miR-34b和miR-320a的表达与前列腺癌组织临床病理特征及预后的相关性

目的 探讨前列腺癌组织中miR-34b、miR-320a的表达与其临床病理特征及预后的相关性.方法 选择前列腺癌患者80例,另选40例良性前列腺增生患者作为对照组.采用定量聚合酶链式反应(RT-PCR)检测两组患者组织中miR-34b、miR-320a的表达量,分析前列腺癌组织中miR-320a、miR-34b与各临床...     

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。     

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。     

miR-193b与肿瘤相关性的研究进展

miRNAs已被证实是基因表达的关键调控因子,不同水平的表达与各种疾病相关。大多数的研究表明,miRNAs表达谱中的miR-193b参与机体多种病理生理过程,在肿瘤发生、发展过程中发挥抑癌基因的作用,可抑制肿瘤细胞增殖、迁移和侵袭能力。因此,miR-193b在疾病的诊断、治疗和预后评估等方面将会发挥更大的作用,有着广阔的应用前景。本文就miR-193b与肿瘤相关性研究进展作一综述。     

乳腺癌患者骨髓微转移与其他预后指标相关性的研究

目的:研究乳腺癌患者骨髓微转移与其他预后指标的相关性.方法:采用RT-PCR法检测了69例乳腺癌患者骨髓中CK19 mRNA的表达,并将骨髓微转移与肿瘤细胞DNA含量、细胞周期分布及增殖细胞核抗原(PCNA)、血管内皮细胞生长因子(VEGF)、HER-2和ER等指标和传统预后指标的相关性进行了研究.结果:RT-PCR技术检测乳腺癌患者骨髓微转移的阳性率为34.8%.骨髓微转移与肿瘤大小、患者年龄、月经状态及激素受体状况等指标无相关性,P0.05.骨髓微转移与腋窝淋巴结状态、HER-2过表达、VEGF水平、S期细胞比值(SPF)以及PCNA有相关性,P<0.05.在淋巴结病理学检查阴性的病例中,有17.6%的病例骨髓微转移检查阳性.结论:乳腺癌患者骨髓微转移与患者的一般临床特点无相关性,但与反映肿瘤细胞增殖、侵袭特性的大部分生物学指标具有相关性.在淋巴结病理学检查阴性的病例中,部分病例骨髓微转移阳性.     

转移性乳腺癌临床病理特征及预后分析

目的:分析单一机构转移性乳腺癌(metastatic breast cancer,MBC)患者的临床病理特征及生存情况,并探讨影响预后的独立因素.方法:研究对象为2004年1月-2006年12月乳腺癌根治术后出现复发和转移并具备完整的病历和随访资料的280例MBC患者,对其临床病理特征、复发和转移情况以及生存情况进行回顾性分析.单因素生存分析采用Kaplan-Meier法,多因素预后分析采用COX比例风险模型.结果:本组患者中位无进展生存时间(progression-free survival,PFS)为9个月(1～93个月),中位总生存时间(overall survival,OS)为45个月(2～99个月),1、3和5年生存率分别为91.1％、59.5％和36.9％.单因素分析显示,病理类型、淋巴血管侵犯、激素受体( hormonal receptor,HR)状态、分子分型、无病生存时间(disease-free survival,DFS)、内脏转移、首次转移部位数目、肝转移、脑转移、解救内分泌治疗和解救放疗与OS相关(P＜0.05).多因素分析显示,淋巴血管侵犯、分子分型、内脏转移和肝转移是MBC患者预后的独立影响因素(P＜0.05).结论:淋巴血管侵犯、三阴型乳腺癌、内脏转移和肝转移是MBC患者不良预后的独立影响因素,对MBC患者的预后判断及个体化治疗具有重要的临床指导意义.     

血管增殖与乳腺癌预后的相关性研究

目的：探讨血管增殖与乳腺癌预后的相关性。方法：采用免疫组化的方法检测78例乳腺癌标本中CD31的表达，并结合微血管计数和随访结果，用x^2检验、单因素和多因素分析进行统计学处理。结果：微血管计数较高的患者5年生存率明显低于计数低者(P＝0．0066)；肿瘤组织中高水平的血管增殖与患者无瘤生存率(RR＝3．1)和总生存率(RR=2．9)有很强的相关性。结论：肿瘤组织内血管增殖水平的高低在乳腺癌患者中是一个独立的预后指标，高水平的血管增殖的存在预示着患者可能在短期内复发或转移。     

miR-21、miR-125b与舌鳞状细胞癌患者预后生存的关系

目的 研究miR-21、miR-125b与舌鳞状细胞癌患者预后生存的关系.方法 选取86例舌鳞状细胞癌患者手术切除的癌组织与对应的癌旁正常组织,分别测定其组织中miR-21、miR-125b表达量.患者随访半年,分析miR-21、miR125b表达与患者预后生存的关系.结果 舌鳞状细胞癌组织中miR-21、miR125...     

microRNA-10b对人食管癌细胞系EC9706迁移和侵袭的影响

目的:探讨微小RNA-10b(microRNA-10b,miR-10b)对食管癌细胞系EC9706迁移和侵袭能力的影响。方法:构建pEGFP-miR-10b真核表达载体,在食管癌细胞系EC9706中稳定表达miR-10b,利用real-time PCR检测其表达水平,应用划痕试验,Transwell小室实验分析迁移和侵袭能力的改变。结果:转染miR-10b载体后,real-time PCR检测其表达水平显著高于对照组(P<0.05),miR-10b的表达能够显著促进EC9706细胞的迁移和侵袭能力(P<0.05)。结论:miR-10b能够促进食管癌细胞系EC9706的迁移和侵袭,可作为评价食管癌转移能力的指标。     

miR-10b对脑胶质瘤恶性生物学行为的调控及其机制

脑胶质瘤（胶质瘤）具有高发病率、高病死率、高复发率及低治愈率的特点,胶质瘤细胞的无限增殖能力和高侵袭迁移 能力是胶质瘤治疗的难点,近年来微小核糖核酸（microRNA,miRNA）的出现为研究胶质瘤的发生及侵袭迁移机制提供了新的思 路。miRNA是一类内生的、长约20~24个核苷酸的非编码小RNA,可通过与其靶基因mRNA的3’UTR区域互补结合,从而在转 录后水平调控基因的表达。多项研究证实,miR-10b在胶质瘤组织和胶质瘤患者血清中高表达,并影响患者预后情况。miR-10b 可能通过影响其靶基因如PTEN、CDKN、P53、HOXD10等的表达,参与胶质瘤细胞的增殖、侵袭和迁移等过程。深入研究miR- 10b对胶质瘤的调控作用及其机制,对该病的诊断、治疗和预后评估等均具有重要意义。     

miR-10b Promotes Migration and Invasion in Nasopharyngeal Carcinoma Cells

MicroRNA-10b (miR-10b) has been reported to play an important role in some types of cancer, but the effectsand possible mechanisms of action of miR-10b in the metastasis of nasopharyngeal carcinoma cells (NPC) havenot been explored. The aim of the present study was to investigate the function of miR-10b in nasopharyngealcarcinoma and to determine the molecular mechanisms underlying its action. The MTT assay was used toassess proliferation of CNE-2Z cells. Wound healing and transwell migration assays were applied to assesscell migration and invasion, while and expression of E-cadherin and MMP-9 were detected using Western blotanalysis. Real-time PCR was employed to detect the expression of genes related to migration and invasion andthe 2-ΔΔCt method was used to calculate the degree of expression. MTT assay showed the expression of miR-10bto have no effect on the proliferation of NPC cell lines. The wound healing assay showed that miR-10b mimicspromoted the mobility and invasion of NPC cell lines. Inhibitors of miR-10b reduced the ability of NPC cell linesto migrate and invade. In addition, the expression of genes related to migration and invasion, such as E-cadherin,vimentin, and MMP-9, were confirmed to be different in the CNE-2Z NPC cell line transfected with miR-10bmimics and with miR-10b inhibitors. In the present study, miR-10b was found to upregulate the expression ofMMP-9 and knockdown of miR-10b was found to significantly downregulate the expression of E-cadherin. Onthe whole, these results showed that miR-10b plays an important role in the invasion and metastasis of NPCcells.     

Differential distribution of miR-20a and miR-20b may underly metastatic heterogeneity of breast cancers

Background: The discovery that microRNA (miRNA) regulates metastasis provide a principal molecularbasis for tumor heterogeneity. A characteristic of solid tumors is their heterogenous distribution of blood vessels,with significant hypoxia occurring in regions (centers of tumor) of low blood flow. It is necessary to discover themechanism of breast cancer metastasis in relation to the fact that there is a differential distribution of crucialmicroRNA in tumors from centers to edges. Methods: Breast tissues from 48 patients (32 patients with breastcancer) were classified into the high invasive and metastatic group (HIMG), low invasive and metastatic group(LIMG), and normal group. Samples were collected from both the centers and edges of all tumors. The first sixspecimens were detected by microRNA array, and the second ten specimens were detected by real-time qRTPCRand Western blot analyses. Correlation analysis was performed between the miRNAs and target proteins.Results: The relative content of miR-20a and miR-20b was lower in the center of the tumor than at the edge in theLIMG, lower at the edge of the tumor than in the center in the HIMG, and lower in breast cancer tissues than innormal tissues. VEGF-A and HIF-1alpha mRNA levels were higher in the HIMG than in the LIMG, and levelswere higher in both groups than in the normal group; there was no difference in mRNA levels between the edgeand center of the tumor. VEGF-A and HIF-1alpha protein levels were higher in the HIMG than in the LIMG,and protein levels in both groups were higher than in the normal group; there was a significant difference inprotein expression between the edge and center of the tumor. Correlation analysis showed that the key miRNAs(miR-20a and miR-20b) negatively correlated with the target proteins (VEGF-A and HIF-1alpha). Conclusions:Our data suggest that miR-20a and miR-20b are differentially distributed in breast cancer, while VEGF-Aand HIF-1alpha mRNA had coincident distributions, and VEGF-A and HIF-1alpha proteins had uneven andopposing distributions to the miRNAs. It appears that one of the most important facets underlying metastaticheterogeneity is the differential distribution of miR-20a and miR-20b and their regulation of target proteins.     

In situ labeling apotosis in breast cancer as related to prognosis

Objective: This study was undertaken to determine the expression of apoptosis in breast cancer and to evaluate its significance as a prognostic marker. Methods: A series of 91 invasive breast cancer was analysed for the expression of apoptosis by using the 3-end-labeling method of DNA in tissue sections. The apoptotic indexes were the percentages of apoptotic cells among tumor cells. Results: The end-labeling method allowed a precise evaluation of the expression of apoptosis. Apoptosis occurred in 91.1% of breast cancer patients, and apoptotic indexes were divided into two groups, 0–0.21 and 0.28–0.62. Low apoptotic index was related to axillary lymph node metastasis (P<0.01). In survival analysis, higher apoptotic index was related to disease free survival (P=0.0095) and overall survival (P=0.0348) in the entire cohort. Cox’s analysis showed that apoptotic index had no independent prognostic value. Conclusion: The apoptosis was a spontaneous phenomenon in breast cancer tissue, and the expression was different from each other. Further analysis was needed to clarify the relationship between apoptosis and prognosis, especially the response to adjuvant therapy.     

乳腺癌根治术后单纯胸壁复发放疗和胸壁再复发的预后分析

目的:探究乳腺癌根治术后单纯胸壁复发(ICWR)患者的照射野及剂量选择,同时分析胸壁再复发的预后因素。方法:回顾性分析1998—2018年间解放军总医院第五医学中心和医科院肿瘤医院收治的乳腺癌改良根治术后ICWR患者201例,患者术后均未行辅助放疗。胸壁复发后48例(73.6%)患者接受手术治疗,155例(77.1%)...     

Quantitative ultrasound as a predictor of node metastases and prognosis in patients with breast cancer

BACKGROUND: A retrospective study was performed to determine whether preoperative quantitative ultrasound assessment could predict axillary lymph node metastases and prognosis in patients with breast cancer. We focused on the presence of a halo, which is one of the features of breast cancer on ultrasound and represents reflections from the invading margin around infiltrating malignancies. METHODS: We evaluated ultrasonography from 187 infiltrating breast carcinoma patients with tumors 5 cm or less in greatest dimension (T1, T2). Using computer image analysis, the halo area (H) and the sum of the area of halo and internal echo (total tumor area (T)) were measured, and the ratio of halo to entire tumor (H/T, halo ratio) was calculated and compared with lymph node status and prognosis. RESULTS: The mean of the halo ratio was 0.38+/-0.13. Using the value of 0.42 as a cut-off, the high halo ratio group had significantly worse prognoses for both overall and disease-free survival at 49 months in median follow-up (p <0.001 and p <0.0005, respectively). The specificity of a high halo ratio in the T1 classification for predicting axillary node metastasis was 83.1%, with a negative predictive value of 86.8%. In patients with tumors 1.0 cm or smaller, the negative predictive value was 100%. In a multivariate analysis, halo ratio was an independent predictor of disease-free survival of breast carcinoma patients (p =0.0232). CONCLUSIONS: Preoperative quantitative ultrasound may be a useful non-invasive method for predicting the presence of axillary lymph node metastases and prognosis in patients with primary breast cancer.     

Expression levels of microRNA-145 and microRNA-10b are associated with metastasis in non-small cell lung cancer

Although metastasis remains the overwhelming cause of death for patients with non-small cell lung cancer (NSCLC), the underlying mechanisms of metastasis remain unknown. Accumulating evidence suggests that microRNAs (miRNAs) are key players in the regulation of tumor cell invasion and metastasis. Expression of miR-9, miR-10b, miR-145, and miR-155, 4 miRNAs previously shown to play roles in metastasis in other tumor types, was compared in lymph node (LN)-positive NSCLC versus LN-negative NSCLC. Expression of miR-145 was significantly lower in LN-positive NSCLC (P < 0.05), while expression of miR-10b was significantly higher (P < 0.05). Expression of both miR-145 and miR-10b was correlated with lymph node metastasis in NSCLC (both Ps < 0.001). In addition, miR-10b facilitated the migration and invasion of lung cancer cell line A549, while miR-145 suppressed the migration and invasion capacity of A549 in vitro. These results suggest that miR-10b and miR-145 may act as an oncogene or tumor suppressor gene, respectively, in NSCLC metastasis.     

胃癌组织原钙黏蛋白10 mRNA表达水平与预后的相关性

背景与目的：编码原钙黏蛋白10(protocadherin-10,PCDH10)的PCDH10基因启动子甲基化与胃癌患者不良预后相关。但PCDH10表达水平与胃癌预后的关系不明确。该研究旨在分析PCDH10表达水平与胃癌预后及临床病理因素间的关系,寻找预测胃癌患者复发及死亡风险的指标。方法：采用实时荧光定量聚合酶链反应(real-time lfuorescent quantitative polymerase chain reaction,RTFQ-PCR)方法检测115对胃癌组织与相应癌旁组织PCDH10 mRNA的表达水平,分析PCDH10 mRNA的表达水平与预后及临床病理因素的关系。采用Logis-tic回归分析建立预测患者5年内复发或死亡风险的模型。结果：PCDH10 mRNA低表达组与非低表达组相比,无进展生存时间(progression-free survival,PFS)与总生存时间(overall survival,OS)显著延长(P值分别为0.046与0.033),淋巴结转移较少(P=0.001),TNM分期较早(P=0.001)。Cox单因素分析发现,Lauren分型、T分期、N分期、M分期及PCDH10 mRNA表达水平与PFS及OS显著相关。包含PCDH10作为参数的Logistic回归模型对胃癌患者术后5年内复发或死亡风险的预测效率与仅包含传统临床病理学参数的Logistic回归模型的预测效率相当。结论：PCDH10低表达胃癌患者淋巴结转移较少,TNM分期较早,预后较好,可以作为预测胃癌患者预后的辅助指标。基于PCDH10表达水平的Logistic回归模型可以在淋巴结转移情况不明时起到辅助判断患者预后的作用。     

DNA甲基化调控miRNA-328的表达水平与乳腺癌预后的关系分析

目的 探讨DNA甲基化与微小RNA-328（miR-328）表达的关系及miR-328与浸润性乳腺癌临床病理特征和预后的关系。方法 回顾性分析1998年1月至2013年12月从TCGA乳腺癌芯片数据提取的1090例浸润性乳腺癌组织和104例癌旁组织的miR-328表达水平,分析从TCGA_BRCA_hMethyl450芯片数据中获取的775例浸润性乳腺癌组织和98例癌旁组织的miR-328启动子区CpG位点（cg16421621、cg04650403）甲基化率并计算启动子区甲基化与miR-328水平的相关性,从UCSC Genome Browser中的clinical_data_dictionary芯片数据中获取854例有完整临床病理资料及随访数据的乳腺癌标本,分析miR-328表达与临床病理特征及预后的关系,采用Cox回归模型分析影响预后的因素。结果 TCGA数据库1998年1月至2013年12月有miR-328表达量的1194例乳腺癌及癌旁组织中,1090例浸润性乳腺癌组织的miR-328水平为5.224±1.155,低于104例癌旁组织的6.246±0.923,差异有统计学意义（P＜0.01）;775例浸润性乳腺癌组织的miR-328基因启动子区域cg16421621和cg04650403的甲基化率分别为（0.415±0.201）%和（0.193±0.068）%,高于98例癌旁组织的（0.407±0.222）%和（0.094±0.079）%,差异有统计学意义(P＜0.01）;浸润性乳腺癌标本中miR-328的表达量与其启动子区域CG位点（cg16421621、cg04650403）甲基化率呈负相关（r=-0.127, P=0.005）。854例有完整信息的浸润性乳腺癌患者中,miR 328表达水平与淋巴结转移和肿瘤大小有关（P＜0.05）;miR-328低表达组（＜5.462）的中位总生存时间（OS）为7.25年,低于高表达组（≥5.462）的8.75年,差异有统计学意义（P<0.01）。Cox多因素回归分析显示,年龄、淋巴结转移与miR-328表达水平为影响OS的独立因素（P＜0.05）,miR-328高表达组的危险程度低于低表达组（P＜0.01）。结论 浸润性乳腺癌中miR-328表达受其基因启动子区甲基化调控;miRNA-328与浸润性乳腺癌的临床病理特征有关,并能作为影响浸润性乳腺癌预后的危险因素。