MicroRNA-139 is a predictor of prostate cancer recurrence and inhibits growth and migration of prostate cancer cells through cell cycle arrest and targeting IGF1R and AXL

Background: We previously identified a panel of five microRNAs (miRNAs) associated with biochemical recurrence and metastasis following prostatectomy from prostate cancer patients using next-generation sequencing-based whole miRNome sequencing and quantitative polymerase chain reaction-based validation analysis. In this study, we examined the mechanism of action of miR-139-5p, one of the downregulated miRNAs identified in the panel. Methods: Using a cohort of 585 patients treated with radical prostatectomy, we examined the prognostic significance of miR-139 (dichotomized around the median) using the Kaplan-Meier method and Cox proportional hazard models. We validated these results using The Cancer Genome Atlas (TCGA) data. We created cell lines that overexpressed miR-139 to confirm its targets as well as examine pathways through which miR-139 may function using cell-based assays. Results: Low miR-139 expression was significantly associated with a variety of prognostic factors in prostate cancer, including Gleason score, pathologic stage, margin positivity, and lymph node status. MiR-139 expression was associated with prognosis: the cumulative incidence of biochemical recurrence and metastasis were significantly lower among patients with high miR-139 expression (P = .0004 and .038, respectively). Validation in the TCGA data set showed a significant association between dichotomized miR-139 expression and biochemical recurrence (odds ratio, 0.52; 95% confidence interval, 0.33-0.82). Overexpression of miR-139 in prostate cancer cells led to a significant reduction in cell proliferation and migration compared with control cells, with cells arrested in G2 of cell cycle. IGF1R and AXL were identified as potential targets of miR-139 based on multiple miRNA-binding sites in 3′-untranslated regions of both the genes and their association with prostate cancer growth pathways. Luciferase assays verified AXL and IGF1R as direct targets of miR-139. Furthermore, immunoblotting of prostate cancer cells demonstrated IGF1R and AXL protein expression were inhibited by miR-139 treatment, which was reversed by the addition of miR-139 antagomir. Examination of the molecular mechanism of growth inhibition by miR-139 revealed the downregulation of activated AKT and cyclin D1, with upregulation of the CDK inhibitor p21. Conclusions: miR-139 is associated with improved prognosis in patients with localized prostate cancer, which may be mediated through downregulation of IGF1R and/or AXL and associated signaling pathway components.     

miR-214和miR-181c在胃癌组织中的表达及预后价值

目的探讨微小RNA-214（miR-214）和miR-181c在胃癌组织中的表达水平及对预后的影响。 方法选取2014年1月至2015年1月于川北医学院附属医院收治的68例胃癌患者为研究对象,均接受手术治疗,出院后随访1~60个月。利用实时荧光定量PCR技术检测患者癌组织和癌旁组织miR-214、miR-181c相对表达量;利用Kaplan-Meier曲线进行生存分析;Cox多因素回归分析影响胃癌患者预后的独立危险因素。 结果胃癌组织中miR-214、miR-181c表达水平均明显低于癌旁组织,差异有统计学意义（P<0.05）。根据miR-214、miR-181c表达均值将患者分为高表达组和低表达组,miR-214、miR-181c表达水平与年龄、性别、淋巴结是否转移无关,与TNM分期、肿瘤分化程度有关（P<0.05）。患者总生存率为44.12%,miR-214低表达组和高表达组术后5年累积生存率分别为35.71%、57.69%,两组间比较差异有统计学意义（P=0.035）;miR-181c低表达组和高表达组术后5年累积生存率分别为35.55%、60.87%,差异有统计学意义（P=0.024）。Cox多因素回归分析结果显示,TNM分期高（HR=1.569,95% CI：1.029~2.391,P=0.036）、miR-214低表达（HR=1.643,95% CI：1.294~2.087,P<0.001）及miR-181c低表达（HR=1.327,95% CI：1.045~1.685,P=0.021）是影响胃癌患者预后的独立危险因素。 结论miR-214、miR-181c在胃癌组织中表达显著下调,与胃癌患者临床病理参数及不良预后有关,参与胃癌的发生发展过程。     

Prostate cancer risk and aggressiveness associated with the CYP1B1 4326C/G (Leu432Val) polymorphism: a meta-analysis of 2788 cases and 2968 controls

To derive a precise estimation of the associations between the cytochrome P450 1B1 (CYP1B1) 4326C/G variants and prostate cancer (PCa) risk or aggressiveness, a meta-analysis was performed using all eligible published studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association in seven literature studies with 2788 cases and 2968 controls. In the overall analysis, no significant association was found between the CYP1B1 4326C/G polymorphism and PCa risk, but ethnicity subgroup analyses and a case-source analysis revealed significant associations. The 4326G allele showed a significant association with increased PCa risk in Asians (OR=1.52, 95% CI: 1.20–1.92), and significant associations were also observed in a heterozygote comparison (OR=1.40, 95% CI: 1.03–1.89), a homozygote comparison (OR=2.38, 95% CI: 1.31–4.33) and in a dominant genetic model (OR=1.52, 95% CI: 1.14–2.01). Moreover, the 4326G allele was also significantly correlated with an increased risk of sporadic PCa (OR=1.13, 95% CI: 1.04–1.24), and significant associations were observed in a heterozygote comparison (OR=1.16, 95% CI: 1.02–1.33), a homozygote comparison (OR=1.24, 95% CI: 1.03–1.49) and a dominant genetic model (OR=1.19, 95% CI: 1.05–1.34). The overall analyses and all subgroup analyses showed no significant association between the 4326C/G polymorphism and PCa aggressiveness. Our meta-analysis showed that CYP1B1 4326G allele is significantly associated with an increased PCa risk in Asians and in sporadic PCa cases.     

Effect of obesity on the prognosis and recurrence of prostate cancer after radical prostatectomy: a meta-analysis

BackgroundObesity has been found to be closely related to the increased risk of fatal prostate cancer (PCa), however there remains no evidence that further clarifies the relationship between obesity and the postoperative recurrence and poor prognosis of PCa. In this study, a systematic review and meta-analysis were performed to systematically evaluate the effect of obesity on the prognosis and recurrence of PCa after radical prostatectomy (RP).MethodsA literature search of the PubMed, Web of Science, and Embase databases was performed covering articles published between January 2013 and January 2020. Articles regarding the correlation between body mass index (BMI) and the prognosis and recurrence of PCa following RP were included in the meta-analysis. Two investigators independently screened the literature and extracted relevant data including publication information, key results, number of cancer cases, and multivariable-adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Meta-analysis was performed using RevMan 5.3 and Stata 16.0 software, and forest plots, funnel plots, and sensitivity analysis were also conducted.ResultsA total of 14 articles were included, all of which were analyzed for clinicopathological characteristics. Eight articles reported the biochemical recurrence (BCR) with prostate-specific antigen (PSA) as the predictor, and six articles reported the positive surgical margins (PSM). The meta-analysis showed that obese PCa patients had more postoperative recurrence and poor prognosis compared with the normal weight PCa patients, and the difference was statistically significant (OR =1.25, 95% CI: 1.10, 1.43). BCR exhibited no significant difference between obese and non-obese PCa patients after surgery (OR =1.2, 95% CI: 0.96, 1.46), and there were also no notable differences in PSM between the groups (OR =1.16, 95% CI: 0.99, 1.36). Subgroup analysis showed that obese PCa patients in the Americas (95% CI: 1.11, 1.37) and Europe (95% CI: 1.11, 1.78) were more likely to have surgical recurrence and poor prognosis (OR =1.40). Obese patients in the Americas were also more likely to have BCR after surgery (95% CI: 1.07, 1.36).ConclusionsObesity easily leads to poor prognosis and recurrence of PCa after RP.     

术前血清miR-20a、miR-17在结直肠癌预后评估中的价值

目的探讨结直肠癌患者术前血清miR-20a、miR-17水平在术后不良临床结局评估中的价值。 方法选择2013年8月至2016年2月华中科技大学同济医学院附属协和医院就诊的结直肠癌患者73例作为病例组,收集患者术前以及术后1周、1个月、3个月时的血清标本,另收集81名同期体检健康对照组的血清标本,采用实时荧光定量PCR法检测两组血清miR-20a、miR-17表达水平。根据表达平均数分为高表达组与低表达组,采用Kaplan-Meier法对两组进行生存分析;Cox比例风险回归模型筛选不良预后的影响因素,受试者工作特征（ROC）曲线分析血清miR-20a、miR-17水平对结直肠癌不良预后的诊断效能。 结果病例组患者术后血清miR-20a、miR-17水平呈下降趋势（P<0.05）,且各检测点水平均高于对照组（P<0.05）。分化程度（HR=1.462,95% CI：1.096~1.951）、TNM分期（HR=1.642,95% CI：1.339~2.014）、术前血清miR-20a（HR=1.575,95% CI：2.035~3.652）、miR-17水平（HR=2.491,95% CI：2.131~2.914）是影响结直肠癌患者不良预后的独立危险因素（均P<0.001）。术前血清miR-20a、miR-17高表达者的3年总生存率更低（22.0% vs 78.3%,21.3% vs 73.1%,P<0.05）;两者联合检测预测结直肠癌患者预后不良的曲线下面积为0.955,敏感度为97.6%,特异度为91.2%。 结论结肠癌患者术前血清miR-20a、miR-17高表达与患者不良预后有关,术前检测有助于改善不良预后高风险患者的临床结局。     

The risks,degree of malignancy and clinical progression of prostate cancer associated with the MDM2 T309G polymorphism: a meta-analysis

To determine the risk, malignant degree and clinical progression of prostate cancer (PCa) associated with mouse double-minute 2 protein (MDM2) T309G variants, a meta-analysis was performed on all eligible published studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess these associations in seven studies that included 5151 cases and 1003 controls. In the overall analysis, the 309G allele was significantly associated with a decreased PCa risk (OR=0.85, 95% CI: 0.74–0.97); this was also the case for the homozygous comparison (OR=0.72, 95% CI: 0.55–0.95) and the dominant genetic model (OR=0.79, 95% CI: 0.65–0.96). The 309G allele was also found to be significantly associated with lower degrees of PCa malignancy (OR=0.85, 95% CI: 0.75–0.96) in the overall analysis, as well as in the heterozygous comparison (OR=0.79, 95% CI: 0.65–0.96), homozygous comparison (OR=0.76, 95% CI: 0.58–0.98) and dominant genetic model (OR=0.81, 95% CI: 0.68–0.96). Furthermore, grouping analysis showed that the 309G allele in Caucasians was significantly correlated with a decreased PCa risk (OR=0.77, 95% CI: 0.61–0.96); this was also the case in the homozygous comparison (OR=0.51, 95% CI: 0.31–0.86). The grouping analysis also showed that the 309G variant in Caucasians was significantly associated with a lower degree of PCa malignancy in all of the genetic models. In addition, we found that the 309G variant in Caucasians was significantly associated with a slower PCa clinical progression in all of the genetic models. In summary, our meta-analysis showed that the MDM2 309G variant was significantly associated with a decreased PCa risk, lower malignant degree and slower clinical progression in Caucasians, but there was no obvious association in the Asian population.     

Do androgen-directed therapies improve outcomes in prostate cancer patients undergoing radical prostatectomy? A systematic review and meta-analysis

IntroductionApproximately 50% of patients with non-metastatic prostate cancer are treated with radical prostatectomy (RP). While some men will be cured with surgery alone, a substantial proportion will experience cancer recurrence. Androgen-directed therapy (ADT) is an effective adjuvant therapy for patients treated with prostate radiation. Comparatively, the efficacy of ADT in surgical patients has not been well-studied.MethodsA systematic search of MEDLINE, Embase, and the Cochrane Library from inception to July 2020 was performed. Randomized trials comparing ADT with RP vs. prostatectomy alone in patients with clinically localized prostate cancer were included. Neoadjuvant ADT and adjuvant ADT interventions were assessed separately. The primary outcomes were cancer recurrence-free survival (RFS) and overall survival (OS). Pathological outcomes following neoadjuvant ADT were also evaluated.ResultsFifteen randomized trials met eligibility criteria; 11 evaluated neoadjuvant ADT (n=2322) and four evaluated adjuvant ADT (n=5205). Neoadjuvant ADT (three months of treatment) did not improve RFS (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.74–1.11) or OS (HR 1.22, 95% CI 0.62–2.41). Neoadjuvant ADT significantly decreased the risk of positive surgical margins (relative risk [RR] 0.48, 95% CI 0.41–0.56) and extraprostatic tumor extension (RR 0.75, 95% CI 0.64–0.89). Adjuvant ADT improved RFS (HR 0.65, 95% CI 0.45–0.93) but did not improve OS (HR 1.02, 95% CI 0.84–1.24).ConclusionsNeoadjuvant ADT causes a pathological downstaging of prostate tumors but has not been found to delay cancer recurrence nor extend survival. Few studies have evaluated adjuvant ADT. Trials are needed to determine the benefits and harms of intermediate- or long-term adjuvant ADT for RP patients.     

Genetic polymorphisms in HIF1A are associated with prostate cancer risk in a Chinese population

The hypoxia-inducible factor-1α (HIF-1α) plays an important role in regulating angiogenesis, which is essential for tumor growth and metastasis. Genetic variations of HIF1A (coding HIF-1α) have been shown to influence an individual''s susceptibility to many human tumors; however, evidence on associations between HIF1A single-nucleotide polymorphisms (SNPs) and prostate cancer (PCa) risk is conflicting. We genotyped three potentially functional polymorphisms in HIF1A (rs11549465, rs11549467 and rs2057482) using the TaqMan method and assessed their associations with PCa risk in a case–control study of 662 PCa patients and 716 controls in a Chinese Han population. Compared with rs11549467 GG genotype, the variant genotypes GA+AA had a significantly increased PCa risk (adjusted odds ratio (OR)=1.70; 95% confidence interval (CI)=1.06–2.72), particularly among older patients (OR=2.01; 95%CI=1.05–3.86), smokers (OR=2.06; 95%CI=1.07–3.99), never drinkers (OR=2.16; 95%CI=1.20–3.86) and patients without a family history of cancer (OR=1.71; 95%CI=1.02–2.89). Furthermore, patients with rs11549467 variant genotypes were associated with a higher Gleason score (OR=2.14; 95%CI=1.22–3.75). No altered PCa risk was associated with the rs11549465 and rs2057482 polymorphism. However, the combined variant genotypes of rs2057482 and rs11549467 were associated with increased PCa risk (OR=2.10; 95%CI=1.23–3.57 among subjects carrying three or more risk alleles). These results suggest that HIF1A polymorphisms may impact PCa susceptibility and progression in the Chinese Han population.     

粪便miRNAs在胰腺导管腺癌筛查诊断中的应用价值

目的 检测胰腺导管腺癌（pancreatic ductal adenocarcinoma,PDAC）患者癌组织、配对癌旁组织及粪便miRNAs,评价粪便miRNAs筛查诊断PDAC的价值.方法 收集30例PDAC患者癌组织、癌旁组织及其粪便标本,10例慢性胰腺炎（CP）患者及15例健康志愿者粪便标本,抽提组织及粪便miRNAs,应用实时定量PCR法检测各组样本miR-21、miR-155、miR-196a、miR-216及miR-217的表达量.应用受试者工作曲线（receiver operating characteristic curve,ROC）及其曲线下面积（AUC）评估粪便miRNAs对PDAC的诊断价值.结果 目的miRNAs在癌组织、癌旁组织及粪便标本中均可被检测.粪便miRNAs抽提及检测方法具有可重复性.MiR-21、miR-155、miR-196a在PDAC组织中表达水平高于癌旁组织,而miR-216、miR-217在PDAC组织中表达水平低于癌旁组织（P＜0.01）.与慢性胰腺炎及健康对照组相比,PDAC患者粪便中miR-21及miR-155的相对表达水平都增加,miR-216的相对表达水平降低（P＜0.05）.PDAC组与对照组相比,miR-21、miR-155及miR-216两两组合后的AUC均比单个miRNA的AUC高,而三者联合后的AUC在所有组合中最高达到0.8667（95％CI：0.7722-0.9612）,诊断胰腺癌的敏感性和特异性分别为83.33％和83.33％,两组比较差异有统计学意义（P＜0.0001）.结论 粪便miRNAs的抽提和检测具有可重复性.粪便中miR-21、miR-155和miR-216有可能成为PDAC诊断的潜在分子标记物.     

肿瘤组织microRNA-21高表达增加淋巴结转移的荟萃分析

目的: 分析不同肿瘤组织中microRNA-21（miR-21）的异常表达及其与淋巴结转移的相关性。方法: 检索PubMed、Web of Science 、EMbase、CBM数据库,截至2017年10月。采用随机效应模型,计算肿瘤组织miR-21表达高、低两组淋巴结转移的OR、95%CI。同时,本研究也运用异质性检验、敏感性分析和出版偏移等统计学分析。结果: 最终纳入16篇文献共1 492例。miR-21表达水平较高组（OR=2.01, 95%CI=1.36~2.97, P<0.001）明显增加淋巴结转移。亚组分析结果表明,miR-21高表达组在消化系统肿瘤（OR=2.22,95%CI=1.49~3.30）,膀胱和宫颈癌（OR=5.48,95%CI=1.84~16.30）中明显增加淋巴结转移风险,其中也发现病人样本数<60例,OR=2.39, 95%CI=1.44~3.98, P<0.001;≥60例,OR=1.78, 95%CI=1.04~3.05, P=0.036。乳腺癌、喉和肺癌的miR-21表达,未发现与淋巴结转移的关系。结论: 本研究发现,肿瘤组织miR-21高表达组明显增加淋巴结转移的风险。亚组分析结果表明,miR-21在消化系统肿瘤以及膀胱和宫颈癌中,可作为淋巴结转移的标志物。     

Long-term cancer control after radical prostatectomy and bilateral pelvic lymph node dissection for pT3bN0M0 prostate cancer in the prostate-specific antigen era

ObjectivesWe evaluated long-term cancer control outcomes of radical prostatectomy and bilateral pelvic lymph node dissection (RP) for pT3bN0M0 prostate cancer in the era of prostate-specific antigen (PSA) screening.Materials and methodsA retrospective analysis of prospectively collected data from the University of Southern California Prostate Cancer Database was performed. Between 1987 and 2008, 229 men underwent open RP for pT3bN0M0 prostate cancer. The cohort was divided into early (1987–1997) and contemporary (1998–2008) PSA eras. The Kaplan-Meier method and Cox proportional regression models were used to analyze clinical recurrence (CR) and biochemical recurrence (BCR).ResultsThe median follow-up duration was 14.5 years (range, 0.2–21.1 y). The predicted 10-year freedom from CR and BCR rates for men treated in the early and contemporary PSA eras were 73% and 95% (Log-rank P = 0.001) and 65% and 73% (Log-rank P = 0.055), respectively. Multivariable analysis showed that pathologic Gleason grade 8–10 (CR: hazard ratio [HR] = 5.11; 95% confidence interval [CI] = 1.72–15.20; P = 0.003; BCR: HR = 3.47; 95% CI = 1.60–7.48; P = 0.002) and contemporary PSA era (CR: HR = 0.15; 95% CI = 0.06–0.41; P<0.001; BCR: HR = 0.49; 95% CI = 0.28–0.86; P = 0.013) were independently associated with cancer control. Adjuvant radiation therapy and positive surgical margins were not independently associated with outcomes.ConclusionsRP conferred long-term cancer control in men with pT3bN0M0 prostate cancer treated in the PSA era. Pathologic Gleason grade 8–10 and treatment in the early PSA era were independently associated with poorer cancer control outcomes.     

乳腺癌组织中 miR-21的表达及意义

目的 对乳腺癌组织及其相应癌旁组织中miR-21进行定量检测,分析其表达与临床病理特征的及意义.方法 采用茎环实时荧光逆转录聚合酶链反应(RT-PCR)检测60例乳腺癌及其对应癌旁组织中miR-21的表达量,分析其表达与肿瘤大小、TNM分期、组织学类型、淋巴结转移、雌激素受体(ER)、孕激素受体(PR)等临床病理特征的关系.结果 实时RT-PCR方法 检测miR-21表达的敏感性和特异性良好.miR-21在乳腺癌组织中的表达明显高于癌旁组织(P＜0.001);miR-21的高表达还与较高的TNM分期,淋巴结转移及PR的表达程度有关(各分组间P＜0.01及＜0.05);miR-21的表达在"三阴性乳腺癌"(ER,PR,CerbB-2均为阴性)和"非三阴性乳腺癌"之间的表达存在统计学差异(P=0.029).结论 miR-21在乳腺癌组织中高表达,其水平可能与乳腺癌的恶性程度有关.     

The effect of obesity on pathological complete response and survival in breast cancer patients receiving uncapped doses of neoadjuvant anthracycline-taxane-based chemotherapy

PurposeThe effect of obesity in breast cancer patients undergoing neoadjuvant chemotherapy (NAC) remains controversial. The aim of this study was to determine the obesity-related effect on pathological complete response (pCR) and survival in women receiving full uncapped doses of NAC.MethodsWe retrospectively analyzed the data of all consecutive women who underwent anthracycline-taxane-based NAC for primary breast cancer between 2005 and 2015 at the Department of Obstetrics and Gynecology, Medical University of Vienna. Following the WHO criteria, women with a body mass index (BMI) ≥30 kg/m² at baseline were considered obese, whereas those with a BMI <30 kg/m² were considered non-obese. Those with dose reductions or dose capping were not eligible for study inclusion. Cox regression and logistic regression were performed. The Kaplan-Meier method was used to analyze disease-free, progression-free, and overall survival. The pCR served as the main outcome measure.ResultsAmong 120 women who received neoadjuvant epirubicin plus cyclophosphamide and docetaxel, 28 (23.3%) were obese and 92 (76.7%) were non-obese. In the multivariate logistic regression model that adjusted for potentially confounding variables, obesity had an independent positive predictive effect on pCR (OR 4.29, 95% CI, 1.42–13.91; p = 0.011), which was significant in the postmenopausal subgroup (OR 4.72, 95% CI, 1.47–15.84; p = 0.01). When comparing non-obese with obese women, we found that obese women experienced longer progression-free survival (HR 0.10, 95% CI, 8.448 × 10⁻⁴–0.81; p = 0.025).ConclusionsObese women receiving full uncapped doses of anthracycline-taxane-based NAC have increased pCR and favorable progression-free survival. This could result from increased dose intensity with increased efficacy and toxicity.     

循环miR-21对胰腺癌诊断价值的Meta分析

目的:通过Meta分析系统评价血液中miR-21对胰腺癌的诊断价值。方法:检索多个国内外数据库,收集2017年5月以前公开发表的关于miR-21用于胰腺癌诊断的研究数据,按照纳入标准筛选文献、提取资料和质量评价,然后采用Metadisc 1.4和Stata 14.0软件对纳入研究进行Meta分析。结果:共纳入8篇文献,累计261例胰腺癌患者和242例对照。Meta分析结果显示,循环miR-21诊断胰腺癌的合并敏感度为0.76(95%CI=0.71~0.81),合并特异度为0.76(95%CI=0.70~0.81),合并阳性似然比为3.17(95%CI=2.24~4.47),合并阴性似然比为0.26(95%CI=0.15~0.45),合并诊断比值比为13.17(95%CI=6.78~25.58)。综合受试者工作特征曲线下面积(AUC)为0.8518。亚组分析显示,血清和血浆亚组的AUC均为0.8513;健康人群对照亚组的诊断准确性优于健康人群+胰腺良性疾患对照亚组(AUC:0.876 vs.0.72,P0.05)。诊断性试验Deek漏斗图显示不存在发表偏倚,敏感性分析显示Meta分析结果并未过分依赖于某个研究,结论稳定。结论:循环miR-21用于胰腺癌诊断具有一定的价值。     

Diagnostic significance of miR‐21, miR‐141, miR‐18a and miR‐221 as novel biomarkers in prostate cancer among Egyptian patients

Prostate cancer (PC) is considered as the fifth cause of cancer deaths worldwide. The exact etiopathogenesis is unclear; however, genetic predisposition, hormonal influencers, lifestyle and environmental factors act as major contributors. It has been found that several miRNAs may play a crucial role in cancer initiation and progression. Here, in this study, we evaluated the peripheral blood levels of miR‐21, miR‐141, miR‐221 and miR‐18a expression among 80 prostate cancer patients (50 localised and 30 metastatic) and 30 benign prostatic hyperplasia patients compared to 50 normal control subjects, using RT‐PCR. Our results of analysis of miR‐21, miR‐141, miR‐18a and miR‐221 in the plasma of PC patients showed that miR‐18a is a powerful discriminator of PC patients from healthy controls as it had the highest AUC (0.966; 95% CI, 0.937–1.000), while miR‐221 provided better differentiation of metastatic from localised PC (sensitivity was 92.9% at 100% specificity), and when we combine miR‐18a and miR‐221 for differentiating patients with MPC, it will increase the sensitivity to 96.4% at a specificity of 100% (AUC, 0.997; 95% CI, 0.988–1.0) (p < .000). This current study recommends that analysis of these miRNAs might have clinical value in enhancing PSA testing.     

miR-21 inhibition reverses doxorubicin-resistance and inhibits PC3 human prostate cancer cells proliferation

Many approaches have been examined to reversing multidrug resistance (MDR), but sub-optimal target-based strategies have limited their efficacy. Herein, we investigate microRNA (miR-21) suppression on the doxorubicin (DOX)-sensitisation of the DOX-resistant (PC3/DOX) cell line in prostate cancer (PCa). Expression levels of miR-21, P-glycoprotein (P-gp), MDR-1 and PTEN evaluated in PC3/DOX cancer cells by qRT-PCR and western blot analyses. The cytotoxic effects of transfected of miR-21 were assessed by MTT assay for 72 hr. Rhodamine123 (Rh123) assay was employed to define the activity of P-gp. Apoptosis was detected by Flow cytometry. As expected, miR-21 was expressed highly in PC3/DOX cells (p < 0.05). It was shown that miRNA‑21 suppression considerably hindered PC3/DOX cell viability. miR‑21 suppression dramatically downregulated P-gp expression and activity in DOX-resistance cells and abolished MDR by an increment of intracellular accumulation of DOX in PC3/DOX cells (p < 0.05). PTEN is a key modulator of the PI3K/Akt/P-gp cascade, which miR-21 suppression led to the upregulation of PTEN and sequentially lower-expression of P-gp that reversed MDR. Also, miR-21 repression enhanced the apoptosis rate of PC3/DOX cells. The findings of this paper contribute to the current understanding of the functions of miR-21 in MDR-reversing in PCa.     

术中腹腔内植入氟尿嘧啶对结直肠癌患者免疫功能及miR-34a、ZEB2表达的影响

目的探讨术中腹腔内植入氟尿嘧啶（5-Fu）对结直肠癌患者免疫功能及miR-34a、ZEB2表达的改变以及生存影响。 方法选择2014年1月至2016年12月在延安大学咸阳医院接受根治性手术治疗的结直肠癌患者92例,采用随机数字表法分为2组,各46例。对照组患者行腹腔镜下结直肠癌根治性切除术,观察组在关腹前给予5-Fu植入剂,术后两组均给予营养支持及预防性使用抗生素。对比两组患者1年生存率、复发率、免疫功能及miR-34a、ZEB2血清表达情况。 结果（1）两组术后住院时间差异无统计学意义（t=0.251、P=0.401）。观察组无病生存时间为（10.26±1.29）个月,显著长于对照组的（8.92±1.02）个月,差异有统计学意义（t=-5.526,P<0.01）。对照组1年生存率为78.26%（95% CI=72.13%~84.39%）,观察组1年生存率为95.65%（95% CI=93.91%~97.39%）,两组比较,差异有统计学意义（χ²=5.896,P=0.015）。（2）治疗后两组各免疫指标均呈明显下降后升高的趋势（P<0.05）,术后2 d时观察组IgM明显高于对照组（P<0.05）,术后7 d时观察组IgA与CD4⁺明显低于对照组（P<0.05）。（3）治疗前两组血清miR-34a及ZEB2蛋白表达水平比较,差异无统计学意义（t=-1.097、1.392,P=0.259、0.138）。治疗后7 d时,观察组和对照组miR-34a蛋白表达均明显升高（t=3.975、-3.718,P=0.001、0.005）,ZEB2蛋白表达明显下降（t=6.279、4.183,均P<0.001）,但观察组miR-34a及ZEB2蛋白表达水平的变化幅度较对照组更为明显（t=-2.813、4.118,P=0.029、<0.001）。 结论结直肠癌患者术中腹腔内植入5-Fu对患者1年生存率及复发率均无明显影响,但对患者免疫功能有一定抑制作用,可改善miR-34a低表达,抑制ZEB2高表达。