转录因子FOXO1在前列腺癌组织中的表达及临床意义

目的:检测前列腺癌(PCa)组织与良性前列腺增生(BPH)组织中转录因子FOXO1的表达情况,探讨FOXO1与PCa临床病理参数之间的关系。方法:收集2010年1月～2016年12月我院53例PCa患者行根治性前列腺切除术后病理标本和经尿道前列腺电切术的53例BPH病理标本,采用组织芯片方式收集组织标本,使用免疫组化染色法检测FOXO1表达情况,分析FOXO1表达同PCa患者临床病理参数之间的关系。结果:BPH组织中FOXO1呈高表达,PCa组织中FOXO1表达显著低于BPH组织(39.6%vs.86.8%,P0.05),中低危PCa组织的相对表达量显著高于高危PCa组织(P0.05)。FOXO1表达与PCa PSA水平、病理T分期、淋巴结转移、Gleason评分显著相关(P0.05),Gleason评分越高FOXO1水平越低,PCa组织中FOXO1表达与患者年龄、前列腺体积、切缘阳性无明显相关性(P0.05)。结论:FOXO1在PCa组织中异常低表达,与PCa侵袭转移相关,FOXO1表达与PCa PSA水平、病理T分期、淋巴结转移和Gleason评分密切相关。     

FOXA1通过调控XBP1的转录促进乳腺癌增殖的功能及机制研究

目的 探究先锋转录因子FOXA1在乳腺癌中的功能及其发挥功能的分子机制。方法利用cBioPortal数据库分析FOXA1在肿瘤中的突变情况,利用TCGA数据库分析FOXA1在乳腺癌组织中的mRNA表达水平及其与患者预后的关系;采用CCK-8和克隆集落形成实验探究FOXA1和X盒结合蛋白1(XBP1)对ERα阳性乳腺癌细胞增殖能力的影响;采用流式细胞技术分析FOXA1对ERα阳性乳腺癌细胞周期的影响;联合转录组学和GEO数据库分析乳腺癌中受FOXA1调控的基因及信号通路;采用蛋白质印迹技术和RT-qPCR技术验证受FOXA1调控的基因的表达情况。结果 在肿瘤中,FOXA1在多个位点发生突变;FOXA1在乳腺癌组织中的表达水平显著高于正常组织,并且FOXA1的高表达与患者的不良预后呈正相关;相比于其他乳腺癌分型,FOXA1在Luminal型乳腺癌中呈显著高表达;转录组和染色质免疫共沉淀分析一共鉴定到177个受FOXA1直接转录调控的基因,其中包括XBP1;通路富集分析表明,受FOXA1调控的基因显著富集在细胞周期和DNA复制通路上;在ERα阳性乳腺癌细胞系中,沉默FOXA1或者XBP1的表...     

CYP1A2基因多态性与前列腺癌的相关性研究

目的:评价CYP1A2基因单核苷酸多态性(SNPs)与前列腺癌分期分级的相关性。方法:对253例良性前列腺增生(BPH)患者与206例去势前列腺癌患者CYP1A2基因中rs2069514-3859(A>G)位点及rs2069525-1707(C>T)位点进行基因测序,并对各基因表型与前列腺癌的分期分级相关性进行统计学分析。结果:BPH及去势前列腺癌患者的两种CYP1A2单核苷酸多态性的发生率无明显差异(P>0.05),其基因多态性与前列腺癌的病理分期均无相关性(P>0.05);但rs2069525-1707(C>T)中含C等位基因型的前列腺癌Gleason评分多在7分以下(P=0.030,OR=4.658,95%CI:1.222～17.754)。结论:CYP1A2基因的SNPs与前列腺癌的病理分级之间可能有一定的相关性,但其发生机制及临床意义有待进一步证实及研究。     

血清网膜素-1与前列腺癌的相关性研究

目的：研究血清脂肪因子网膜素-1(omentin-1)与前列腺癌的相关性.方法2015年7月至2016年3月我科收治的前列腺癌患者44例作为肿瘤组,同期前列腺增生患者42例作为对照组,两组患者的年龄相匹配,均空腹经肘静脉采集血液,ELISA 法测定血清 omentin-1水平.结果与对照组相比,肿瘤组患者 omentin-1、PSA、高密度脂蛋白胆固醇(HDL-C)水平明显升高,差异有统计学意义(P ＜0．05).各项参数的 Spearman 相关性分析显示 omentin-1与 HDL-C、PSA水平呈正相关(分别 r ＝0．363,P ＝0．0006;r ＝0．356,P ＝0．0008),与空腹血糖水平呈负相关(r ＝－0．230,P ＝0．033).二项 Logistic 回归分析显示 omentin-1水平的独立影响因素是肿瘤分组,即罹患前列腺癌是使患者血清 omentin-1水平升高的一个独立影响因素(P ＝0．0004).结论血清脂肪因子 omentin-1水平在前列腺癌与前列腺增生患者间有显著差异,提示其可能与前列腺癌的发生发展相关.     

转录因子12对前列腺癌进展及预后的影响

目的:探讨转录因子12(TCF12)对前列腺癌进展及预后的影响。方法:利用在线生信分析网站UALCAN、基因表达谱动态分析(GEPIA)、基因、蛋白质相互作用关系检索工具(STRING)及METASCAPE分析TCF12在前列腺组织中表达(高表达组和低表达组)及其与预后的关系,预测TCF12相关基因发挥作用的可能信号通...     

前列腺癌组织中转化性生长因子β1的免疫组织化学研究

应用免疫组化（ＡＢＣ）方法检测２８例前列腺癌和２６例前列腺癌增生组织中转化性生化因子β１（ＴＣＦ－β１）的表达情况，结果表明：ＴＧＦ－β１在前列腺癌和前列腺癌增生的基质染色强度和染色范围相似，而在上皮部分，癌性上皮的染色强度和范围明显高于或大于前列腺增生的腺上皮的染色强度和范围，差异均具有高度显著性意义（Ｐ〈０．０１）。４例正常前列腺仅见基质染色，但强度和染色范围远小于前列腺癌和前列腺增生，结果提     

缺氧诱导因子-1与前列腺癌研究进展

缺氧诱导因子-1(HIF-1)与前列腺癌存在密切的关系。研究表明HIF-1在前列腺癌中不但与血管生成因子、增殖与存活因子、葡萄糖转运以及糖分解酶等有关,而且与p53、p21、信号转导通路等有关。通过对HIF-1的深入研究将对前列腺癌的诊断与治疗提供新的思路。现对HIF-1的结构、功能及与前列腺癌关系进行综述。     

前列腺癌相关新基因PCAG1的筛选和鉴定

目的筛选和鉴定新的前列腺癌相关基因,探讨其在前列腺癌中的表达情况,为研究其在前列腺癌发生、发展中的作用奠定基础。方法通过生物学信息筛选,RT-PCR验证,确定前列腺癌相关新基因PCAG1,然后提取14例配对前列腺癌及癌旁组织标本中总RNA,经逆转录获得cDNA,应用RT-PCR检测标本中PCAG1 mRNA表达水平。免疫组织化学染色检测PCAG1在38例前列腺癌组织及配对邻近正常组织中蛋白表达水平,免疫荧光法确定PCAG1蛋白亚细胞定位,并通过统计学方法分析PCAG1表达水平与前列腺癌的关系。结果 RT-PCR及免疫组化显示PCAG1在前列腺癌组织中的表达明显高于癌旁正常组织,且只在少数几种正常组织中低表达,多数正常组织中无表达,呈现明显的前列腺癌特异高表达的特性;免疫荧光确定PCAG1蛋白主要定位于线粒体中。结论 PCAG1在前列腺癌组织中高表达,提示可能与前列腺癌的发生、发展相关。PCAG1独特的转录调控模式预示其具有潜在的临床应用价值。     

缺氧诱导因子-1α与前列腺癌

新血管的形成和葡萄糖转运、糖酵解的增加是实体肿瘤的两个普遍特性,肿瘤的新血管形成及肿瘤对缺氧微环境的适应与肿瘤的浸润、转移及毁坏性密切相关.     

KAI1与前列腺癌的关系

KAI1是近年从前列腺癌杂交细胞AT6．1－11－1中克隆出的转移抑制基因，编码一种四次跨膜超家族糖蛋白，人体许多组织均有KAI1蛋白表达，其中前列腺组织中含量最丰富，KAI1对多种组织肿瘤有抑制转移作用，其与前列腺癌的关系研究较多，本文主要综述KAI1的主要特征及其与前列腺癌的关系的研究现状。     

Prognostic value of FOXA1 in breast cancer: A systematic review and meta-analysis

BackgroundDespite some published papers analyzing the prognostic role of forkhead-box A1 (FOXA1) in breast cancer, it has not yet been considered as an established prognostic factor in clinical practice. The present meta-analysis evaluated the prognostic value of FOXA1 in breast cancer.MethodsPubMed, Web of Science and Embase databases were searched for relevant published literature that evaluated the correlation between FOXA1 and breast cancer. Either a fixed or random effect model was applied to estimate the pooled hazard ratio (HR) for FOXA1 prognosis in breast cancer.ResultA total of nine articles comprising 6386 breast cancer patients met the inclusion criteria. Among these nine studies, five studies and four studies investigated the prognostic association with disease-free survival (DFS), and overall survival (OS), respectively. Meta-analysis results suggested that high FOXA1 expression was positively associated with DFS (pooled HR: 0.43, 95% CI: 0.23–0.81; P < 0.05) and OS (pooled HR: 0.39, 95% CI: 0.26–0.60; P < 0.05) in breast cancer patients. No publication bias was discovered by Begg's test in this meta-analysis.ConclusionThe results from this meta-analysis indicated that elevated FOXA1 expression level was associated with better outcome in breast cancer.     

PIM-1在前列腺癌组织中的表达及其与PSA的关系

目的:探讨PIM-1蛋白在前列腺癌组织中的表达及其与PSA复发之间的关系。方法:利用免疫组化SP检测68例前列腺癌和37例良性前列腺增生(BPH)组织中PIM-1蛋白的表达。结果:在前列腺癌组织中PIM-1蛋白表达的阳性率为67.65%(46/68);BPH组织中40.54%(15/37),两组表达的差异有显著意义(P<0.05)。PIM-1蛋白表达的阳性率在前列腺癌Gleason分级中6分33.33%(7/21),7分75%(21/28),8～10分94.74%(18/19),组间比较差异有显著性(P<0.05)。临床分期中在Ⅰ、Ⅱ、Ⅲ、Ⅳ期PIM-1蛋白表达率分别为47.62%、53.85%、73.33%、94.74%,36个月随访PSA复发状况采用Kaplan-Meier方法分析,PIM-1蛋白表达与有无复发分别是78.26%(36/46)和45.45%(10/22),差异有显著性(P<0.05)。结论:前列腺癌中PIM-1蛋白表达与前列腺癌的Gleason分级、临床分期以及PSA复发有密切关系,提示PIM-1基因在前列腺癌演化和进展中有重要作用,可能是前列腺癌的预后指标。     

Serial analysis of resected prostate cancer suggests up‐regulation of type 1 IGF receptor with disease progression

What’s known on the subject? and What does the study add? In a previous study of diagnostic prostate biopsies, we showed that the insulin‐like growth factor (IGF) receptor is up‐regulated in primary prostate cancers. In this study we identified prostate cancer cases in which multiple transurethral resections had been performed, and showed that IGF receptor expression increased or remained high with disease progression. Thus, the IGF receptor is an attractive therapeutic target for patients with advanced prostate cancer.

OBJECTIVE

• ? To compare immunostaining protocols using different antibodies for the type 1 insulin‐like growth factor receptor (IGF‐1R) in channel transurethal resection of the prostate (chTURP) chips, and to investigate how IGF‐1R expression varies with time in serial prostate cancer specimens from individual patients.

METHODS

• ? We studied IGF‐1R expression in 44 prostate cancer specimens from 18 patients who had undergone serial chTURP at least 3 months apart.
• ? Retrospective analysis of the hospital notes was undertaken to obtain clinical information, including age, Gleason score, prostate‐specific antigen (PSA) level, hormone treatment and metastatic disease status at the time of each operation.
• ? After an optimization process using three commercially‐available IGF‐1R antibodies, we used two antibodies for semiquantititve immunostaining of serial chTURP chips.

RESULTS

• ? Santa Cruz antibody sc713 gave positive staining in IGF‐1R null R– cells, and was not used further. Antibodies from Cell Signaling Technology (Beverly, MA, USA) (CS) and NeoMarkers Inc. (Fremont, CA, USA) (NM) did not stain R– cells and, in prostate tissue, showed staining of the glandular epithelium, with negligible stromal staining. All 44 chTURP samples contained identifiable malignant tissue and, of these, 73% and 64% scored moderately or strongly (score 3 or 4) with the CS and NM antibodies respectively.
• ? There was significant correlation of IGF‐1R scores of malignant tissue between the two antibodies (P < 0.001). By contrast, staining of benign glands showed poor correlation between antibodies: CS gave significantly weaker staining than malignant epithelium in the same sections (P < 0.001), whereas NM showed poor discrimination between malignant and benign glands. IGF‐1R staining scores generated by the CS antibody were used to analyze the clinical data.
• ? Most patients (six of seven) with falling IGF‐1R staining scores were responding to androgen deprivation therapy (confirmed by PSA response) between operations. Conversely, in seven of eight patients who had progression to androgen‐independence between procedures, IGF‐1R levels increased or remained high. Finally, seven of 11 patients who developed radiologically confirmed metastases between procedures showed stable or increasing IGF‐1R staining scores.

CONCLUSION

• ? The present study is the first to assess changes in IGF‐1R expression in serial prostate cancer samples. The results obtained indicate that IGF‐1R expression usually remains high throughout the course of histologically‐proven disease progression in serial specimens, suggesting that the IGF‐1R remains a valid treatment target for advanced prostate cancer.

     

Down-regulation of human X-box binding protein 1 (hXBP-1) expression correlates with tumor progression in human prostate cancers

BACKGROUND: In our previous study, the gene encoding the human X-box binding protein 1 (hXBP-1) was isolated as a down-regulated gene in advanced prostate cancers using cDNA-representational difference analysis (RDA). In the present investigation, we characterized alterations of hXBP-1 in prostate cancer specimens. METHODS: Expression patterns of hXBP-1 in a series of human prostate cancers were examined by Northern blotting, mRNA in situ hybridization or immunohistochemistry. Loss of heterozygosity (LOH) analysis using microsatellite markers and gene mutation analysis in the hXBP-1 region were also performed. RESULTS: Expression of hXBP-1 was localized in epithelial and adenocarcinoma cells of the prostate. An inverse correlation between hXBP-1 expression and histological differentiation was found in a series of prostate cancers without hormonal therapy. Majority of refractory cancer cases exhibited weak hXBP-1 expression. No allelic loss or gene mutations were found in the hXBP-1 region and its open reading frame, respectively, in the prostate cancer examined. CONCLUSIONS: These results suggest that reduction of hXBP-1 expression may be a useful marker for prostate adenocarcinoma differentiation and progression.     

MTA1基因调控人前列腺癌PC-3细胞失巢凋亡的研究

目的:探讨MTA1基因小干扰RNA(siRNA)对前列腺癌细胞PC-3增殖和失巢凋亡的影响。方法:应用MTA1 siRNA转染处理人前列腺癌细胞系PC-3后,采用实时定量PCR和W estern印迹检测MTA1基因mRNA和蛋白水平,采用软琼脂集落培养试验检测锚着不依赖性增殖,采用琼脂糖凝胶电泳和流式细胞术检测癌细胞失巢凋亡。结果:与对照组比较,MTA1基因siRNA转染组MTA1 mRNA和蛋白水平明显下降,且呈浓度依赖性(r=0.935,P=0.0001)。MTA1 siRNA转染组软琼脂集落形成数明显减少,且与浓度相关(r=0.901,P=0.0005)。琼脂糖凝胶电泳和流式细胞术结果显示,MTA1 siRNA转染可诱导前列腺癌细胞失巢凋亡,且与浓度相关(r=0.916,P=0.0003)。结论:MTA1 siRNA可抑制人前列腺癌细胞增殖,诱导失巢凋亡是其机制之一。