛选。日粮硒的水平,等离子体硒,使用电感耦合等离子体质谱(ICP-MS)或ELISA试剂盒分析相关酶。结果显示与正常组织相比,肿瘤组织中的GPx3表达较低。进一步分析发现DEGs主要参与脂肪的消化吸收途径,核心蛋白脂肪酸结合蛋白1(FABP1)表达明显上调,与GPx3表达呈负相关。我们的病例对照研究发现,硒本身与EPL风险无关。然而,GPx3浓度降低和FABP1升高均与EPL风险呈正相关(趋势p分别为0.035和0.046).GPx3和FABP1的不同表达反映了硒在EPL阶段预防ESCC的潜力。GPx3可能通过FABP1影响心肌梗死,有待进一步研究。
    The role of selenium in the developmental process of esophageal cancer (EC) requires further investigation. To explore the relationship between selenium-related factors and EC through bioinformatic analysis, a case-control study was conducted to verify the results. Utilizing the GEPIA and TCGA databases, we delineated the differential expression of glutathione peroxidase 3 (GPx3) in EC and normal tissues, identified differentially expressed genes (DEGs), and a performed visualization analysis. Additionally, 100 pairs of dietary and plasma samples from esophageal precancerous lesions (EPLs) of esophageal squamous cancer (ESCC) cases and healthy controls from Huai\'an district, Jiangsu, were screened. The levels of dietary selenium, plasma selenium, and related enzymes were analyzed using inductively coupled plasma mass spectrometry (ICP-MS) or ELISA kits. The results showed lower GPx3 expression in tumor tissues compared to normal tissues. Further analysis revealed that DEGs were mainly involved in the fat digestion and absorption pathway, and the core protein fatty acid binding protein 1 (FABP1) was significantly upregulated and negatively correlated with GPx3 expression. Our case-control study found that selenium itself was not associated with EPLs risk. However, both the decreased concentration of GPx3 and the increase in FABP1 were positively correlated with the EPLs risk (p for trend = 0.035 and 0.046, respectively). The different expressions of GPx3 and FABP1 reflect the potential of selenium for preventing ESCC at the EPLs stage. GPx3 may affect myocardial infarction through FABP1, which remains to be further studied.
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  • 文章类型: Journal Article
    目的:本研究旨在探讨CD276与肾透明细胞癌(ccRCC)的关系,并评估CD276在ccRCC中的诊断价值。
    方法:使用TCGA和GEO数据库获得的数据对ccRCC和癌旁组织中CD276的表达水平进行比较和回顾性分析。对其临床资料进行前瞻性分析。免疫组织化学和RT-PCR分析用于在mRNA和蛋白质水平上分析CD276的表达。这些分析比较了从70例ccRCC患者获得的ccRCC组织和癌旁组织之间的表达。接下来,采用ELISA方法对70例ccRCC患者和72例健康人的外周血标本进行分析,促进ccRCC患者与正常对照的分化。最后,我们利用Kaplan-Meier方法生成ROC曲线,以评估CD276对ccRCC的诊断价值.
    结果:对TCGA和GEO数据的分析表明,ccRCC组织中CD276的mRNA表达高于癌旁组织(P<0.05)。IHC和RT-PCR的临床验证证实,ccRCC组织中CD276的表达高于癌旁组织,在mRNA和蛋白质水平(P<0.05)。ELISA显示ccRCC患者中CD276的表达高于正常人,病理分级较高的患者外周血CD276的表达高于病理分级较低的患者(P<0.05)。从上述三个数据集绘制的ROC曲线表明,CD276对ccRCC具有较高的诊断价值(AUC分别为.894,.795,.938)。
    结论:ccRCC组织中CD276的表达较高,且与病理分级呈正相关。因此,CD276可作为ccRCC预测的分子生物标志物。
    OBJECTIVE: This study aimed to explore the relationship between CD276 and clear cell renal carcinoma (ccRCC) and assess the diagnostic value of CD276 in ccRCC.
    METHODS: Expression levels of CD276 in ccRCC and para-cancer tissues were compared and analyzed retrospectively using data obtained from TCGA and GEO databases. The clinical data was analyzed prospectively. Immunohistochemistry and RT-PCR analyses were used to analyze the expression of CD276 at the mRNA and protein levels. These analyses compared the expression between ccRCC tissues and para-cancer tissues obtained from 70 patients with ccRCC. Next, ELISA was used to analyze peripheral blood samples from 70 patients with ccRCC and 72 healthy individuals, facilitating the differentiation of ccRCC patients from normal controls. Finally, we utilized the Kaplan-Meier method to generate ROC curves for assessing the diagnostic value of CD276 for ccRCC.
    RESULTS: Analysis of TCGA and GEO data revealed that the mRNA expression of CD276 was higher in ccRCC tissues than in para-cancer tissues (P < .05). Clinical validation using IHC and RT-PCR confirmed that the expression of CD276 was higher in ccRCC tissues than in para-cancer tissues, both at the mRNA and protein levels (P < .05). ELISA demonstrated that the expression of CD276 was higher in ccRCC patients than in normal individuals, and patients with a higher pathological grade showed higher expression of CD276 in the peripheral blood than those with a lower pathological grade (P < .05). ROC curves drawn from the above three datasets demonstrated that CD276 had a high diagnostic value for ccRCC (AUC = .894, .795, .938, respectively).
    CONCLUSIONS: The expression of CD276 was higher in ccRCC tissues and positively associated with the pathological grade. Therefore, CD276 may serve as a molecular biomarker for ccRCC prediction.
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  • 文章类型: Journal Article
    背景:微小RNA是乳腺癌研究中新的诊断标记和治疗靶点。miR-107和miR-126已被报道与乳腺癌的发病机制有关。本研究调查了miR-107和miR-126在乳腺癌患者中的表达水平,以发现它们与Amritsar乳腺癌风险的相关性。旁遮普,印度西北部。材料和方法:总计,200个科目,100名乳腺癌患者和100名对照者,采用定量逆转录聚合酶链反应(RT-PCR)技术筛选miR-107和miR-126的表达。Livak方法(2-ΔΔCt)用于计算微小RNA表达的倍数变化。使用学生t检验来计算与对照相比患者中miRNA表达的显著变化。进行Spearman秩相关系数和ROC。p<0.05的值被认为指示统计学上显著的差异。结果:与对照组相比,乳腺癌患者的miR-107下调(倍数变化=0.467;p=0.114),但无统计学意义。miR-126的表达在乳腺癌患者中升高了5.37倍,特别是在I期和III期患者中(p=0.009),与对照组相比,这可能表明其致癌活性。ROC分析显示miR-126可能是一个潜在的诊断标记。总之,miR-126的致癌行为提示其在乳腺癌患者的发病机制中的作用。
    Background: Micro RNAs are new diagnostic markers and therapeutic targets in breast cancer research. miR-107 and miR-126 have been reported to be linked with the pathogenesis of breast cancer. The present study investigates the levels of expression of miR-107 and miR-126 in patients with breast cancer to find their correlation with the risk of breast cancer in Amritsar, Punjab, Northwest India. Material and Methods: In total, 200 subjects, 100 patients with breast cancer and 100 controls, were enrolled to screen the expression of miR-107 and miR-126 using quantitative reverse transcription polymerase chain reaction (RT-PCR) technique. The Livak method (2-ΔΔCt) was used to calculate the fold change of the expression of micro RNAs. Student t-test was used to calculate the significant change in the expression of miRNAs in patients as compared with controls. Spearman rank correlation coefficient and ROC were conducted. The value of p < 0.05 was considered to indicate a statistically significant difference. Results: miR-107 was downregulated in patients with breast cancer as compared with controls (fold change = 0.467; p = 0.114) but not statistically significant. The expression of miR-126 was found to be 5.37 times elevated in patients with breast cancer, specifically in stage I and stage III patients (p = 0.009), compared with controls, which may indicate its oncogenic activity. The ROC analyses revealed that miR-126 could be a potential diagnostic marker. In conclusion oncogenic behavior of miR-126 is suggestive of its role in pathogenesis in patients with breast cancer.
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  • 文章类型: Journal Article
    滤泡性甲状腺癌(FTC)通过其侵入肿瘤囊和血管的能力来识别,尽管协调这种表型的确切分子信号仍然难以捉摸。在这项研究中,FTC的空间转录景观通过侵袭性前沿和组织学惰性中央核心肿瘤区域之间的比较进行了详细说明。Visium空间基因表达平台使我们能够在福尔马林固定的石蜡包埋(FFPE)组织切片中以2D询问和可视化整个转录组。对FTC的四个不同的6×6毫米区域进行了仔细检查,包括包膜和血管侵犯的区域,无入侵的胶囊附近区域,和肿瘤的中央核心区域。成功捕获和测序后,确定了几个具有区域差异的表达簇。最值得注意的是,侵袭性肿瘤细胞簇显著过表达与细胞外基质(ECM)重塑和上皮-间质转化(EMT)相互作用的通路相关的基因.这些基因的子集(POSTN和DPYSL3)在独立的滤泡性甲状腺肿瘤队列中使用免疫组织化学进行了额外验证,显示了从肿瘤核心到外周的清晰梯度模式。此外,进化树的重建将侵袭性克隆鉴定为滤泡性甲状腺肿瘤发生的晚期事件.据我们所知,这是迄今为止使用该平台的FTC的第一个2D全局转录映射之一。侵袭性FTC克隆以逐步方式发展,并显示出与ECM和EMT相关的基因的显着失调-因此突出了重要的分子串扰以供进一步研究。
    Follicular thyroid carcinoma (FTC) is recognized by its ability to invade the tumor capsule and blood vessels, although the exact molecular signals orchestrating this phenotype remain elusive. In this study, the spatial transcriptional landscape of an FTC is detailed with comparisons between the invasive front and histologically indolent central core tumor areas. The Visium spatial gene expression platform allowed us to interrogate and visualize the whole transcriptome in 2D across formalin-fixated paraffin-embedded (FFPE) tissue sections. Four different 6 × 6 mm areas of an FTC were scrutinized, including regions with capsular and vascular invasion, capsule-near area without invasion, and a central core area of the tumor. Following successful capturing and sequencing, several expressional clusters were identified with regional variation. Most notably, invasive tumor cell clusters were significantly over-expressing genes associated with pathways interacting with the extracellular matrix (ECM) remodeling and epithelial-to-mesenchymal transition (EMT). Subsets of these genes (POSTN and DPYSL3) were additionally validated using immunohistochemistry in an independent cohort of follicular thyroid tumors showing a clear gradient pattern from the core to the periphery of the tumor. Moreover, the reconstruction of the evolutionary tree identified the invasive clones as late events in follicular thyroid tumorigenesis. To our knowledge, this is one of the first 2D global transcriptional mappings of FTC using this platform to date. Invasive FTC clones develop in a stepwise fashion and display significant dysregulation of genes associated with the ECM and EMT - thus highlighting important molecular crosstalk for further investigations.
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  • 文章类型: Journal Article
    发现潜在的致病基因可以帮助医学进步。后基因组时代使这项任务变得更加困难。现代高通量方法尚未解决识别疾病基因的问题。常规方法不能用于研究许多罕见或致命疾病。使用微阵列技术监测不同样品中的基因表达值是鉴定致病基因的最佳和最准确的方法之一。实验分子生物学的最新进展之一是微阵列,这使得研究人员能够同时监测数千个基因的表达水平。微阵列数据的统计分析可以通过揭示与靶基因相关的途径和促进候选基因的鉴定来帮助基因发现。系统生物学,跨学科的方法,已经成为一种至关重要的分析工具,有可能揭示以前未知的人类疾病的原因和后果。遗传,环境,免疫学,或神经因素与癌症等复杂疾病的发展有关。正因为如此,从新的角度研究这种疾病是很重要的。系统生物学方法使我们能够快速识别致病基因并评估其作为治疗靶标的可行性。本章演示了使用公共数据库识别候选基因的系统生物学方法。口腔鳞状细胞癌(OSCC)被用作模型疾病,以显示如何成功地使用系统生物学来识别和优先考虑疾病基因。
    The discovery of potential disease-causing genes can aid medical progress. The post-genomic era has made this a more difficult task. Modern high-throughput methods have not solved the problem of identifying disease genes. Conventional methods cannot be used to investigate many rare or lethal diseases. Monitoring gene expression values in different samples using microarray technology is one of the best and most accurate ways to identify disease-causing genes. One of the most recent advances in experimental molecular biology is microarrays, which allow researchers to simultaneously monitor the expression levels of thousands of genes. Statistical analysis of microarray data might aid gene discovery by revealing pathways related to the target gene and facilitating identification of candidate genes. Systems biology, an interdisciplinary approach, has emerged as a crucial analytic tool with the potential to reveal previously unidentified causes and consequences of human illness. Genetic, environmental, immunological, or neurological factors have been implicated in the developing complex disorders like cancer. Because of this, it is important to approach the study of such disease from a novel perspective. The system biology approach allows us to rapidly identify disease-causing genes and assess their viability as therapeutic targets. This chapter demonstrates systems biology approaches to identify candidate genes using public database. Oral squamous cell carcinoma (OSCC) is used as a model disease to show how systems biology can be used successfully to identify and prioritize disease genes.
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  • 文章类型: Journal Article
    揭示lncRNACCDC144NL-AS1在CRC中的调控机制hsa-miR-143-3p,下游蛋白HMGA2相互作用臂,与临床病理特征相关。使用60例CRC患者和30例对照的外周血作为液体活检。qRT-PCR检测CCDC144NL-AS1和hsa-miR-143-3p的表达水平。CCDC144NL-AS1表达在CRC患者血清中显著上调,与更差的CRC临床病理特征有关的肿瘤浸润深度以及肿瘤3期和4期与2期和4期之间的高度显著差异相关。同时,与对照组相比,CRC患者的hsa-miR-143-3p表达下调4.5倍(p<0.0001),CRC患者的HMGA2比对照组19.59ng/μL和5.377ng/μL增加,(p<0.0001),肿瘤3期和4期以及肿瘤2期和4期之间存在显着差异。与肿瘤大小较小的CRC患者相比,肿瘤大小较大的CRC患者显示CCDC144NL-AS1表达和HMGA2水平上调(p值分别为0.0365和0.013)。CCDC144NL-AS1与HMGA2呈正相关,而lncRNACCDC144NL-AS1和hsa-miR-143-3p呈负相关。结论:作为相互作用臂,CCDC144NL-AS1/hsa-miR-143-3p/HMGA2与CRC阶段2-4相关。因此,这种相互作用臂表达在临床和计算机上获得批准,将在不久的将来指导治疗精度。
    Unravel the regulatory mechanism of lncRNA CCDC144NL-AS1 in CRC hsa-miR-143-3p, downstream protein HMGA2 interaction arm, association with clinicopathological characteristics. Using peripheral blood as liquid biopsy from 60 CRC patients and 30 controls. The expression levels of CCDC144NL-AS1 and hsa-miR-143-3p detected by qRT-PCR. CCDC144NL-AS1 expression was significantly upregulated in CRC patients\' sera, associated with worse CRC clinicopathological features regarding the depth of tumor invasion and highly significant difference between tumor stages 3 and 4 and tumor stages 2 and 4. While, hsa-miR-143-3p expression was downregulated in CRC patients by 4.5-fold change when compared to the control subjects (p < 0.0001) and HMGA2 increased in CRC patients than controls 19.59 ng/μL and 5.377 ng/μL, respectively (p < 0.0001) with significant difference between tumor stages 3 and 4 as well as tumor stages 2 and 4. CRC patients with large tumor size showed upregulation in CCDC144NL-AS1 expression and HMGA2 levels compared to those with small tumor size (p-value = 0.0365 and 0.013, respectively). CCDC144NL-AS1 and HMGA2 were positively correlated, whereas lncRNA CCDC144NL-AS1 and hsa-miR-143-3p were negatively correlated. Conclusion: As an interaction arm CCDC144NL-AS1/hsa-miR-143-3p/HMGA2 were correlated to CRC stages 2-4. Therefore, this interaction arm expression clinically and in silico approved, would direct treatment precision in the near future.
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  • 文章类型: Case Reports
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  • 文章类型: Case Reports
    小细胞肺癌(SCLC)中的几种转录因子,包括achaete-scute同源物1(ASCL1)和神经源性分化因子1(NEUROD1),有助于肿瘤的快速生长和早期转移扩散。最近的研究表明,这些分子亚型代表了动态SCLC进化中的神经内分泌分化。在目前的情况下,1名62岁男性患者被诊断患有源自右上叶的局限性疾病SCLC.活检标本ASCL1阳性,而NEUROD1阴性。同步放化疗和预防性颅骨照射后六个月,原发肿瘤已经再生,并进行了挽救性手术.病理诊断为SCLC复发,术后组织病理学检查为ASCL1和NEUROD1阳性。随后对患者进行了随访;然而,术后9个月出现多发骨转移.据推测,同步放化疗存活的肿瘤细胞向NEUROD1高表达的转变可能与联合治疗后的不良预后有关。
    Several transcription factors in small cell lung cancer (SCLC), including achaete-scute homolog 1 (ASCL1) and neurogenic differentiation factor 1 (NEUROD1), contribute to rapid tumor growth and early metastatic dissemination. Recent studies suggested that these molecular subtypes represent neuroendocrine differentiation in dynamic SCLC evolution. In the present case, a 62-year-old man was diagnosed with limited disease SCLC originating from the right upper lobe. Biopsy specimens were positive for ASCL1 but negative for NEUROD1. Six months after concurrent chemoradiotherapy and prophylactic cranial irradiation, the primary tumor had regrown and salvage surgery was performed. The pathological diagnosis was recurred SCLC, and postoperative histopathology was positive for both ASCL1 and NEUROD1. The patient was subsequently followed up; however, he had multiple bone metastases 9 months after surgery. It was speculated that the shift to NEUROD1-high expression in tumor cells surviving concurrent chemoradiation therapy may be related to the poor outcome after combined modality treatment.
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  • 文章类型: Journal Article
    环状RNA(CircRNAs)已被报道在各种癌症的进展中起关键作用,包括甲状腺癌(TC)。转录因子1(SP1)促进甲状腺癌的发展。这项研究旨在研究Circ0005654与转录因子1(SP1)联合在TC患者中的表达水平,以用于诊断和治疗目的。共有76例甲状腺癌患者接受了根治性手术。术中,收集甲状腺癌组织和配对的癌旁组织及相应的临床病理资料。通过免疫组织化学(IHC)确定甲状腺癌和癌旁组织中SP1和β-catenin的表达,而通过半定量实时聚合酶链反应(sqRT-PCR)测量Circ0005654的表达水平。然后,我们比较了Circ0005654,SP1和Wnt/β-catenin在癌组织和癌旁组织中表达的变异性,并确定了相关分析与甲状腺癌患者临床病理特征之间的关系。借助受试者工作特征(ROC)曲线分析Circ0005654在甲状腺癌组织中的诊断价值,计算术后3年生存率,分析Circ0005654和SP1蛋白水平对患者3年生存率的影响。sqRT-PCR显示Circ0005654在甲状腺癌组织中的表达程度明显高于癌旁组织。Circ0005654的ROC下面积为0.9553,95%置信区间:(0.9211-0.9895),截止值为0.7895,灵敏度为92.11%,特异性为86.84%。免疫组化结果显示,SP1、β-catenin、癌组织中Wnt高于癌旁组织;Circ0005654、SP1、Wnt/β-catenin表达水平与肿瘤直径、淋巴结转移,TNM阶段,和包膜侵入(所有P<0.05)。根据Circ0005654在甲状腺癌组织中的表达水平,高表达组3年生存率为77.5%,低表达组3年生存率为94.4%,差异有统计学意义;SP1阳性和阴性患者3年生存率分别为78.6%和100%,分别,数据明显不同。Circ0005654可作为甲状腺癌诊断的潜在生物标志物,并可能参与甲状腺癌的发展。
    Circular RNAs (CircRNAs) have been reported to play key roles in the progression of various cancers, including thyroid cancer (TC). Transcription factor 1 (SP1) promotes the development of thyroid cancer. This study aims at investigating the expression level of Circ0005654 in combination with Transcription factor1 (SP1) in patients with TC for diagnostic and therapeutic purposes. A total of 76 patients with thyroid cancer underwent radical surgery. Intraoperatively, thyroid cancer tissues and paired adjacent tissues and the corresponding clinicopathological data were collected. The expression of SP1 and β-catenin in thyroid cancer and adjacent tissues was determined by immunohistochemistry (IHC) while the Circ0005654 expression level was measured by semiquantitative real-time polymerase chain reaction (sqRT-PCR). Then, we compared the variability of Circ0005654, SP1, and Wnt/β-catenin expression in cancerous and adjacent tissues and determined the relationship between the correlation analysis and the clinicopathological features of the thyroid cancer patients. The diagnostic value of Circ0005654 in thyroid cancer tissues was analyzed with the help of the receiver operating characteristic (ROC) curve, counting the 3-year postoperative survival rate, and analyzing the effect of Circ0005654 and SP1 protein levels on the 3-year survival rate of the patients. sqRT-PCR showed that the expression level of Circ0005654 in thyroid cancer tissue was significantly higher than that of adjacent tissues. The area under the ROC of Circ0005654 was 0.9553, 95% confidence interval: (0.9211-0.9895) with a cutoff value of 0.7895, a sensitivity of 92.11%, and a specificity of 86.84%. The IHC results showed that the expression level of SP1, β-catenin, and Wnt was higher in cancer tissues than in adjacent tissues; Circ0005654, SP1, Wnt/β-catenin expression levels were associated with tumor diameter, lymph node metastasis, TNM stage, and envelope invasion (all P < .05). According to the Circ0005654 expression level in thyroid cancer tissue, the 3-year survival rate of the high expression group was 77.5% and 94.4% in the low expression group with a statistically significant difference; the 3-year survival rate of SP1 positive and negative patients was 78.6% and 100%, respectively, with the data being significantly different. Circ0005654 may serve as a potential biomarker for thyroid cancer diagnosis and may be involved in the development of thyroid cancer.
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  • 文章类型: Journal Article
    多形性胶质母细胞瘤(GBM)是一种侵袭性癌症,可导致患者高死亡率。细胞凋亡进程的中断是该病的主要病发机制之一。最近,LncRNAs和miRNAs已被证明在细胞凋亡过程中起着重要作用。为了遵循学习的目的,100名患者参加了两组50人,包括50例GBM患者和50例健康个体作为对照组。从外周血样品中分离单核细胞并进行RNA提取。miR-17-5p的表达变化,miR-20-5p,在两组中使用RT-PCR检测LINC01605、FAS-AS1和Caspase3。LINC01605,miR-20-5p,miR-17-5p在患者中增加,Caspase3和FAS-AS1降低,两组间差异有统计学意义。此外,发现这些因素作为诊断标志物具有适当的敏感性和特异性。最后,建议使用LINC01605,FAS-AS1,miR-20-5p,miR-17-5p,和Caspase3作为GM患者的凋亡预测因子。
    Glioblastoma multiform (GBM) is an invasive cancer that causes high mortality in patients. Disruption of the apoptosis process is one of the main pathogenesis of the disease. Recently, LncRNAs and miRNAs have been shown to play an important role in the process of apoptosis. To follow the aim of study, 100 patients participated in the two groups of 50 individuals, including 50 GBM patients and 50 healthy individuals as the control group. Mononuclear cells were isolated from peripheral blood samples and RNA extraction was done. The expression changes of miR-17-5p, miR-20-5p, LINC01605, FAS-AS1, and Caspase 3 were examined using RT-PCR in both groups. Expression of LINC01605, miR-20-5p, and miR-17-5p increased in patients, while Caspase 3 and FAS-AS1 decreased; the difference was statistically significant between the two groups. In addition, it was found that these factors have the appropriate sensitivity and specificity as diagnostic markers. Finally, It is suggested to use the LINC01605, FAS-AS1, miR-20-5p, miR-17-5p, and Caspase 3 as apoptosis predictors in the GM patients.
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