微 RNA-21和微 RNA-146a 在结直肠肿瘤中的表达及临床意义

目的探讨结直肠肿瘤患者组织和血清中 miRNA-21和 miRNA-146a 的表达情况,并分析其临床意义。方法收集100例结直肠癌、80例结直肠腺瘤患者和65名健康对照者的内镜活检组织,同时收集其血清标本,应用实时荧光定量 PCR 检测 miRNA-21和 miRNA-146a 的表达水平,分析其表达与临床病理特征间的关系,并评估血清差异表达的 miRNA 在结直肠肿瘤诊断中的价值。组间比较采用 Mann-WhitneyU 检验和 Kruskal-Wallis 检验;Spearman 相关性检验用于分析组织和血清中 miRNA 表达的关联性。结果在结直肠癌和结直肠腺瘤患者病变组织中 miRNA-21的表达分别为8．573±0．898和7．746±1．183,显著高于健康对照者的6．160±0．835（U ＝120．129、33．230,P 均＜0．01）;在结直肠癌和结直肠腺瘤患者血清中的表达分别为1．829±0．303和1．624±0．226,也高于健康对照者的1．391±0．221（U ＝40．353、15．512,P 均＜0．01）;miRNA-21在结直肠癌患者组织中和血清中的表达均高于结直肠腺瘤患者（U＝11．384、10．189,P 均＜0．01）。miRNA-21在结直肠癌患者中的高表达与肿瘤临床分期、淋巴结转移有关;miRNA-21在结直肠腺瘤中的表达水平与病理类型有关。Spearman 分析结果示,miRNA-21在结直肠癌患者组织和血清中的表达呈正相关（r ＝0．459,P ＜0．01）。miRNA-146a 在结直肠癌患者组织中为2．556±0．351,血清中为0．249±0．038,低于健康对照者的3．428±0．328和0．279±0．053（U ＝102．134、30．111,P 均＜0．01）;其在结直肠腺瘤患者组织中为3．255±0．332,血清中为0．290±0．036,与健康对照者比较差异无统计学意义（U＝3．936、3．180,P 均＞0．05）。miRNA-146a 在结直肠癌患者组织中和血清中的表达均低于结直肠腺瘤患者（U＝73．809、21．123,P 均＜0．01）。结直肠癌患者miRNA-146a 的下降程度与肿瘤临床分期、肿瘤分化程度有关,而在结直肠腺瘤中的表达与临床特征间无明显关系。根据 ROC 曲线分析,鉴别结直肠癌与健康者,血清 miRNA-21、miRNA-146a 及二者联合检测 ROC 的 AUC 分别为0．889、0．791和0．863;鉴别结直肠腺瘤与健康者,其 AUC 分别为0．784、0．692和0．761;鉴别结直肠癌与结直肠腺瘤患者,其 AUC 分别为0．705、0．820和0．713。结论血清 miRNA-21和 miRNA-146a 的差异表达在结直肠癌的早期诊断中具有潜在的价值。     

The high expression of CHD1L and its clinical significance in human solid tumors: A meta-analysis

Background:Chromodomain helicase DNA-binding protein 1-like (CHD1L) is an oncogene. It was cloned from 1q21 chromosome region of hepatocellular carcinoma in 1991. CHD1L is up-regulated in many kinds of cancers and is involved in the carcinogenesis and development of tumors. More and more studies have shown that over-expression of CHD1L is associated with poor prognosis of tumors. The purpose of this study was to evaluate the prognostic value of CHD1L in human solid tumors.Methods:The key words in the database of PubMed, Web of Science, Embase, Cochrane library, and TCGA were searched for systematic literature retrieval. We collected relevant articles and data about CHD1L and prognosis of cancer and screened them according to the eligible criteria to evaluate the prognostic value of CHD1L in cancer patients. Then Stata SE12.0 software is used to analyze the data.Results:In our meta-analysis, 2720 patients with a total of 15 articles involving multiple types of tumors showed that high expression levels of CHD1L were associated with shorter overall survival (OS) (hazard ratio  = 2.21, 95% confidence interval [CI]: (1.49–3.30)] and (hazard ratio  = 1.16, 95% CI: (1.01–1.32)] in the TCGA database, in addition, the pooled odds ratios (ORs) indicated high expression levels of CHD1L in tumors significantly are associated with TNM stage (OR = 1.61, 95% CI: 1.01–2.55, P < .05), tumor size (OR = 1.38, 95% CI: 1.07–1.78, P < .05), tumor differentiation (OR = 2.13, 95% CI: 1.43–3.16, P < .05), and distant metastasis (OR = 1.86, 95% CI: 1.45–2.39 P < .05). However, we did not observe a significant correlation between the high expression of CHD1L and age, gender.Conclusion:The high expression of CHD1L is associated with poor OS as well as related to tumor differentiation, tumor size, and distant metastasis, which can be served as a prognostic marker and a potential predictor of clinical pathology in human solid tumors.     

微小RNA-302b在急性心肌梗死患者血清中的表达及临床意义

目的检测微小RNA-302b(miR-302b)在急性心肌梗死(AMI)患者血清中的表达,并探讨其与心肌损伤的关系。方法选取2016年陕西省第四人民医院72例AMI患者为AMI组,采用随机数字表法选取同期体检的48名健康人作为对照组。两组均通过实时荧光定量PCR法检测血清miR-302b含量(AMI组患者在临床确诊后12 h内检测),spearman法分析血清miR-302b表达与心肌酶谱的相关性。结果 miR-302b在AMI组患者血清中的相对表达量显著高于对照组(3.14±0.76比1.13±0.22,t=17.706,P<0.001);AMI患者的血清miR-302b相对表达量与天门冬氨酸氨基转移酶(r=0.428,P=0.017)、乳酸脱氢酶(r=0.519,P=0.045)、肌酸激酶同工酶(r=0.718,P=0.003)和心肌肌钙蛋白I(r=0.772,P<0.001)呈正相关。ROC曲线分析示miR-302b诊断AMI的敏感度为88.6%、特异度为64.3%。结论 miR-302b在AMI患者血清中呈高表达,并与心肌损伤相关。     

P21WAF1在胃肠道间质瘤中表达的临床及病理意义

［摘要］　目的　探讨P21^WAF1在胃肠道间质瘤(gastrointestinal stromal tumors,GIST)中表达的临床及病理意义。方法　应用免疫组化Maxvision方法检测50例GIST瘤组织中P21^WAF1的表达情况。结果　50例GIST瘤组织中P21^WAF1阳性率为48.0%,明显低于瘤旁组织阳性率76.2%。结论　P21^WAF1与GIST发生发展有关,可作为CD117外的GIST的补充指标,对于明确诊断GIST有重要意义。     

微小核糖核酸-25在胃癌患者血清中的异常表达及其临床意义

目的 探讨微小核糖核酸-25(miRNA-25)在胃癌患者血清中的异常表达及其临床意义.方法 选择第四军医大学西京医院手术及随访资料完整的胃癌(86例)、胃腺瘤(70例)患者和健康对照者(80名)为研究对象,提取血清总RNA,在建立了稳定、敏感的血清miRNA-25绝对定量检测方法(qRT-PCR)的基础上,检测胃癌、胃腺瘤患者和健康对照者血清中miRNA-25表达水平.分析胃癌、胃腺瘤和健康对照者血清中的miRNA-25表达差异及血清miRNA-25表达水平与胃癌临床病理参数的关系.结果 胃癌患者血清中miRNA-25的表达水平(135.6 fmol/μg总RNA)显著高于胃腺瘤(67.7 fmol//μg总RNA)和健康对照者(62.2 fmol/μg总RNA,P＜0.01),同时miRNA-25的受试者工作特征曲线显示,血清miRNA-25对胃癌诊断具有良好的特异度和敏感度(曲线下面积=0.827);有淋巴结转移者[(148.3±10.2)fmol/μg总RNA]和临床病理分期Ⅲ/Ⅳ期[(146.7±9.5)fmol/μg总RNA]胃癌患者血清miRNA-25的表达分别明显高于无淋巴结转移者[(120.3±10.1)fmol/μg总RNA]和Ⅰ/Ⅱ期胃癌患者[(119.4±12.2)fmol/μg总RNA](P＜0.05);相关性研究结果表明,血清miRNA-25高表达胃癌患者的生存期与血清miRNA-25低表达胃癌患者无明显差异(P＞0.05).结论 血清miRNA-25的检测可能有助于胃癌的诊断和预后预测.

Abstract：

Objective To investigate the abnormal expression of microRNA (miRNA)-25 in the serum of gastric cancer patients and its clinical significance. Methods In Xijing Hospital of Digestive Diseases,Fourth Military Medical University,86 gastric cancer patients with operation and completed follow-up data,70 gastric adenoma patients and 80 healthy controls were selected as study objects.Total RNA was isolated from the serum. After the stable and sensitive miRNA-25 absolute quantity detection method established,the serum levels of miRNA-25 in gastric carcinoma patients,gastric adenoma patients and healthy controls were tested according to this method. The expression differences of miRNA-25 in the serum of patients with gastric cancer and gastric adenoma and healthy controls were analyzed with statistic analysis,and the correlation between miRNA-25 expression level and clinic pathological features of gastric cancer was also analyzed. Results The expression level of miRNA-25 in the serum of gastric cancer patients (135. 6 fmol/μg total RNA) was significantly higher than that of gastric adenoma patients (67. 7 fmol/μg total RNA) and healthy controls (62. 2 fmol/μg total RNA)(P＜0. 01). The receiver operating characterisstic curve of miRNA-25 indicated that serum miRNA-25 with good specificity and sensitivity in gastric cancer diagnosis (AUC=0. 827). The serum level of miRNA-25 in gastric cancer patients with lymph node metastasis [(148. 3±10. 2) fmol/μg total RNA] or clinicopathological stage Ⅲ /Ⅳ patients [(146. 7±9.5) fmol/μg total RNA] was significantly higher than that of gastric cancer patients without lymph node metastasis [(120. 3±10. 1)fmol/μg total RNA] or clinicopathological stage Ⅰ/Ⅱpatients [(119. 4±12. 2) fmol/μg total RNA] (P＜0.05). The correlation statistical analysis result indicated that there was no significant difference in survival period between serum miRNA-25 highly expressed and lowly expressed gastric cancer patients (P＞0. 05).Conclusion Serum miRNA-25 testing maybe helpful in diagnosis and prognosis of gastric cancer.     

Expression and clinical significance of serum microRNA-122 in liver fibrosis of patients withchronic hepatitis B

<正>Objective To evaluate the expression of serum microRNA (miRNA)-122 in patients with chronic hepatitis B (CHB) with different stages of liver fibrosis,and to investigate its relevance to the clinical parameters.Methods Totally 138 CHB patients and 30 healthy controls were enrolled. Real-time polymerase chain reaction was used to measure the relative expression of miRNA-     

老年急性心肌梗死患者血清微小核糖核酸-302b表达及其临床意义

目的探讨血清微小核糖核酸(microRNA,miR)-302b在老年急性心肌梗死(acute myocardial infarction,AMI)患者中的表达及其临床意义。方法选取海南三林旅业开发有限公司澄迈富力红树湾医院内科和海南省人民医院收治的136例老年AMI患者和50例正常对照组,比较两组血清miR-302b、心肌肌钙蛋白I(myocardial troponin I,cTnI)及肌酸激酶同工酶(creatine kinase isoenzyme,CK-MB)浓度变化。应用受试者工作特征曲线(receiver operating characteristic curve,ROC)分析血清miR-302b、cTnI及CK-MB浓度对老年AMI患者诊断的价值。结果AMI组血清miR-302b(4.19±1.27 vs.0.48±0.14,P<0.01)、cTnI[(3.14±1.32)ng/mL vs.(0.03±0.01)ng/mL,P<0.01]及CK-MB[(73.42±19.20)U/L vs.(11.64±2.18)U/L,P<0.01]均明显高于对照组,差异有统计学意义。ROC分析结果显示,miR-302b、cTnI及CK-MB诊断AMI的临界值分别为2.64、1.48 ng/mL、60.75 U/L,3项联合诊断老年AMI的曲线下面积=0.933(95%CI:0.870~0.982)最大,其敏感度和特异度为94.6%和89.0%。结论血清miR-302b在老年AMI患者中呈高表达,与cTnI、CK-MB联合检测有助于提高老年AMI诊断的准确性。     

microRNA-145在肝细胞肝癌中的表达及临床意义

[目的]探讨肝细胞肝癌中microRNA-145(miR-145)水平的变化及其临床意义。[方法]采用实时荧光定量PCR(qRT-PCR)检测30例肝癌组织、癌旁组织及3例正常肝组织中miR-145表达量,以及Hep G2肝癌细胞、L-O2胎肝细胞中miR-145表达量并计算miR-145相对表达量。结合采集组织的性别、年龄、淋巴结转移、肿瘤大小、HBV感染、AFP浓度等临床病理参数分析miR-145表达水平有无明显差异。[结果]肝癌组织中miR-145表达明显低于正常肝组织,差异有统计学意义(P0.05),癌旁组织与正常肝组织及肝癌组织之间表达差异无统计学意义(均P0.05),Hep G2细胞中miR-145表达明显低于L-O2细胞,差异有统计学意义(P0.05)。miR-145在肝癌中的表达异常与性别、年龄、淋巴结转移、肿瘤大小、HBV感染、AFP浓度无相关,差异无统计学意义。[结论]miR-145在肝癌患者中低表达,在肿瘤发生发展过程中可能担任了抑癌基因的角色,对肝细胞肝癌的临床诊断有意义。     

系统性红斑狼疮患者血清卵泡抑素样蛋白1表达水平及其临床意义

目的 检测系统性红斑狼疮(SLE)患者血清中卵泡抑素样蛋白1(FSTL1)的水平及FSTL1在狼疮肾炎肾脏组织中的表达,探讨其在SLE疾病中的临床意义.方法 酶联免疫吸附试验(ELISA)法检测54例SLE患者及27名健康对照组血清FSTL1水平.免疫组织化学染色检测狼疮肾炎患者肾脏组织及健康者肾脏组织中FSTL1的表达情况.采用Mann-WhitneyU/检验、t检验、X2检验及Pearson检验进行统计分析.结果 SLE组FSTL1血清水平(26±21) μg/L显著高于健康对照组(12±14) μg/L(P＜0.01);SLE高血压组明显高于非高血压组(P＜0.01);SLE病程≥5年组与病程＜5年组之间差异有统计学意义(P＜0.01);血清FSTL1表达水平与SLE疾病活动指数(SLEDAI)评分(r=0.319,P=0.022)、年龄(r=0.700,P＜0.01)、病程(r=0.513,P＜0.01)、补体C4 (r=0.443,P=0.004)、总胆固醇(r=0.460,P=0.001)呈正相关;与血小板计数(r=-0.422,P=0.001)、抗双链DNA(dsDNA)抗体水平(r=--0.276,P=0.046)呈负相关.FSTL1主要表达在肾小管上皮细胞胞质内.结论 FSTL1在SLE患者血清中明显升高,且与疾病活动性有关.提示FSTL1在SLE发病机制中起一定作用.     

Pathophysiological significance and clinical utility of circulating osteoprotegerin

Osteoprotegerin (OPG) belongs to the tumor necrosis factor receptor superfamily and acts as a decoy receptor for the receptor activator of NF-kappaB ligand (RANKL), preventing its binding to RANK. Since 1997, the RANKL/RANK/OPG system has been intensively investigated in the fields of bone, immune and cardiovascular system pathophysiology. Specific anti-OPG antibodies have been developed, allowing for the measurement of OPG and, more recently, of soluble RANKL in both physiological and pathological conditions, often yielding unexpected results. When considering circulating OPG measurements, it should be borne in mind that this receptor is ubiquitously expressed, and that circulating levels do reflect the production by a number of tissues. Moreover, strikingly different values of circulating OPG have been reported. The aim of this paper is to summarize the available data on circulating OPG levels in a number of conditions; the pathophysiological significance and potential clinical utility will be emphasized.     

胰岛素对血管内皮细胞中miRNA-21表达和分泌影响的研究

目的探讨胰岛素对血管内皮细胞中miRNA-21的表达和分泌影响。方法用不同浓度胰岛素(0、1、10、50、100和1000nmol/L)干预人脐静脉内皮细胞(HUVECs),48h后收集细胞上清液及细胞,用实时荧光定量PCR方法检测细胞及上清液中miRNA-21的表达情况。结果与0nmol/L胰岛素组相比,10、50、100和1000nmol/L胰岛素组HUVECs中miRNA-21表达均下调(P均<0.05),1000nmol/L胰岛素组细胞中miRNA-21表达最低(P<0.05),但1与0nmol/L胰岛素组HUVECs中miRNA-21表达差异无统计学意义(P>0.05)。与0nmol/L胰岛素组相比,1和10nmol/L胰岛素组HUVECs上清液中miRNA-21表达升高(P<0.05),而50、100和1000nmol/L胰岛素组上清液中miR-NA-21表达降低(P均<0.05),50nmol/L胰岛素组上清液中miRNA-21表达含量最低(P<0.05)。结论不同浓度胰岛素可影响HUVECs中miRNA-21表达,这种变化反映了不同浓度胰岛素对HU-VECs的凋亡和增殖影响。     

Expression of microRNA-502 in gastric cancer tissues and its clinical significance

<正>Objective To explore the expression of microRNA-502 (miRNA-502) and its correlation with clinicopathological features of gastric cancer. Methods A total of 28gastric cancer patients were enrolled in the study. Quantitative real time polymerase chain reaction (qRT-PCR)was used to detect the expression of miRNA-502 in cancer tissues and its paired-adjacent normal tissues.     

The significance of CD44 expression in gastrointestinal neuroendocrine tumors

BACKGROUND/AIMS: Expression of CD44 and its isoforms has been demonstrated to be a prognostic marker in many neoplasms. Gastrointestinal neuroendocrine tumor is a slow-growing neoplasm, whose behavior is determined by site of occurrence, size or specific histologic growth pattern. In this study, the feasibility of using CD44 as a prognostic marker in gastrointestinal neuroendocrine tumor is evaluated. METHODOLOGY: Representative paraffin-embedded sections of gastrointestinal neuroendocrine tumor from 22 patients were studied by immunohistochemical staining using monoclonal antibodies against CD44, Ki-67, and p53 retrospectively. The correlation between these markers and clinical behavior of the tumors was analyzed. RESULTS: Positive expression of CD44 was observed in 15 cases (68%) of gastrointestinal neuroendocrine tumor. Expression of CD44 showed significant inverse correlation with lymph node status (P=0.049), distant metastasis (p<0.001) and mortality (p=0.002). Neither p53 nor Ki-67 correlated with lymph node status, distant metastasis and overall survival. Both lymph node status and distant metastasis showed strong correlation to survival after multivariate analysis. Patients with the tumor growing from the hindgut had better survival (p=0.024). The patients with stronger CD44 immunoreactivity (> or = 2+) tumors had significantly favorable survival (p=0.004) compared with those with weaker immunoreactivity (< or = 1+) tumors. CONCLUSIONS: Expression of CD44 in gastrointestinal neuroendocrine tumor inversely correlates with tumor metastasis, associates with a favorable outcome and may serve as one of the prognostic indicators.     

Changes of microRNA-1 and microRNA-21 in human atrial fibrillation

Objectives To investigate changes of microRNA- 1(miR-1) and microRNA-21(miR-21) expressions in human atrial fibrillation(AF).Methods Right atrial appendages were obtained from 12 rheumatic valvular heart disease patients with sinus rhythm(SR)and 14 patients with chronic AF.Quantitative real time polymerase chain reaction(qRT-PCR) was applied to assess expressions of miR-1 and miR- 21.Immunohistochemistry was used to evaluate Kir2.1 expression and masson staining was used to estimate collagen deposition.Results Expressions of miR-1 was decreased (relative expression:0.68±0.09 vs.1.76±0.15,PmiR-21 was increased(relative expression:2.23±0.31 vs.0.94±0.24 vs. 0.043±0.005 vs.8.3±0.01;PmiR-l was negatively correlated to that of left atrium diameters(r=-0.47,P=0.02).Expression of miR-21 was positively correlated to collagen content (r=0.45,P<0.01).Conclusions Expression of miR-1 was down-regulated in AF patients,which may be associated with the increase in Kir2.1.miR-21 level was significantly up-regulated, which may contribute to the increase in collagen content in the atrium.     

多效生长因子在消化系肿瘤中的表达及意义

多效生长因子(pleiotrophin,PTN)是分泌性肝素结合细胞因子,PTN基因作为一个原癌基因,与肿瘤的发生和发展关系密切。PTN可分泌到细胞外液(包括血液)中,与肝素具有高亲和性。PTN在细胞分裂、血管生成、神经系统发育和神经系统损伤性疾病以及肿瘤等方面均有作用。近年来研究表明PTN在肿瘤的发生和发展中起着重要的作用,PTN高表达于大多数肿瘤中,尤其是消化系统肿瘤,其表达水平可以作为肿瘤诊断、治疗、预后评价的指标。本文结合国内外文献对PTN在消化系统肿瘤的表达水平及其意义作一概述。     

Measurement of serum circulating intercellular adhesion molecule-1 and its clinical significance in hepatocellular carcinoma: preliminary report

Serum circulating intercellular adhesion molecule-1 (cICAM-1) was measured in 50 patients with hepatocellular carcinoma (HCC). The mean cICAM-1 level in the 50 patients was 2220 ng/ml and 43 patients (86%) had a high level of cICAM-1 — more than 1000 ng/ml. Comparative analysis of cICAM-1 and alpha-fetoprotein (AFP) levels in the HCC patients showed that serum AFP level was negative (<20 ng/ml) in five patients or “questionable positive” (20—90 ng/ml) in ten patients, while the levels of cICAM-1 in these patients were 1810 and 1710 ng/ml, respectively. Seven patients who underwent hepatectomy had tumor recurrences during a follow-up period of 6—18 months. Their serum AFP levels were lower than 200 ng/ml (mean value, 27 ng/ml), but their mean cICAM-1 level was 1956 ng/ml at the time tumor recurrence was diagnosed. We suggest that the measurement of serum cICAM-1 is not only useful for prediction of the progression and prognosis of HCC, but that it may also be an important marker for the early diagnosis of the disease, and for monitoring postoperative recurrence, particularly in patients with low levels of serum AFP.