微小RNA-214在胰腺癌中的表达及临床意义研究

背景与目的：微小RNAs(microRNAs,miRNA,miR)在多种肿瘤中异常表达,可能与肿瘤的发生、发展、侵袭及转移有关,被认为可能起癌基因或抑癌基因的作用。该研究旨在检测miR-214在胰腺癌组织中的表达情况,并探讨其临床意义。方法：实时定量PCR(real-time PCR,RT-PCR)法检测36例胰腺癌组织与相应癌旁组织中miR-214的表达水平,分析miR-214表达水平与胰腺癌患者临床病理特征及预后的关系。结果：miR-214在69.4%(25/36)的胰腺癌组织中相对高表达,表达水平为3.45(1.73~5.13),癌旁组织中的表达水平为1.52(1.09~2.12),差异有统计学意义(P＜0.01),并且在T3、T4期患者中的表达水平显著高于T1、T2期患者(P=0.018)。Kaplan-Meier生存分析显示,miR-214表达水平越高,患者生存期越短(P=0.032)。结论：miR-214在胰腺癌组织中的表达上调与胰腺癌的临床病理特征及患者预后密切相关,miR-214可能成为胰腺癌诊断及预后判断的新的分子标志。     

肝细胞癌患者外周血中miR-30a、miR-106b的表达及其与预后的关系

目的:探讨肝细胞癌(hepatocellular carcinoma,HCC)患者血清miR-30a、miR-106b的表达及其与 预后的关系。方法:选取2015年6月-2017年2月本院收治的HCC患者80例为研究对象,20例同期健康人群作为对照组。荧光定量PCR检测外周血中miR-30a、miR-106b的表达水平,分析患者血清miR-30a、miR-106b水平与HCC临床病理的关系。分析HCC患者预后的影响因素以及血清miR-30a、miR-106b水平与HCC患者预后的相关性。结果:HCC患者血清miR-30a表达水平（1.03±0.02）低于正常人群（5.15±0.06）（P=0.00）;血清miR-106b表达水平（2.62±0.35）高于正常人群（1.15±0.06）（P=0.00）。miR-30a、miR-106b表达与患者肿瘤直径、组织分化类程度、肝内转移、淋巴结转移、甲胎蛋白（AFP）水平、门静脉癌栓、肿瘤数目及TNM分期有显著相关性(P＜0.05) 。miR-30a低表达组患者3年总生存率（39.8%）低于miR-30a高表达组（64.6%）（P=0.002）;miR-106b低表达组患者3年总生存率（75.8%）高于miR-106b高表达组（51.2%）（P=0.003）。二元Logistic回归分析提示,淋巴结转移、TNM分期、miR-106b及miR-30a水平是患者预后的重要影响因素。结论:miR-30a在HCC患者血清中低表达,miR-106b在HCC患者血清中高表达,与肿瘤的进展、预后不良有关。     

宫颈癌组织miR-199b表达及其临床意义的初步分析

目的：研究miR-199b在宫颈癌组织中的表达及其临床意义。方法：利用实时定量PCR方法检测miR-199b在35例宫颈癌组织中的表达情况;采用x2检验分析miR_199b表达水平与各临床病理参数之间的关系;用Kaplan-Meier法分析miR-199b表达与宫颈癌患者生存期之间的关系。结果：与癌旁组织相比较,在35例肿瘤组织中,27例miR-199b高表达。miR-199b低表达患者平均生存时间为54．38个月（95％CI：42．90～65．85）,miR-199b高表达患者平均生存时间33．48个月（95％CI：25．75～41．20）。miR-199b在宫颈癌组织中的表达水平与患者的无进展生存率明显相关,P=0．031。结论：miR-199b表达高的患者预后较差。miR-199b可能是预测宫颈癌预后的标志。     

结肠癌患者血清中miR-30a、miR-106b的表达及其临床意义

目的:探讨结肠癌患者血清miR-30a、miR-106b的表达及其在结肠癌进展及预测患者预后中的价值。方法:选取2012年06月至2013年02月本院收治的接受结肠癌手术治疗的患者80例为研究对象,20例同期健康人群作为对照组。逆转录 PCR法检测外周血血清中 miR-30a、miR-106b的表达水平,分析患者血清miR-30a、miR-106b表达与结肠癌临床病理及预后的关系。Spearman分析miR-30a、miR-106b表达的相关性。采用多因素logistic回归模型对结肠癌患者的预后影响因素进行分析,采用Kaplan-Meier生存分析miR-30a低表达组、miR-30a高表达组,miR-106b低表达组、miR-106b高表达组患者中位生存时间。结果:结肠癌患者血清miR-30a表达水平（1.03±0.02）低于正常人群（5.15±0.06）,差异具有统计学意义（t=16.38,P=0.01）;结肠癌患者血清miR-106b表达水平（2.62±0.35）高于正常人群（1.15±0.06）,差异具有统计学意义（t=10.17,P=0.03）。miR-30a、miR-106b表达与患者的组织分化类型、浆膜侵犯、淋巴结转移、远处转移、TNM分期有显著相关性(P＜0.05)。多因素logistic回归模型对结肠癌患者预后影响因素进行分析,TNM分期（Ⅲ+Ⅳ）、miR-106b高表达及miR-30a低表达是结肠癌患者预后不良的危险因素。miR-30a低表达组患者总体生存时间（55.3±4.1）个月低于miR-30a高表达组（76.4±2.4）个月（P=0.000）;miR-106b低表达组患者的总体生存时间（75.1±7.3）个月高于miR-106b高表达组（51.8±3.1）个月（P=0.000）。结论:miR-30a在结肠癌患者血清中低表达,miR-106b在结肠癌患者血清中高表达,二者的表达与肿瘤的进展、预后不良有关。     

miR－199b在人结直肠癌中的表达及其与患者临床病理特征和预后的关系

目的探讨miR-199b与结直肠癌患者临床病理特征以及预后的关系。方法收集2011年3—12月于中国医学科学院肿瘤医院接受治疗的202例结直肠癌患者的癌组织及癌旁正常组织, 采用实时荧光定量PCR方法检测结直肠癌组织及相应癌旁正常组织中miR-199b的表达水平, 生存分析采用Kaplan-Meier法和Log rank检验, 受试者工作特征(ROC)曲线评估miR-199b预测结直肠癌患者预后的价值。结果结直肠癌组织中miR-199b的相对表达水平(-7.88±0.11)低于癌旁正常组织(-6.49±0.12, P<0.001)。伴有淋巴结转移的结直肠癌组织中miR-199b的表达水平(-7.51±0.14)高于无淋巴结转移的结直肠癌组织(-8.23±0.17, P<0.001)。miR-199b在Ⅰ～Ⅱ期、Ⅲ期和Ⅳ期结直肠癌组织中相对表达水平逐渐升高, 分别为-8.26±0.17、-7.70±0.16、-6.57±0.27, 差异有统计学意义(P<0.001)。miR-199b高表达组患者的5年生存率(75.6%)低于低表达组患者(84.6%, P=0.045)。...     

miR-873抑制肝细胞癌的侵袭与迁移

目的:检测miR-873在肝细胞癌(hepatocellular carcinoma,HCC)中的表达情况,探究其与HCC临床病理特征及HCC病人预后的相关性,进一步探究其对HCC细胞侵袭与迁移的影响.方法:应用Real-time PCR法检测90例HCC组织和对应癌旁组织中miR-873的表达水平;应用统计学方法分析miR-873的表达水平与HCC临床病理特征的相关性及对HCC病人预后的影响;应用Real-time PCR法检测HCC细胞系中miR-873的表达水平,并应用Transwell小室实验探究miR-873对HCC细胞侵袭与迁移能力的影响.结果:miR-873在90例HCC组织中的表达水平较癌旁组织显著下调(P<0.05);miR-873的表达水平与肿瘤数目、静脉侵犯、Edmondson病理分级及TNM分期显著相关(P<0.05);Kaplan-Meier曲线分析发现,miR-873低表达的患者生存率较差(P<0.05),且miR-873可作为肝癌病人术后生存的独立预测指标;miR-873在HCC细胞系中(Hep3B、MHCC-97H、HepG2、SMMC-7721)的表达较正常肝细胞LO2显著下调(P<0.05);Transwell小室实验显示miR-873能显著抑制HCC细胞的侵袭与迁移能力.结论:miR-873在HCC中表达下调,与HCC的临床病理及HCC病人的预后相关,并且能够抑制HCC细胞的侵袭与迁移能力.     

miR-335、Survivin表达及对乳腺癌术后患者预后评估的价值

目的:探讨微小RNA335(microRNA-335,miR-335)和Survivin在乳腺癌患者组织中表达情况以及其表达水平对患者预后的影响。方法:收集我院2010年2月1日至2014年2月1日乳腺癌患者标本140例,通过实时免疫荧光定量聚合酶链反应（RT-PCR)法检测所有乳腺癌组织、癌旁组织中miR-335的表达情况;采用免疫组织化学方法检测癌组织、癌旁组织中Survivin的表达情况。应用SPSS 16.0软件对比miR-335、Survivin与乳腺癌患者临床病理之间的关系,以及对患者预后的影响。结果:miR-335在癌组织中的表达明显低于癌旁组织(25.36% vs 82.51%,P=0.003),Survivin在癌组织中的表达明显高于癌旁组织(80.13% vs 26.73%,P=0.001 6),miR-335在乳腺癌组织中的表达水平与肿瘤病理类型、分化程度、临床分期呈负相关（r=-0.47,P=0.02;r=-0.31,P=0.03;r=-0.75,P=0.04),而Survivin在乳腺癌组织中的表达水平与肿瘤病理类型、分化程度、临床分期呈正相关（r=0.52,P=0.03;r=0.63,P=0.01;r=0.37,P=0.03)。COX回归模型发现乳腺癌患者肿瘤TNM分期、淋巴结转移、分化程度、病理类型、ER、PR、Her-2、miR-335、Survivin表达均为影响乳腺癌患者PFS的因素。miR-335对于乳腺癌患者术后3年 PFS、OS预测曲线下面积分别为83.4%、78.6%(P<0.01);Survivin 对于乳腺癌患者术后3年PFS、OS预测曲线下面积分别为79.5%、70.6%(P<0.01)。差异有统计学意义（P<0.01,P<0.01)。结论:miR-335、Survivin在乳腺癌组织和癌旁正常组织中的表达存在明显差异,miR-335高表达、Survivin低表达时,提示乳腺癌患者手术预后良好。     

microRNA-21 预测食管癌放疗敏感性和预后的意义

目的:探讨食管癌中microRNA-21（miR-21）表达水平与放疗敏感性和预后的关系。方法:收集在我院接受放疗的食管癌患者60例,采用RT-PCR方法检测miR-21的相对表达量,并分析其与临床病理特征、放疗疗效和预后的相关性。结果:miR-21的表达水平与肿瘤大小、淋巴结和远处转移明显相关(P＜0.05)。在60例食管癌患者中,CR、PR和NC组患者中miR-21的表达水平分别为1.56±0.35、2.82±0.84和3.31±1.32,miR-21的表达水平与食管癌的放疗敏感性呈负相关(P＜0.05)。Kaplan-Meier分析显示miR-21低表达组放疗后的生存时间明显高于高表达组,差异有显著统计学意义(P＜0．05)。结论:肿瘤组织中miR-21表达量可作为评价食管癌放疗敏感性和预后的预测指标。     

高表达DNAJA1促进乳腺癌细胞增殖及侵袭且与患者的不良预后及化疗抵抗密切相关

目的:分析DNAJ热休克蛋白40家族成员A1［DNAJ heat shock protein 40 family（Hsp40) member A1,DNAJA1］在人乳腺癌组织中的表达及其与患者临床病理特征的关系,探讨DNAJA1对乳腺癌细胞增殖及侵袭的影响,揭示其与乳腺癌患者预后及化疗抵抗的关系。方法:免疫组织化学检测169例乳腺癌患者配对石蜡组织及120例接受新辅助化疗前穿刺活检石蜡组织中DNAJA1的表达情况。CCK-8、平板克隆、Transwell侵袭及细胞划痕实验检测DNAJA1对乳腺癌细胞增殖和侵袭的影响。结果:DNAJA1在原发灶及转移灶的乳腺癌组织中的表达明显高于癌旁组织（P＜0.001,P＜0.001）。临床病理分析发现,DNAJA1的高表达与分子分型、p53的突变和肿瘤复发密切相关。DNAJA1高表达还与患者的较短生存时间相关（P=0.023）。另外,DNAJA1在接受新辅助化疗的Miller-Payne（MP) 5级组患者的癌组织中表达明显低于其他组（P=0.000 4）。体外实验证实,敲低DNAJA1能明显抑制乳腺癌细胞的增殖和侵袭。结论:DNAJA1能促进乳腺癌细胞的增殖和侵袭,且DNAJA1在乳腺癌组织中高表达与患者不良预后及化疗抵抗相关,可作为预测患者预后及新辅助化疗效果的一个新靶点。     

不同级别人胶质瘤组织中miR-10b表达变化的研究

背景与目的:人miR-10b编码基因位于染色体2q31HOXD8基因之间,有研究显示其特异性地高表达于多种肿瘤中,并与肿瘤的侵袭、迁移和远距离转移有关。本研究对不同级别胶质瘤组织及非肿瘤对照脑组织中miR-10b的表达水平进行检测和比较。方法:采用组织微阵列及锁定寡核苷酸原位杂交技术检测56例不同级别胶质瘤及10例非肿瘤对照脑组织中miR-10b的表达水平。结果:对照脑组织及WHOⅠ~Ⅱ级、Ⅲ级及Ⅳ级胶质瘤组织中miR-10b阳性标记指数(LI%)分别为36.87±20.63、18.86±14.04、12.13±11.56及4.93±6.45,4组间差异均有显著性(P<0.05~0.001),miR-10b LI%与肿瘤的良恶性分级呈显著负相关(rs=-0.61,P<0.001)。结论:miR-10b的表达水平与胶质瘤病理分级呈负相关。     

miR-20b is up-regulated in brain metastases from primary breast cancers

Brain metastases are frequent in patients with advanced breast cancer and are associated with poor prognosis. However, unique molecular biomarkers have not yet been established. We hypothesized that microRNA-20b (miR-20b) plays a role in breast cancer brain metastasis. Our study cohort comprised of eleven breast cancer patients with brain metastasis and nine control patients (age, stage, and follow-up matched) with breast cancer without brain metastasis. Cases were reviewed microscopically to select tumor blocks with >50% tumor cells, RNA was extracted from formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks and expression of miR-20b analyzed using qRT-PCR. We further tested the effect of miR-20b overexpression on colony formation and invasion in vitro using MCF-7 and MDA-MB-231 cells. In the patient-derived samples, miR-20b expression was significantly higher in brain metastases of breast cancer patients, compared to primary breast tumors as well as the patients without brain metastasis. miR-20b also significantly induced the colony formation and invasiveness of breast cancer cells. Further, miR-20b levels were observed to be high in brain-metastasizing cells, compared to bone-metastasizing cells. Together, our findings suggest a novel role of miR-20b in breast cancer brain metastasis that warrants further investigation for its potential to be developed as prognostic and/or therapeutic target.     

DNA hypermethylation of microRNA-34b/c has prognostic value for stage Ⅰ non-small cell lung cancer

Lung cancer is the leading cause of cancer-related death in the world and approximately 30-40% of patients with stage Ⅰ non-small cell lung cancer (NSCLC) die of recurrent disease. miRNA expression profiles can be diagnostic and prognostic markers of lung cancer. Recently, miR-34 family has been shown to be part of the p53 pathway which is frequently involved in lung cancer, and the expression of miR-34 has been reported to be regulated by DNA methylation. In present study, we investigated the correlation between DNA methylation status of miR-34 family and recurrence of stage Ⅰ NSCLC patients. miR-34a and miR-34b/c promoter methylation status were determined by nested methylation-specific PCR in FFPE tumor tissues from 161 patients of stage Ⅰ NSCLC. Furthermore, mature miR-34b and miR-34c expression were analyzed by qRT-PCR in the same panel tissues. Our results revealed that aberrant DNA methylation of miR-34b/c was correlated with a high probability of recurrence (p = 0.026) and associated with poor overall survival (p = 0.010) and disease-free survival (p = 0.017). No significant association was found for miR-34a methylation. Multivariate analysis showed that promoter hypermethylation of miR-34b/c was an independent prognostic factor of stage Ⅰ NSCLC. Moreover, no significant association between mature miR-34b and miR-34c expression and DNA methylation status was found. In conclusion, we have identified promoter hypermethylation of miR-34b/c as a relatively common event in NSCLC and might be a potential prognostic factor for stage Ⅰ NSCLC.     

组织miR-193b表达及甲基化状态对前列腺癌患者术后骨转移的预测价值北大核心

目的:探究组织miR-193b表达及甲基化状态对前列腺癌(prostate cancer,PCa)患者术后发生骨转移的预测价值。方法:回顾性分析2016年09月至2018年07月期间在我院首次接受根治性前列腺切除术的154例患者,将骨转移作为本研究的主要研究终点,比较组织miR-193b表达及其甲基化状态与PCa患者发生骨转移的相关性。结果:骨转移组肿瘤组织miR-193b相对表达量低于非骨转移组,同时miR-193b基因启动子甲基化率高于非骨转移组(P<0.05)。miR-193b基因启动子甲基化组织中miR-193b相对表达量较非甲基化组织降低(P<0.05)。经Pearson法分析,肿瘤组织中miR-193b表达和基因启动子甲基化呈负相关性(r=-0.45,P<0.05)。经单因素和多因素Logistic回归分析,bGS>7分、cTx:T_(3)-T_(4)、tPSA水平升高、组织miR-193b基因启动子甲基化都是影响PCa患者发生骨转移的独立危险因素。经受试者工作特征曲线分析,组织miR-193b表达预测PCa患者发生骨转移的AUC为0.912(95%CI:0.863~0.960)。结论:miR-193b基因启动子高甲基化是PCa患者术后发生骨转移的独立危险因素,且肿瘤组织中miR-193b表达与基因启动子甲基化状态呈负相关性,因此检测组织miR-193b表达可用于预测PCa患者术后骨转移风险。     

MicroRNA-30a inhibits cell migration and invasion by downregulating vimentin expression and is a potential prognostic marker in breast cancer

Tumor recurrence and metastasis result in an unfavorable prognosis for cancer patients. Recent studies have suggested that specific microRNAs (miRNAs) may play important roles in the development of cancer cells. However, prognostic markers and the outcome prediction of the miRNA signature in breast cancer patients have not been comprehensively assessed. The aim of this study was to identify miRNA biomarkers relating to clinicopathological features and outcome of breast cancer. A miRNA microarray analysis was performed on breast tumors of different lymph node metastasis status and with different progression signatures, indicated by overexpression of cyclin D1 and β-catenin genes, to identify miRNAs showing a significant difference in expression. The functional interaction between the candidate miRNA, miR-30a, and the target gene, Vim, which codes for vimentin, a protein involved in epithelial-mesenchymal transition, was examined using the luciferase reporter assay, western blotting, and migration and invasion assays. The association between the decreased miR-30a levels and breast cancer progression was examined in a survival analysis. miR-30a negatively regulated vimentin expression by binding to the 3'-untranslated region of Vim. Overexpression of miR-30a suppressed the migration and invasiveness phenotypes of breast cancer cell lines. Moreover, reduced tumor expression of miR-30a in breast cancer patients was associated with an unfavorable outcome, including late tumor stage, lymph node metastasis, and worse progression (mortality and recurrence) (p < 0.05). In conclusion, these findings suggest a role for miR-30a in inhibiting breast tumor invasiveness and metastasis. The finding that miR-30a downmodulates vimentin expression might provide a therapeutic target for the treatment of breast cancer.     

Circulating miR-148b and miR-133a as biomarkers for breast cancer detection

Circulating microRNAs have drawn a great deal of attention as promising novel biomarkers for breast cancer. However, to date, the results are mixed. Here, we performed a three-stage microRNA analysis using plasma samples from breast cancer patients and healthy controls, with efforts taken to address several pitfalls in detection techniques and study design observed in previous studies. In the discovery phase with 122 Caucasian study subjects, we identified 43 microRNAs differentially expressed between breast cancer cases and healthy controls. When those microRNAs were compared with published data from other studies, we identified three microRNAs, including miR-148b, miR-133a and miR-409-3p, whose plasma levels were significantly higher in breast cancer cases than healthy controls and were also significant in previous independent studies. In the validation phase with 50 breast cancer cases and 50 healthy controls, we validated the associations with breast cancer detection for miR-148b and miR-133a (P = 1.5×10⁻⁶ and 1.3×10⁻¹⁰, respectively). In the in-vitro study phase, we found that both miR-148b and miR-133a were secreted from breast cancer cell lines, showing their secretory potential and possible tumor origin. Thus, our data suggest that both miR-148b and miR-133a have potential use as biomarkers for breast cancer detection.     

Concordant HER2 status between metastatic breast cancer cells in CSF and primary breast cancer tissue

It is not known whether the HER2 status of malignant CSF cells coincides with that of the original breast carcinoma cells. We investigated whether CSF cytology specimens were suitable to evaluate HER2 status by fluorescence in situ hybridization (FISH) in patient with leptomeningeal metastasis (LM). Both formalin-fixed paraffin-embedded (FFPE) breast cancer tissue and liquid based CSF cytology specimens were evaluated for HER2 status in 16 patients with LM. We evaluated HER2 gene amplification using FISH on destained CSF cytology slides containing a minimum of 20 malignant cells per slide, and compared these with the HER2 status by immunohistochemistry (IHC) or FISH in FFPE tissues. HER2 was considered positive when the HER2:CEP17 ratio was ≥2.0 or IHC 3+. Of 16 cases, four were HER2 positive and 12 were HER2 negative by FISH analysis in CSF cytology. All CSF-positive cases were HER2 positive by IHC in FFPE tissue. Of 12 HER2 FISH-negative cases in CSF cytology, 10 were HER2 negative (IHC 0 or 1+) and two were IHC 2+ in FFPE tissue. Two IHC 2+ cases had HER2:CEP17 ratios of 1.27 and 2.1, respectively, by FISH in FFPE tissue. As a result, the HER2 status concordance rate between metastatic breast cancer cells in CSF and FFPE primary tissue by IHC and FISH was very high. When CSF cytology specimens were appropriately prepared and had adequate cellularity without dry artifacts, the CSF cytology was suitable to evaluate HER2 status by FISH analysis in patients with LM.     

Down Regulated Expression Levels of miR-27b and miR-451a as a Potential Biomarker for Triple Negative Breast Cancer Patients Undergoing TAC Chemotherapy

Background: Triple negative breast cancer (TNBC) is associated with poor prognosis, aggressive phenotype(s) of tumours, partial chemotherapy response, and lack of clinically proven therapies. MicroRNAs (miRNAs) can target and modulate key genes that are involved in TNBC chemotherapy. Deregulated miRNA expression is highly involved in anti-cancer drug resistance phenotype and thus, miRNAs tend to be promising candidates for prediction of chemotherapy response and recurrence. Aim: This study aimed to investigate the expression levels of selected miRNAs (miR-21, miR-27b, miR-34a, miR-182, miR-200c and miR-451a) in cancerous and normal adjacent tissues of TNBC patients and to correlate with the clinicopathological data. Methods: Forty-one (41) FFPE tissue block of histopathologically confirmed TNBC patients was collected. Total RNA from the cancerous and adjacent non-cancerous tissues were isolated, transcribed, and pre-amplified. The relative expression level of miRNAs in tumour and normal adjacent tissues of TNBC patients was analysed using qRT-PCR. Results: Out of six miRNAs studied, the relative expression of miR-27b and miR-451a were found to be significantly lower in cancerous as compared to normal adjacent tissues of TNBC patients. In addition, a significant down regulation of miR-451a was also observed in infiltrating ductal carcinoma subtype, stages I and II, in both grade II and III, premenopausal and postmenopausal as well as in those with positive axillary lymph node metastases. Conclusion: The results suggest the possible utilization of miR-27b and miR-451a expression levels as potential predictive risk markers for TNBC patients undergoing TAC chemotherapy.     

miR-129对乳腺癌肿瘤干细胞自我更新能力的调控作用及其机制探讨

目的:探究miR-129在乳腺癌中对肿瘤干细胞自我更新能力的调控作用及其机制。方法:应用免疫组化检测乳腺癌肿瘤干细胞在肿瘤组织与癌旁组织中的数量及其与乳腺癌肿瘤分期的关系,验证miR-129和Numb与乳腺癌肿瘤干细胞之间的相关关系。在体外实验中应用Western Blotting及RT-PCR验证miR-129通过阻断雌激素受体alpha（ER alpha,ESR1）对Notch信号通路的调节作用及其调节的具体机制;应用裸鼠成瘤实验验证miR-129在裸鼠体内水平对乳腺癌肿瘤干细胞的影响。结果:肿瘤组织中乳腺癌肿瘤干细胞的比例高于癌旁组织并与肿瘤分期具有相关性;乳腺癌肿瘤干细胞比例与临床样本中miR-129和Numb的表达水平呈负相关;乳腺癌肿瘤干细胞中miR-129的过表达与Notch信号通路的抑制直接相关,这种作用很可能是miR-129通过调控ESR1所引起的Let-7b的表达下调进而导致Numb的释放来实现的;miR-129在裸鼠体内实验中可以抑制乳腺癌肿瘤干细胞的成瘤。结论:miR-129在乳腺癌组织中可以通过调控Notch信号通路影响乳腺癌肿瘤干细胞自我更新的能力,具体的调节机制可能是通过调控ESR1所引起的Let-7b的表达下调进而导致Numb的释放来最终抑制Notch信号通路的激活。     

膀胱尿路上皮癌石蜡包埋组织中miR-20a的表达与复发的相关性分析

目的 探讨膀胱尿路上皮癌(膀胱癌)石蜡包埋组织中提取microRNA的可行性,分析miR-20a在膀胱癌石蜡包埋组织中的表达情况与临床病理特征及术后复发的关联性。方法 荧光定量RT-PCR法检测50例新鲜膀胱癌组织和对应的石蜡包埋组织中miR-20a基因表达的相关性,分析不同年度间181例石蜡包埋膀胱癌组织中miR-20a基因的表达,并与患者术后复发进行相关性分析。结果 石蜡包埋膀胱癌组织与新鲜冷冻组织中miR-20a的表达密切相关（r=0.792,P＜0.001）;不同年度间石蜡组织的miR-20a表达稳定,差异无统计学意义。miR-20a表达量与肿瘤临床特征明显相关,高表达患者其术后复发明显增高（P﹤0.05）。结论 石蜡包埋膀胱癌组织与新鲜冷冻组织中miR-20a的表达有一致性,用石蜡组织提取microRNA是可行的,膀胱癌细胞中miR-20a的作用与其表达量相关,高表达是术后复发的独立因素。