胃癌组织与血清miR-126的表达及临床意义

目的：分析胃癌患者癌组织与血清miR-126的表达水平,探讨胃癌组织与血清miR-126在胃癌诊断中的价值。方法：收集42对胃癌组织及其对应的远癌对照组织（距离癌组织5 cm以上）为实验组,60例年龄相近的健康人群作对照组,标本系胃癌根治术后新鲜标本,采集患者术前、术后1周及健康对照组人群的外周血各5 mL,采用实时定量PCR法检测miR-126在癌组织和患者血清中的表达情况,另采集患者术前、术后1周的外周血各5 mL送检验科做癌胚抗原（CEA）检测。根据组织及血清中miR-126检测结果和CEA值作ROC曲线判断诊断效率。结果：胃癌组织miR-126的相对表达水平低于远癌对照组织（t=7.276,P < 0.05）;miR-126在癌组织中的表达与肿瘤大小、临床分期、组织分化程度有关;在胃癌患者血清中,术前血清miR-126的相对表达水平低于术后（t=6.316,P < 0.05）;术后血清中的相对表达水平低于健康对照者（t=4.338,P < 0.05）;miR-126在血清中的表达与肿瘤临床分期、组织分化程度有关;胃癌组织miR-126的诊断效率ROC曲线下面积（AUC）为0.823,血清AUC为0.776,CEA的诊断效率AUC为0.537。Pearson相关分析显示,胃癌患者癌组织与术前血清中miR-126的相对表达水平呈正相关（r=0.484,P < 0.01）。结论：胃癌组织和血清中miR-126表达下调;血清miR-126可以作为评估胃癌患者病情严重程度的标志之一;血清miR-126的表达对胃癌具有较好的诊断价值,优于血清CEA;胃癌组织和血清miR-126的表达水平呈正相关,有望成为诊断早期胃癌和监测胃癌复发的生物学标志物。     

miR-155参与缺氧诱导的乳腺癌化疗耐药

摘 要：［目的］ 探讨miR-155在缺氧诱导的乳腺癌化疗耐药中的作用。［方法］ 以0、50、100、150、200μmol/L不同浓度CoCl2处理4T1细胞,建立缺氧模型。实时定量PCR检测缺氧条件下miR-155的表达与耐药基因BCRP的表达。通过慢病毒载体转染使miR-155过表达,通过caspase 3/9分光光度法探讨miR-155在缺氧环境下乳腺癌化疗耐药中的作用。［结果］ 随缺氧程度的增加,miR-155及BCRP基因表达增加,过表达miR-155可抑制阿霉素诱导的4T1细胞的凋亡。［结论］ 随着乳腺癌缺氧程度加重,miR-155表达逐渐增加,miR-155表达与乳腺癌化疗耐药相关。     

miR-155侧翼序列rs767649A/T多态性与结直肠癌的相关性分析

摘 要：［目的］分析miR-155侧翼序列rs767649A/T多态性与结直肠癌的相关性。［方法］ 收集154例结直肠癌和203名健康对照人群外周静脉血样本,TaqMan探针法分析rs767649A/T多态性。［结果］ TT基因型显著增加了结直肠癌的发病风险（TT与AA相比：OR=2.11,95%CI：1.12～3.98,P=0.02;TT与AA/AT相比：OR=1.92,95%CI：1.09～3.38,P=0.02）。与A等位基因对比,T等位基因显著增加了结直肠癌的发病风险（OR=1.40,95%CI：1.04～1.90,P=0.03）。分层分析显示,rs767649A/T多态性与结直肠癌临床分期、分化程度和淋巴结转移等临床特征均无关。［结论］　miR-155侧翼序列rs767649A/T多态性可能是结直肠癌发病的危险因素。     

血清miR-375、miR-155与原发性肝癌临床分期及预后的关系

目的 探讨原发性肝癌患者血清miR-375、miR-155与其临床分期及预后的关系。方法 回顾性分析86例原发性肝癌患者资料,比较不同临床分期患者血清miR-375、miR-155表达水平,应用Spearman相关系数分析相关性;将患者以肝外转移分成转移组、非转移组,比较两组患者血清miR-375、miR-155差异,应用受试者曲线(ROC)分析两者诊断临床分期效能;随访1年内生存情况,应用Kaplan-Meier法、COX比例风险模型进行生存分析。结果 不同临床分期患者血清miR-375、miR-155表达水平比较差异有统计学意义(P<0.05);血清miR-375表达水平与肿瘤临床分期呈负相关(P<0.05),miR-155表达水平与临床分期呈正相关(P<0.05);转移组血清miR-375表达水平低于非转移组,miR-155表达水平高于非转移组,差异有统计学意义(P<0.05);血清miR-375、miR-155及联合诊断肿瘤转移的AUC分为0.898、0.847、0.941;miR-375高表达患者平均生存时间均长于miR-375低表达患者,miR-15...     

胃癌患者血清中miR-106a的表达及其临床意义

目的 探讨胃癌患者血清miR 106a表达及其与临床病理特征之间的关系。方法采用实时定量RT-PCR方法检测21例胃癌患者及10例健康人血清中miR-106a表达的水平。结果 实时定量RT-PCR方法能够检测到血清样本中微量miRNA的表达。21例胃癌患者miR-106a表达水平的中位数为0.34（0.17～0.69）,10例健康人为0.63（0.27～1.0）,两者差异有统计学意义（P=0.002）。在21例胃癌患者中,血清miR-106a表达水平与肿瘤分化程度有关,在低分化胃癌中的表达水平明显高于中分化胃癌（P=0.01）;血清miR-106a表达水平亦与血清CA724相关（P=0.03）,而与分期、性别、年龄无关（P＞0.05）。结论 采用实时定量RT PCR方法检测血清中miR-106a的表达敏感可靠。血清miR-106a作为新的生物学指标对于胃癌的诊断具有一定的价值。     

结肠癌组织中miR-155表达在预测复发转移中的价值及其与血清CEA的相关性

目的 分析结肠癌组织中miR-155表达与血清CEA的相关性,探讨miR-155表达在预测复发转移中的价值。方法 收集84例结肠癌标本及对应的癌旁组织,检测肿瘤组织及癌旁组织中miR-155的表达水平,同时检测患者术前血清CEA水平。对患者进行2年的随访,随访期间每两月检测一次血清CEA。结果 与癌旁组织比较,miR-155在结肠癌组织中表达显著增高(P＜0. 05);癌组织中miR-155的表达与术前血清CEA水平呈明显正相关（P＜0.01）;癌组织中miR-155的表达与术后CEA水平再次增高的时间呈明显的负相关（P＜0.01）;复发转移组癌组织中miR-155表达水平为6.06±3.73倍,显著高于未复发转移组癌组织中miR-155表达水平3.62±2.55倍（P＜0.05）;术后血清CEA水平再次增高的时间与术后肿瘤的复发转移明显相关（P＜0.05）。结论 结肠癌组织中miR-155表达显著上调,联合检测结肠癌组织中miR-155表达与术前术后血清CEA水平可以为临床诊断、预后判断提供更加准确的信息,尤其在预测术后肿瘤的复发转移中有重要的价值。     

miR-155在MALT淋巴瘤组织中的表达及其与预后的关系

目的:探讨miR-155在MALT淋巴瘤组织中的表达及其与预后的关系。方法:收集2007年3月至2014年3月首次就诊于河北工程大学附属医院的36例均经病理证实为MALT淋巴瘤患者的带瘤组织和瘤旁组织（距瘤＞2 cm）,qPCR法检测MALT淋巴瘤患者瘤组织和瘤旁组织中miR-155表达水平,入选患者均给予标准CHOP方案化疗治疗8个周期,根据实体瘤疗效评价标准,将患者分为有效组和无效组,对比观察两组患者血清中miR-155表达水平;通过门诊或打电话方式对患者进行随访,以miR-155表达水平的平均值为阈值将治疗后患者分为miR-155高表达组（23例）和miR-155低表达组（13例）,对比观察两组患者3年生存率。结果:36例MALT淋巴瘤患者瘤组织和瘤旁组织中miR-155表达水平分别为6.63±0.70、1.29±0.05,两者差异具有统计学意义（P<0.05）;CHOP方案治疗8个周期后,有效组和无效组患者血清中miR-155表达水平分别为2.21±0.14、7.01±0.54;随访发现,治疗后miR-155高表达组和miR-155低表达组患者3年生存率分别为56.5%和76.9%,以上差异均具有统计学意义（P<0.05）。结论:miR-155表达水平可能与MALT淋巴瘤发生发展及预后有关。     

血清miR-21、miR-155与炎症因子水平在肺癌患者围手术期感染中的变化及其临床意义

目的 探究血清miR-21和miR-155与炎症因子在肺癌患者围手术期感染时水平变化及其临床意义.方法 选取肺癌患者94例,根据《医院感染诊断标准》将患者分为感染组(n=28)和非感染组(n=66).收集患者临床资料,RT-PCR检测miR-21和miR-155水平,比较2组的临床病理特征以及miR-21、miR-15...     

乳腺癌中miR-221、miR-222表达水平对GATA3和FOXA1蛋白的影响及其作用机制

目的： 探讨乳腺癌中miR-221和miR-222（miR-221/222）表达水平对GATA结合蛋白3（GATA3）和叉头框蛋白A1（FOXA1）表达的影响及其作用机制。方法： 收集汕头大学医学院附属肿瘤医院2020年1月—2021年5月经手术切除的86例乳腺浸润性导管癌及其癌旁组织标本,分别采用茎环引物实时荧光定量PCR（qPCR）和免疫组织化学方法检测癌组织和相应癌旁组织中miR-221/222的表达水平及GATA3、FOXA1蛋白的表达水平,分析其与临床病理指标的关系。进一步在5种乳腺癌细胞系（MCF-7、T47D、SKBR3、MDA-MB-231和BT-549）中转染miR-221/222 mimics后,采用qPCR检测各细胞中miR-221/222的表达水平;采用Western blot检测转染后MCF-7细胞中GATA3、FOXA1、雌激素受体-α（ER-α）和钙黏蛋白E（E-cadherin）的表达;用细胞划痕和迁移侵袭实验检测转染后MCF-7细胞修复和迁移侵袭能力。结果： 在乳腺癌组织中,miR-221/222的表达水平明显高于癌旁正常乳腺组织（P=0.00）。miR-221/222表达水平在FOXA1、GATA3、ER-α及孕激素受体（PR）阴性表达组均显著高于阳性表达组（P<0.01）;在Her-2阳性和高表达Ki-67的乳腺癌中较Her-2阴性和低表达Ki-67组显著升高（P<0.05）;在三阴性和Her-2阳性亚型乳腺癌中显著高于Luminal A和Luminal B1型乳腺癌（P=0.00）;而miR-221/222水平与患者年龄、月经状况、肿瘤大小、组织学分级、淋巴结转移及TNM分期无显著相关关系（P>0.05）。在5种乳腺癌细胞系中,miR-221/222在MCF-7细胞中均低表达。与对照组相比,在MCF-7细胞中瞬时转染miR-221/222 mimics后miR-221/222表达显著升高（P<0.05）,且内源性的GATA3和FOXA1蛋白表达被抑制（P<0.01）,上皮细胞相关分子ER-α和E-cadherin表达显著下降（P<0.01）;划痕修复能力和迁移侵袭能力均显著增强（P<0.01）。结论： miR-221/222可能通过下调GATA3和FOXA1的表达促进乳腺癌的迁移和侵袭。     

乳腺癌患者血浆中三种microRNA的表达水平分析

  目的  分析乳腺癌患者血浆、血清中三种microRNA（miRNA）的表达水平,探讨血浆、血清中miRNA表达水平之间关系以及血浆中miRNA作为乳腺癌肿瘤标志物的可行性。  方法  于2010年12月至2011年3月间收集符合入选条件的31例患者的血液标本,分离血浆、血清,提取其中miRNA,通过定量PCR,检测其中miR-31、miR-155及miR-200c表达水平。  结果  三种miRNA在血清、血浆中表达水平基本相同;乳腺癌患者血浆中的miR-155较非乳腺癌表达上调,miR-200c表达下调;两组间miR-31表达差异无统计学意义;miR-155的表达与肿瘤的大小、淋巴结转移、临床病理分期、ER、PR表达状态有关;miR-200c的表达与肿瘤的大小、淋巴结转移、临床病理分期、ER表达状态有关,与PR的表达状态无关;miR-31的表达与肿瘤的大小有关,与淋巴结转移、临床病理分期、ER、PR表达状态无关。  结论  乳腺癌患者血清、血浆中三种miRNA的表达水平相同;血浆中三种miRNA的表达与乳腺癌的临床病理特征密切相关,因此血浆中miRNA有望成为乳腺癌新一代的肿瘤标志物。      

Analysis of miR-205 and miR-155 expression in the blood of breast cancer patients

The purpose of this study was to identify and validate circulating microRNAs (miRNAs) in human plasma for use as breast cancer (BC) biomarkers and to analyze their relationship to clinicopathologic features and its preliminary biological function. Genome-wide expression profiling of miRNAs in BC was investigated by microarray analysis. miR-155 was up-regulated greater than two-fold in BC compared with Normal Adjacent Tissue (NAT), whereas let-7b, miR-381, miR-10b, miR-125a-5p, miR-335, miR-205 and miR-145 were down- regulated greater than two-fold. Our hypothesis was that circulating miRNAs are also present and differentially expressed in the serum of BC patients compared to controls. Using real-time PCR (RT-PCR), we analyzed miR-205 and miR-155 in archived serum from 30 participants, 20 with breast cancer and 10 healthy people. miR-205 was down-regulated in BC patient serum while miR-155 was up-regulated. Furthermore, we analyzed the relationship between the expression levels of these two miRNAs and the clinicopathologic parameters of BC patients. High expression of miR155 was associated with clinical stage, molecular type, Ki-67 and p53 in BC patients (P<0.05). By contrast, we found no significant correlation between miR-205 and BC patient clinicopathologic parameters. Functional analysis showed that ectopic expression of miR-205 significantly inhibits cell proliferation and promotes apoptosis. miR-205 was down-regulated and miR-155 was up-regulated in BC patient serum. miR-155 was positive correlated with clinical stage and ki-67 and negatively correlated with p53 status.     

miR-155 increases stemness and decitabine resistance in triple-negative breast cancer cells by inhibiting TSPAN5

Effective therapeutic targets for triple-negative breast cancer (TNBC), a special type of breast cancer (BC) with rapid metastasis and poor prognosis, are lacking, especially for patients with chemotherapy resistance. Decitabine (DCA) is a Food and Drug Administration-approved DNA methyltransferase inhibitor that has been proven effective for the treatment of tumors. However, its antitumor effect in cancer cells is limited by multidrug resistance. Cancer stem cells (CSCs), which are thought to act as seeds during tumor formation, regulate tumorigenesis, metastasis, and drug resistance through complex signaling. Our previous study found that miR-155 is upregulated in BC, but whether and how miR-155 regulates DCA resistance is unclear. In this study, we demonstrated that miR-155 was upregulated in CD24⁻CD44⁺ BC stem cells (BCSCs). In addition, the overexpression of miR-155 increased the number of CD24⁻CD44⁺ CSCs, DCA resistance and tumor clone formation in MDA-231 and BT-549 BC cells, and knockdown of miR-155 inhibited DCA resistance and stemness in BCSCs in vitro. Moreover, miR-155 induced stemness and DCA resistance by inhibiting the direct target gene tetraspanin-5 (TSPAN5). We further confirmed that overexpression of TSPAN5 abrogated the effect of miR-155 in promoting stemness and DCA resistance in BC cells. Our data show that miR-155 increases stemness and DCA resistance in BC cells by targeting TSPAN5. These data provide a therapeutic strategy and mechanistic basis for future possible clinical applications targeting the miR-155/TSPAN5 signaling axis in the treatment of TNBC.     

Circulating tumor markers in breast cancer: Accepted utilities and novel prospects

Detecting and/or monitoring changes in circulating tumor markers might assist in evaluating cancer risk, diagnosis, prognosis, or response to treatment. Several categories of circulating tumor markers have been investigated in breast cancer. These categories include classical tumor-associated antigens, such as CEA and CA 15-3, markers of tumor biology, including markers of angiogenesis, adhesion, and invasion, and antibody response to tumor-associated antigens such as HER2/neu and p53. We used a recently proposed Tumor Marker Utility Grading System to evaluate the use of several circulating tumor markers for different clinical utilities in breast cancer. While there are no tumor markers with established clinical utilities for most uses, tumor-associated antigens can be used for monitoring patients with metastatic disease. In addition, markers of tumor biology such as the circulating extracellular domain of HER2/neu might be useful in determining not only prognosis, but also response to specific treatments. However, further investigations are required to further assess the utility of individual tumor markers for specific clinical uses.     

MiR-34b和miR-155在非小细胞肺癌中的表达及临床意义

目的:检测肺癌组织及癌旁正常组织中miR-34b和miR-155的表达水平及其与肺癌临床病理特征之间的关系。方法:收集50例非小细胞肺癌患者的肺癌组织和癌旁正常肺组织标本,运用 Real-time PCR检测 miR-34b和miR-155在肺癌组织和癌旁正常肺组织中的表达情况,分析其表达与肺癌临床病理特征之间的关系。结果:Real-time PCR 检测显示在50例非小细胞肺癌组织中 miR-34b的表达显著低于癌旁正常肺组织(P=0.019),而miR-155的表达显著高于癌旁正常肺组织(P=0.000)。MiR-34b和miR-155的表达与淋巴结转移情况显著相关（P均＜0.05,miR-34b呈负相关,miR-155呈正相关）;与性别、年龄、病理类型及肿瘤分化程度无明显相关;miR-34b的表达与临床病理分期无显著相关,而miR-155表达与临床病理分期显著相关。结论:MiR-34b和miR-155的异常表达与非小细胞肺癌的发生发展相关,其可能成为肺癌的筛查、诊断及治疗的肿瘤标志物。     

Inhibition of hypoxia-induced miR-155 radiosensitizes hypoxic lung cancer cells

miR-155 is a prominent microRNA (miRNA) that regulates genes involved in immunity and cancer-related pathways. miR-155 is overexpressed in lung cancer, which correlates with poor patient prognosis. It is unclear how miR-155 becomes increased in lung cancers and how this increase contributes to reduced patient survival. Here, we show that hypoxic conditions induce miR-155 expression in lung cancer cells and trigger a corresponding decrease in a validated target, FOXO3A. Furthermore, we find that increased levels of miR-155 radioprotects lung cancer cells, while inhibition of miR-155 radiosensitizes these cells. Moreover, we reveal a therapeutically important link between miR-155 expression, hypoxia, and irradiation by demonstrating that anti-miR-155 molecules also sensitize hypoxic lung cancer cells to irradiation. Our study helps explain how miR-155 becomes elevated in lung cancers, which contain extensive hypoxic microenvironments, and demonstrates that inhibition of miR-155 may have important therapeutic potential as a means to radiosensitize hypoxic lung cancer cells.     

Clinical significance of serum miR-21 in breast cancer compared with CA153 and CEA

Objective： MicroRNA-21 （miR-21） has been shown to be a key regulator of carcinogenesis. There were few reports about the comparison of serum miR-21 with conventional tumor markers. This study aimed to explore the diagnostic value of circulating miR-21 as a tumor marker in breast cancer （BC） and compare it with CA15 3 and carcinoembryonic antigen （CEA）. Methods： Circulating miR-16 and miR-21 were amplified and quantitatively detected by real-time PCR in 89 BC patients and 55 healthy controls. The levels of CA153 and CEA were measured through assays. Then the sensitivity in diagnosis of BC was compared among miR-21, CA153 and CEA. Results： The level of serum miR-21 was significantly higher in BC patients than controls （P〈0.001）. The sensitivity and specificity of miR-21 were 87.6% and 87.3%, respectively, whereas the sensitivities of CEA and CA153 were only 22.47% and 15.73%. Con~lusions： Compared with CEA and CA153, serum miR-21 has a higher sensitivity in diagnosis of BC. Although not correlated with the status of ER, PR and clinical stages, serum miR-21 may be a potential diagnostic indicator for BC, especially for the early stage.     

Quantitation of circulating DNA in the serum of breast cancer patients by real-time PCR

The purpose of this study was to quantify the level of serum DNA in different groups of primary breast cancer patients and in healthy controls using real-time quantitative PCR in order to determine whether such measurements have diagnostic or prognostic value. A total of 96 serum samples of patients with primary breast cancer before surgery (with positive or negative lymph nodes and with high or low relapse-free survival) as well as 24 healthy controls were analysed. DNA concentrations in the serum of the patients differed significantly from the concentration of serum DNA in the controls (medians were 221 and 63 ng x ml(-1), respectively, P<0.001 M-W test). However, no statistically significant difference was observed between the patient groups (P=0.87, M-W test). The serum DNA levels were elevated independently of the size of primary tumour or lymph node metastases. The overall survival of patients with serum DNA concentrations >221 ng x ml(-1) was better than patients with serum DNA concentration 相似文献   

Prognostic significance of serum c-erbB-2 protein in breast cancer patients

Summary The tissue expression of c-erbB-2 protein in breast cancer is a marker of poor prognosis in a number of studies. More recently it has also been suggested that c-erbB-2 expression may predict response to systemic therapy in patients with advanced breast cancer. The measurement of c-erbB-2 protein in the serum of breast cancer patients has now been reported, but the significance of this finding is not clear. In this study an ELISA assay was used to measure c-erbB-2 in the sera of 23 normal controls, 46 benign breast disease patients, and 119 breast cancer patients. Elevated serum c-erbB-2 protein levels were detected in 13% (3/23) of normal controls, 15% (7/46) of benign disease patients, 15% (7/46) of Stage I/II patients, 26% (9/35) of Stage III patients, and 21% (8/38) of Stage IV patients. The tissue expression of the c-erbB-2 protein showed no association with detection of the serum c-erbB-2 protein (p = 0.31). In the 67 Stage III and IV patients who had assessable disease the presence of the c-erbB-2 protein in the serum bore no relationship to response to hormonal therapy (p = 0.71). Serum detection of the c-erbB-2 protein in Stage I/II patients predicted for a worsening of both survival outcome (p = 0.002) and disease free interval (p = 0.002). A worse outcome was also seen for the Stage III patients (p = 0.04) and Stage IV patients, although the latter did not reach statistical significance (p = 0.27).This study found that the presence of c-erbB-2 in the serum of breast cancer patients was of prognostic significance for all stages of disease.