外泌体lncRNA-MIR100HG/miR-100表达变化与胃癌临床病理特征、无疾病进展生存率的相关性

摘要 目的：探究胃癌患者血清外泌体长链非编码RNA-MIR100HG（lncRNA-MIR100HG）及微小核糖核酸-100（miR-100）表达情况,并分析其与患者临床病理特征和无疾病进展生存率之间的相关性。方法：收集60例胃癌患者和60例良性疾病患者,提取外泌体,检测lncRNA-MIR100HG/miR-100的表达情况并进行组间比较。采用Pearson相关分析lncRNA-MIR100HG与miR-100表达水平的相关性,应用单因素卡方检验分析与胃癌患者临床病理特征相关性,采用Kaplan-Meier生存分析lncRNA-MIR100HG/miR-100表达情况与无疾病进展生存率。结果：（1）胃癌组患者血清lncRNA-MIR100HG显著高于,miR-100相对表达水平显著低于胃良性疾病组（P<0.05）;（2）Pearson相关分析结果显示血清lncRNA-MIR100HG和miR-100存在显著负相关关系（r=-0.483,P<0.05）;（3）单因素卡方检验分析结果显示：胃癌患者血清lncRNA-MIR100HG相对表达水平与肿瘤大小、分化程度、肿瘤浸润深度、临床分期、淋巴结转移和远处转移相关,血清miR-100相对表达水平与肿瘤大小、分化程度、临床分期和淋巴结转移相关（P<0.05）;（4）血清lncRNA-MIR100HG、miR-100低水平表达胃癌患者PFS显著长于高水平患者（χ²=37.371,P＜0.05）,miR-100高水平表达胃癌患者PFS显著长于低水平患者（χ²=28.631,P＜0.05）。结论：胃癌患者血清外泌体lncRNA-MIR100HG/miR-100表达水平与肿瘤大小、肿瘤浸润深度、临床分期等病理特征相关,lncRNA-MIR100HG高表达与miR-100低表达可能提示胃癌患者预后越差。     

Snail基因及其蛋白、E-cadherin蛋白在胃癌中的表达及其临床意义

目的观察Snail mRNA及其蛋白、E-cadherin蛋白在胃癌组织中的表达及其与胃癌临床病理特征的关系,并探讨它们在胃癌发生、发展中的作用及其临床应用价值。方法收集96例手术切除胃癌标本,同时取80例癌旁组织作为对照。应用免疫组织化学S-P法检测胃癌组织、癌旁组织中snail蛋白、E-cadherin蛋白的表达;运用原位分子杂交技术检测胃癌组织、癌旁组织中Snail mRNA的表达。结果（1）Snail蛋白在胃癌组织阳性率（83.3%）显著高于癌旁组织（41.25%）（P〈0.05）;高、中分化组Snail蛋白阳性表达率显著低于低分化组（P〈0.05）;Snail蛋白的阳性表达率在乳头状腺癌、管状腺癌及低分化腺癌与黏液癌之间差异有显著性（P〈0.05）;Snail蛋白的表达与胃癌浸润深度、淋巴结转移及远处转移有关（P〈0.05）,与性别、年龄、肿瘤大小、肿瘤部位及临床分期无关（P〉0.05）;（2）胃癌组织中snail mR-NA的阳性率（76%）显著高于癌旁组织（30%）（P〈0.05）;高、中分化组Snail mRNA阳性表达率显著低于低分化组（P〈0.05）;Snail mRNA的阳性表达率在乳头状腺癌、管状腺癌及低分化腺癌与黏液癌之间差异有显著性（P〈0.05）;Snail mRNA的表达与浸润深度及淋巴结转移有关（P〈0.05）,与性别、年龄、肿瘤大小、肿瘤部位、临床分期及远处转移无关（P〉0.05）;（3）E-cadherin蛋白在胃癌组织阳性率（37.5%）显著低于癌旁组织（100%）（P〈0.05）;高、中分化组E-cadherin蛋白阳性率显著高于低分化组（P〈0.05）;E-cadherin蛋白阳性率在乳头状腺癌、管状腺癌及低分化腺癌与黏液癌之间差异有显著性（P〈0.05）;E-cadherin蛋白的表达与胃癌浸润深度、淋巴结转移、临床分期及远处转移有关（P〈0.05）,与性别、年龄、肿瘤大小、肿瘤部位均无关（P〉0.05）;（4）胃癌组织中snail mRNA和snail蛋白的表达呈正相关（r=0.594,P〈0.05）;Snail蛋白和E-cadherin蛋白的表达呈负相关（r=-0.234,P〈0.05）。结论（1）E-cadher-in蛋白低表达与Snail蛋白高表达可能是胃黏膜恶性转变以及胃癌发生浸润转移的重要生物学标志;联合检测E-cadherin蛋白与Snail蛋白对预测胃癌浸润转移有重要意义。（2）Snail蛋白可能在转录水平上调控E-cadherin蛋白的表达。     

胃癌组织长链非编码RNA HIT000218960的表达及其与患者临床病理特征及预后的关系研究

摘要 目的：探讨胃癌组织长链非编码核糖核酸（lncRNA）HIT000218960的表达及其与患者临床病理特征及预后的关系。方法：选择2018年1月至2019年6月于中国人民解放军联勤保障部队第九七Ο医院进行手术切除治疗的103例胃癌患者及进行胃粘膜活检的健康体检志愿者62例,取其对应组织,应用逆转录-定量聚合酶链式反应（RT-qPCR）检测组织中lncRNA HIT000218960及高迁移率族蛋白A2（HMGA2）信使RNA（mRNA）表达,应用免疫组织化学法检测组织中HMGA2阳性表达。分析lncRNA HIT000218960表达与胃癌患者临床病理特征的关系。随访3年,应用Kaplan-Meier生存曲线分析不同lncRNA HIT000218960分组患者预后情况,并应用Cox回归分析胃癌患者预后的影响因素。结果：胃癌组织中lncRNA HIT000218960、HMGA2 mRNA表达水平显著高于正常胃粘膜组织（P<0.05）,HMGA2蛋白阳性表达率显著高于正常胃粘膜组织（P<0.05）。胃癌组织中lncRNA HIT000218960表达与肿瘤直径、组织分化程度、TNM分期、淋巴结转移显著相关（P<0.05）。lncRNA HIT000218960水平与HMGA2 mRNA表达呈正相关（r=0.462,P<0.05）。lncRNA HIT000218960低表达组3年生存率显著高于lncRNA HIT000218960高表达组（P<0.05）。Cox回归显示,肿瘤组织中低分化、TNM分期Ⅲ期、淋巴结转移、lncRNA HIT000218960高表达、HMGA2 mRNA高表达是胃癌患者预后不良的危险因素（P＜0.05）。结论：胃癌组织中存在lncRNA HIT000218960异常高表达,其与胃癌恶性进展及患者预后不良有关。     

PRDX1、HMGA2、FMNL2在胃癌组织中的表达及与临床病理特征、上皮间充质转化和预后的关系研究

摘要 目的：探讨过氧化物酶1（PRDX1）、高迁移率族蛋白A2（HMGA2）、同源形成素样蛋白2（FMNL2）在胃癌组织中的表达及与临床病理特征、上皮-间充质转化（EMT）和预后的关系。方法：选取2017年1月～2018年2月我院收治的153例胃癌患者,收集术中癌组织和癌旁组织。采用免疫组化法检测PRDX1、HMGA2、FMNL2、波形蛋白（VIM）、上皮细胞钙黏蛋白（E-cad）阳性表达情况,采用实时定量PCR（qRT-PCR）法检测PRDX1、HMGA2、FMNL2、VIM、E-cad mRNA相对表达量。分析胃癌组织中PRDX1、HMGA2、FMNL2表达与临床病理特征、EMT和预后的关系。结果：与癌旁组织比较,胃癌组织中PRDX1、HMGA2、FMNL2、VIM阳性表达率和mRNA相对表达量升高,E-cad阳性表达率和mRNA相对表达量降低（P＜0.05）。胃癌组织中PRDX1、HMGA2、FMNL2阳性表达率与患者TNM分期、淋巴结转移、远处转移有关（P＜0.05）。Pearson相关性分析结果显示,胃癌组织中PRDX1、HMGA2、FMNL2 mRNA相对表达量与VIM mRNA相对表达量呈正相关（r=0.562、0.517、0.621,P均＜0.05）,与E-cad mRNA相对表达量呈负相关（r=-0.603、-0.544、-0.574,P均＜0.05）。153例胃癌患者术后3年累积生存率为68.44%（106/153）。Kaplan-Meier生存曲线分析结果显示,PRDX1、HMGA2、FMNL2阳性组术后3年累积生存率均低于阴性组（P＜0.05）。结论：胃癌组织中PRDX1、HMGA2、FMNL2表达升高,其表达与TNM分期、淋巴结转移、远处转移、EMT以及预后有关,可作为胃癌病情和预后的辅助评估指标。     

食管癌组织环指蛋白2、环指蛋白6的表达与上皮-间质转化和预后的关系分析

摘要 目的：探讨食管癌组织环指蛋白2（RNF2）、环指蛋白6（RNF6）的表达与上皮-间质转化（EMT）和预后的关系。方法：选择广东医科大学附属医院2017年2月至2020年2月收治的162例食管癌患者,取手术切除的癌组织和癌旁组织。采用免疫组化法检测RNF2、RNF6以及EMT标志蛋白[上皮钙黏附素（E-cadherin）、神经型钙黏蛋白（N-cadherin）Slug 和Snail]表达。Spearman相关性分析RNF2、RNF6与EMT标志蛋白的关系;分析食管癌组织RNF2、RNF6表达在不同临床病理特征中的差异;Kaplan-Meier生存曲线分析RNF2、RNF6表达与食管癌患者预后的关系;多因素Cox回归分析影响食管癌患者预后的因素。结果：食管癌组织RNF2、RNF6、N-cadherin、Slug和Snail蛋白阳性表达率高于癌旁组织,E-cadherin蛋白阳性表达率低于癌旁组织（P＜0.05）。食管癌组织RNF2、RNF6蛋白阳性表达率与N-cadherin、Slug和Snail蛋白阳性表达率呈正相关,与E-cadherin蛋白阳性表达率呈负相关（P＜0.05）;低度分化、TNM分IIIA期、肿瘤直径≥2 cm、淋巴结转移在食管癌组织中RNF2、RNF6蛋白阳性表达率高于无淋巴结转移、肿瘤直径＜2 cm,中高度分化、TNM分期I～II期食管癌组织（P＜0.05）;RNF2阳性表达患者3年OS率为47.17%,低于RNF2阴性表达患者的59.26% （P＜0.05）,RNF6阳性表达患者3年OS率为47.06%,低于RNF6阴性表达患者的63.41%（P＜0.05）;多因素Cox回归分析显示TNM分期ⅢA期、淋巴结转移、RNF2阳性表达、RNF6阳性表达是食管癌患者预后的危险因素（P＜0.05）。结论：食管癌组织中RNF2、RNF6阳性表达率增加,且与肿瘤直径、分化程度、TNM分期、淋巴结转移以及低生存率有关,RNF2、RNF6可能通过EMT参与食管癌恶性进展过程。     

血清载脂蛋白AI、鳞状细胞癌抗原与子宫内膜癌病理特征的关系及对淋巴结转移的预测研究

摘要 目的：分析血清载脂蛋白AI、鳞状细胞癌抗原与子宫内膜癌病理特征的关系及对淋巴结转移的预测价值。方法：选择我院自2020年7月至2022年7月收治的156例行手术治疗的子宫内膜癌患者作为研究对象,检测血清载脂蛋白AI、鳞状细胞癌抗原表达水平,分析不同临床分期、病理分级、子宫肌层浸润程度的子宫内膜癌血清载脂蛋白AI、鳞状细胞癌抗原表达水平的差异性,比较淋巴结转移组与非淋巴结转移组血清载脂蛋白AI、鳞状细胞癌抗原表达水平,通过受试者工作特征曲线（ROC）下面积（AUC）评价血清载脂蛋白AI联合鳞状细胞癌抗原对子宫内膜癌患者发生淋巴结转移的预测价值。结果：Ⅲ～Ⅳ期组血清载脂蛋白AI低于Ⅰ～Ⅱ期组,鳞状细胞癌抗原表达水平高于Ⅰ～Ⅱ期组（P＜0.05）;中低分化组血清载脂蛋白AI水平低于高分化组,鳞状细胞癌抗原表达水平高于高分化组（P＜0.05）;子宫肌层浸润≥1/2组血清载脂蛋白AI水平低于子宫肌层浸润＜1/2组,鳞状细胞癌抗原表达水平高于子宫肌层浸润＜1/2组（P＜0.05）;在120例子宫内膜癌患者中,发生淋巴结转移28例;淋巴结转移组血清载脂蛋白AI低于非淋巴结转移组,鳞状细胞癌抗原表达水平高于非淋巴结转移组（P＜0.05）;经ROC曲线分析,血清载脂蛋白AI联合鳞状细胞癌抗原预测子宫内膜癌患者发生淋巴结转移的AUC为0.910。结论：血清载脂蛋白AI、鳞状细胞癌抗原与子宫内膜癌的不同临床分期、病理分级、子宫肌层浸润程度有关,术前检测两者表达水平有助于淋巴结转移的预测,对于指导临床治疗具有积极作用。     

幽门螺旋杆菌阳性胃癌组织microRNA-1290、microRNA-134表达与肿瘤增殖基因、侵袭基因和预后的关系分析

摘要 目的：探讨幽门螺旋杆菌（Hp）阳性胃癌组织中微小核糖核酸-1290（miR-1290)、微小核糖核酸-134（miR-134）的表达及其与肿瘤增殖基因、侵袭基因和预后的关系。方法： 选取2016年1月至2017年1月重庆大学附属三峡医院收治的126例胃癌患者为研究对象，根据Hp检测结果分为Hp阳性胃癌组（n=84）和Hp阴性胃癌组（n=42），另同期60例慢性胃炎患者为对照组。实时荧光定量聚合酶链反应检测各组组织中miR-1290、miR-134、增殖基因[磷脂酰肌醇3催化亚基A（PIK3CA）、C-myc癌基因（c-myc）]和侵袭基因[碱性螺旋环-螺旋转录因子(Twist)、N钙黏素（N-cad）]的表达。Pearson相关分析Hp阳性胃癌组织miR-1290、miR-134与肿瘤增殖PIK3CA、c-myc和侵袭基因Twist、N-cad表达的相关性，比较不同临床病理特征Hp阳性胃癌患者miR-1290、miR-134表达差异。Kaplan-Meier生存曲线评估miR-1290、miR-134表达与Hp阳性胃癌患者生存预后的关系。结果：Hp阳性胃癌组患者癌组织miR-1290表达高于Hp阴性胃癌组癌组织及对照组胃粘膜组织，miR-134表达低于Hp阴性胃癌组癌组织及对照组胃粘膜组织，差异有统计学意义(P<0.05)。Hp阳性胃癌组织中miR-1290表达与增殖基因PIK3CA、c-myc和侵袭基因Twist、N-cad mRNA表达呈正相关性（r=0.620～0.725，均P<0.05），miR-134与增殖基因PIK3CA、c-myc和侵袭基因Twist、N-cad mRNA表达呈显著负相关性（r=-0.670～-0.784，均P<0.05）。不同肿瘤TNM分期、浸润深度及淋巴结转移Hp阳性胃癌患者癌组织中miR-1290、miR-134表达比较，差异具有统计学意义(P均<0.05) 。Hp阳性胃癌组患者中，miR-1290高表达组和低表达组5年总体生存率分别为48.78%（20/41），75.61%（31/41）。miR-1290高表达组患者累积生存率明显低于miR-1290低表达组(Log rank χ²=6.366，P= 0.012)。miR-134低表达组和高表达组患者5年总体生存率分别为42.86%（18/42），82.50%（33/40）。miR-134低表达组累积生存率显著低于miR-134高表达组(Log rank χ²=10.640，P=0.001)。结论：Hp阳性胃癌组织miR-1290表达增加，miR-134表达降低，两者可能通过促进肿瘤增殖和侵袭基因的表达，导致肿瘤恶性进展及不良预后。     

Snail1基因表达在妊娠期糖尿病大鼠氧化应激及肝脏损伤的作用机制

摘要 目的：探讨Snail1基因表达在妊娠期糖尿病大鼠氧化应激及肝脏损伤的作用机制。方法：健康成年C57BL/6雌性大鼠32只作为研究对象。采用高脂喂养联合小剂量链脲佐菌素注射的方式构建妊娠期糖尿病大鼠模型。将所有大鼠分为正常妊娠组,正常妊娠+Snail1过表达组,妊娠期糖尿病组,妊娠期糖尿病+Snail1过表达组。采用qRT-PCR检测大鼠Snail1的mRNA表达水平,并检测大鼠妊娠期体重、氧化应激指标、炎症指标和肝功能指标。结果：与正常妊娠组相比,正常妊娠+Snail1过表达组、妊娠期糖尿病组、妊娠期糖尿病+Snail1过表达组的孕鼠体重、胎鼠体重、胎盘重量、Snail1 mRNA,明显更高（P＜0.05）,且妊娠期糖尿病+Snail1过表达组孕鼠体重、胎鼠体重、胎盘重量、Snail1 mRNA均显著高于正常妊娠+Snail1过表达组和妊娠期糖尿病组（P＜0.05）;与正常妊娠组相比,正常妊娠+Snail1过表达组、妊娠期糖尿病组、妊娠期糖尿病+Snail1过表达组的FBG、FINS、HOMA-IR明显更高（P＜0.05）,且妊娠期糖尿病+Snail1过表达组FBG、FINS、HOMA-IR均显著高于正常妊娠+Snail1过表达组和妊娠期糖尿病组（P＜0.05）;与正常妊娠组相比,正常妊娠+Snail1过表达组、妊娠期糖尿病组、妊娠期糖尿病+Snail1过表达组的ROS、GSH-Px、MDA明显更高（P＜0.05）,且妊娠期糖尿病+Snail1过表达组ROS、GSH-Px、MDA均显著高于正常妊娠+Snail1过表达组和妊娠期糖尿病组（P＜0.05）;与正常妊娠组相比,正常妊娠+Snail1过表达组、妊娠期糖尿病组、妊娠期糖尿病+Snail1过表达组的TNF-α、IL-1β、IL-18明显更高（P＜0.05）,且妊娠期糖尿病+Snail1过表达组TNF-α、IL-1β、IL-18均显著高于正常妊娠+Snail1过表达组和妊娠期糖尿病组（P＜0.05）;与正常妊娠组相比,正常妊娠+Snail1过表达组、妊娠期糖尿病组、妊娠期糖尿病+Snail1过表达组的GPT、GOT、ALP明显更高（P＜0.05）,且妊娠期糖尿病+Snail1过表达组GPT、GOT、ALP均显著高于正常妊娠+Snail1过表达组和妊娠期糖尿病组（P＜0.05）。结论：妊娠期糖尿病大鼠Snail1基因的表达上调可加重糖脂代谢紊乱,并激活下游氧化应激和炎症反应,进而加重大鼠肝脏损伤。     

脑胶质瘤组织长链非编码RNA FTX、RHPN1-AS1表达与预后的关系

摘要 目的：探讨脑胶质瘤组织长链非编码核糖核酸(LncRNA) FTX、RHPN1-AS1表达与预后的关系。方法：选取我院105例脑胶质瘤患者手术切除的癌组织和癌旁组织（距离肿瘤边缘3~5 cm）。采用实时荧光定量PCR（qRT-PCR）检测组织中LncRNA FTX、RHPN1-AS1表达。分析LncRNA FTX、RHPN1-AS1表达与脑胶质瘤患者临床病理特征的关系。K-M法绘制不同LncRNA FTX、RHPN1-AS1表达脑胶质瘤患者术后5年无进展生存期和总生存期曲线。Cox回归分析脑胶质瘤患者预后不良的影响因素。结果：脑胶质瘤组织中LncRNA FTX、RHPN1-AS1表达水平高于癌旁组织(P＜0.05)。LncRNA FTX、RHPN1-AS1表达与脑胶质瘤患者卡氏体力状态(KPS)评分和世界卫生组织(WHO)分级相关(P＜0.05)。LncRNA FTX、RHPN1-AS1高表达组无进展生存期和总生存期均短于低表达组(P＜0.05)。KPS评分(HR=2.621,95%CI：1.284～5.348)、WHO分级(HR=2.264,95%CI：1.152～4.449)、LncRNA FTX(HR=1.997,95%CI：1.017～3.922)、LncRNA RHPN1-AS1(HR=2.431,95%CI：1.257～4.701)均是脑胶质瘤患者预后不良的影响因素(P＜0.05)。结论：脑胶质瘤组织中LncRNA FTX、RHPN1-AS1表达水平升高,且二者与KPS评分、WHO分级均是患者预后不良的影响因素,可用于脑胶质瘤患者预后评估。     

Expression and Prognostic Value of miR-486-5p in Patients with Gastric Adenocarcinoma

MicroRNA (miR)-486-5p expression is often reduced in human cancers. However, its expression in gastric carcinoma and its relation to clinicopathological features and prognosis are unclear. Tissue microarrays were constructed from 84 patients with gastric adenocarcinoma (GC) who were undergoing radical resection. miR-486-5p expression was detected by miRNA-locked nucleic acid in situ hybridization, and its correlations with clinicopathological features and overall survival were analyzed. Bioinformatic studies predict that fibroblast growth factor 9 (FGF9) is a potential target gene of miR-486-5p. miR-486-5p was mainly located in the cytoplasm of GC cells and neighboring normal tissues. Compared with paracancerous normal tissue, miR-486-5p expression was decreased in 63.1% (53/84) of the GC samples, increased in 32.1% (27/84) and unchanged in 4.8% (4/84). FGF9 expression was decreased in 69.0% (58/84) of GC samples and increased in 31.0% (26/84) compared with normal paracancerous tissues using immunohistochemical analysis. Low or unchanged miR-486-5p expression (P = 0.002), tumor stage (P = 0.001), tumor status (P = 0.001), node status (P = 0.001), tumor size (P = 0.004), and depth of tumor invasion (P = 0.013) were significant negative prognostic predictors for overall survival in patients with GC. After stratification according to American Joint Committee on Cancer (AJCC) stage, low/unchanged miR-486-5p expression remained a significant predictor of poor survival in stage II (P = 0.024) and stage III (P = 0.003). Cox regression analysis identified the following predictors of poor prognosis: tumor status (hazard ratio [HR], 7.19; 95% confidence interval [CI], 1.75–29.6; P = 0.006), stage (HR, 2.62; 95%CI, 1.50–4.59; P = 0.001), lymph node metastasis (HR, 2.52; 95% CI, 1.27–4.99; P = 0.008), low/unchanged miR-486-5p (HR, 2.47; 95% CI, 1.35–4.52; P = 0.003), high level of FGF9 (HR, 2.41; 95% CI, 1.42–4.09; P = 0.001) and tumor size (HR, 2.50; 95% CI, 1.30–4.82; P = 0.006). Low or unchanged expression of miR-486-5p compared with neighboring normal tissues was associated with a poor prognosis, while high expression was associated with a good prognosis in GC. miR-486-5p may thus be useful for evaluating prognosis and may provide a novel target treatment in patients with GC.     

氨基酸转运载体SLC1A5在胃癌组织中的表达及其临床病理学意义

目的:研究氨基酸转运载体溶质载体家族1成员5(Solute Carrier Family 1 Member 5, SLC1A5)蛋白在胃癌组织中的表达情况,并探讨其与胃癌临床病理特征及预后的相关性。方法:收集进展期胃癌组织及对应癌旁组织90例,应用免疫组化技术检测SLC1A5在上述组织中的表达情况,并统计分析其表达与胃癌临床病理特征及预后的关系。同时通过基因数据库分析SLC1A5在胃癌组织和癌旁组织中表达情况及其对胃癌患者预后的影响。结果:与癌旁组织相比,胃癌组织中SLC1A5表达明显上调(P0.0001)。数据库研究也显示SLC1A5在胃癌组织中表达明显上调(GSE 65801,P=0.0046;GSE 63809,P0.0001;GSE 27342,P=0.0147)。胃癌组织中SLC1A5高表达与肿瘤大小(P0.05)、肿瘤浸润深度(P0.01)、淋巴结转移(P0.05)、TNM分期(P0.05)和Ki-67(P0.01)相关,而与年龄、性别、肿瘤位置及分化程度均无显著相关性(P0.05)。胃癌组织中SLC1A5表达强度与患者预后相关,表达越高,患者预后越差(总体生存率,P=0.0131;无复发生存率,P=0.0293)。数据库分析也显示SLC1A5高表达可明显缩短患者的总体生存期(GSE 14210,P=0.011;GSE 22377,P=0.0015)和无进展生存期(GSE 14210,P=0.0095;GSE 22377,P=0.0012)。结论:SLC1A5蛋白表达在胃癌组织中明显上调,且与肿瘤大小、肿瘤浸润深度、淋巴结转移及TNM分期有关。SLC1A5高表达与胃癌患者预后不良密切相关。     

子宫内膜癌组织KIF23、LAPTM4B、Snail表达与患者临床病理参数及预后的关系

目的:探讨子宫内膜癌组织驱动蛋白家族成员23(KIF23)、溶酶体相关4次跨膜蛋白质β(LAPTM4B)、Snail表达与患者临床病理参数及预后的关系。方法:选择2012年10月至2015年2月期间在我院治疗的130例子宫内膜癌患者进行临床研究,采用免疫组织化学染色法检测KIF23、LAPTM4B、Snail的表达,分析KIF23、LAPTM4B、Snail的表达与各项临床病理参数及预后的关系。Cox比例风险回归分析子宫内膜癌患者预后的影响因素。结果:子宫内膜癌组织中KIF23、LAPTM4B、Snail阳性率明显高于癌旁正常组织(x~2=61.356、67.031、82.028,均P=0.000)。子宫内膜癌组织中KIF23、LAPTM4B、Snail表达与淋巴结转移、肌层浸润和FIGO分期相关(P0.05)。KIF23、LAPTM4B、Snail阳性患者5年总生存率明显低于KIF23、LAPTM4B、Snail阴性患者(P0.05)。FIGO分期、KIF23、LAPTM4B和Snail是子宫内膜癌患者预后的影响因素(HR=1.409、1.478、1.523、2.178,P0.05)。结论:KIF23、LAPTM4B和Snail在子宫内膜癌中阳性表达率升高,并且均与子宫内膜癌淋巴结转移、肌层浸润、FIGO分期和预后相关,在子宫内膜癌的诊断和预后评估中具有一定临床意义。     

Overexpression of the Receptor for Advanced Glycation Endproducts (RAGE) Is Associated with Poor Prognosis in Gastric Cancer

Background

The receptor for advanced glycation endproducts (RAGE) is an oncogenic multidisciplinary trans-membranous receptor, which is overexpressed in multiple human cancers. Recently, it has been shown that RAGE is also involved in carcinogenesis and tumor invasion. In this study, we investigated the expression levels and prognostic value of RAGE in primary gastric cancers (GC).

Methods

We investigated RAGE expression in primary GC and paired normal gastric tissue by real-time quantitative RT-PCR (n = 30) and Western blotting analysis (n = 30). Additionally, we performed immunohistochemistry on 180 paraffin-embedded GC specimens, 69 matched normal specimens.

Results

RAGE was overexpressed in GC compared with the adjacent noncancerous tissues (P＜0.001), and higher RAGE expression significantly correlated with the histological grade (P = 0.002), nodal status(P = 0.025), metastasis status(P = 0.002), and American Joint Committee on Cancer stage (P = 0.020). Furthermore, upregulation of RAGE expression is an independent prognostic factor in multivariate analysis using the Cox regression model (P = 0.001).

Conclusions

RAGE Overexpression may be a useful marker to predict GC progression and poor prognosis.     

Poor Prognosis of Phosphatase of Regenerating Liver 3 Expression in Gastric Cancer: A Meta-Analysis

Background

Overexpression of phosphatase of regenerating liver 3 (PRL-3) has been implicated in gastric cancer (GC) metastasis. Epidemiological studies have evaluated the relationship between PRL-3 expression and prognosis in GC. However, results still remains controversial. In this study, a meta-analysis was performed to evaluate the association of PRL-3 expression with overall survival (OS) and clinicopathological characteristics.

Methods

Literature databases were searched to identify eligible studies dated until April 2013. Summary hazard ratios (HRs) or odds ratios (ORs) with 95% confidence interval (95% CI) were calculated to estimate the association.

Results

A total of 1380 GC patients from six studies were included in the meta-analysis. Overall, the combined HR estimate for OS in a random-effect model was 1.89 (95% CI = 1.38–2.60; P<0.001). Results showed that PRL-3 overexpression was significantly associated with OS, indicating that it may be a biomarker for poor prognosis of GC. Both subgroup and sensitivity analyses further identified the prognostic role of PRL-3 expression in GC patients. Moreover, PRL-3 overexpression was significantly associated with tumor stage (OR = 2.25; 95% CI = 1.63–3.12; P<0.001), depth of invasion (OR = 2.03; 95% CI = 1.38–2.98; P<0.001), vascular invasion (OR = 2.52; 95% CI = 1.79–3.56; P<0.001), lymphatic invasion (OR = 3.74; 95% CI = 2.49–5.63; P<0.001), and lymph node metastasis (OR = 4.56; 95% CI = 2.37–8.76; P<0.001). However, when age, sex, tumor size, and tumor differentiation were considered, no obvious association was observed.

Conclusions

This meta-analysis reveals significant association of PRL-3 overexpression with OS and some clinicopathological features in GC. PRL-3 may be a predicative factor of poor prognosis and aggressive tumor behavior in GC patients.     

Ⅰ型子宫内膜癌组织中HIF-1α、Snail与E-cadherin的表达及临床意义

目的探讨I型子宫内膜癌组织中HIF-1α的表达,以及调控Snail和E-cadherin对肿瘤侵袭性生物学行为的影响。方法采用免疫组化方法,结合组织芯片技术,检测124例I型子宫内膜癌、28例内膜不典型增生、35例正常内膜组织中HIF-1α、Snail和E-cadherin的表达水平,分析三种蛋白表达之间的相关性及与临床病理因素的关系。结果 I型子宫内膜癌组织中HIF-1α、Snail和E-cadherin的表达率分别为61.3%、46.8%、36.3%,与正常内膜和不典型增生内膜组织相比,有显著统计学差异(P<0.01)。HIF-1α表达与病理分级、肿瘤肌层浸润和淋巴结转移明显相关(P<0.05)。Snail表达与FIGO分期、淋巴结转移明显相关(P<0.05)。E-cadherin的缺失与肿瘤肌层浸润和淋巴结转移显著相关(P<0.01)。I型子宫内膜癌组织中HIF-1α和Snail的表达呈明显正相关(r=0.214,P=0.017),而Snail和E-cadherin的表达存在负相关关系(r=–0.203,P=0.024)。结论 HIF-1α可能通过上调Snail的表达和抑制E-cadherin的表达在I型子宫内膜癌发生、侵袭和转移中发挥重要作用。     

The co-expression of USP22 and BMI-1 may promote cancer progression and predict therapy failure in gastric carcinoma

Recent experimental evidence support the model in which the simultaneous induction of BMI-1 and USP22 is critical during cancer progression. Whether this model may affect gastric cancer (GC) progression is worthy of additional study. In this study, we examined the significance of the USP22 and BMI-1 expression in GC (n = 219), non-cancerous mucosa (n = 37), and lymph node metastasis (n = 37). The protein expression level of USP22 and BMI-1 were concomitantly up-regulated from non-cancerous mucosa to primary carcinoma and from carcinomas to lymph node metastasis (P < 0.001). A statistical correlation was observed between USP22 and BMI-1 expression in GC tissues (n = 219, r = 0.634, P < 0.001) and in lymph node metastasis (n = 37, r = 0.689, P < 0.001). The incidence of positive expression was 57.08% for USP22, 49.32% for BMI-1, and 45.21% for USP22/BMI-1 in 219 GC tissues, respectively. Co-positive of USP22/BMI-1 was significantly correlated with gross features (x(2) = 14.256, P < 0.001), differentiation (x(2) = 5.872, P = 0.015), pT classification (x(2) = 18.486, P < 0.001), pN classification (x(2) = 9.604, P = 0.002), pM classification (x(2) = 32.766, P < 0.001), and AJCC stage (x(2) = 58.278, P < 0.001). Notably, high USP22/BMI-1 expression was significantly associated with shorter disease-specific survival (P < 0.001). By Cox regression analysis, co-positive of USP22/BMI-1 was found to be an independent prognostic factor (P = 0.002). Our results indicated the simultaneous activation of USP22 and BMI-1 may associate with GC progression and therapy failure.     

Analysis of Sex Differences in Cancer-Specific Survival and Perioperative Mortality Following Radical Cystectomy: Results of a Large German Multicenter Study of Nearly 2500 Patients with Urothelial Carcinoma of the Bladder

BackgroundOutcome of patients with urothelial carcinoma of the bladder (UCB) varies between sexes. Although overall incidence is higher in men, cancer-specific survival (CSS) has been suggested to be lower in women. Although the former effect is attributed to greater exposure to carcinogens in men, the latter has not been elucidated.ObjectivesThe aim of the study was to identify sex-specific outcomes based on one of the largest databases of patients with UCB who underwent radical cystectomy (RC).MethodsThis retrospective multicenter series comprised 2483 patients in Stage M0 who underwent RC for UCB from 1989 to 2008; 20.4% of patients were women. The impact of sex on CSS in the entire study group and in specific subgroups was analyzed. The median follow-up time was 42 months (interquartile range, 21–79).ResultsHistopathologic criteria of pathologic tumor (pT), pathologic nodal (pN), grade, lymphovascular invasion (LVI), and associated carcinoma in situ (CIS) of the study did not differ between sexes. The percentage of female patients increased over time. Five-year CSS in female patients was significantly lower than in male patients (60% vs 66%; P = 0.005). In multivariate analysis adjusted to other covariates, tumor stage ≥pT3 (hazard ratio [HR] = 2.44; P < 0.001), positive pN status (HR = 1.91; P < 0.001), LVI (HR = 1.48; P < 0.001), lower count of lymph nodes removed (HR = 0.98; P = 0.002), older age (HR = 1.01; P < 0.001), and female gender (HR = 1.26; P = 0.011) had an independent impact on CSS. Deterioration of CSS in female patients was pronounced when LVI was present (HR = 1.57; P < 0.001) and when RC was performed in the earlier time period (HR = 2.44; P < 0.001). However, women showed significantly lower perioperative mortality (within 90 days after RC) compared with men.ConclusionsAfter RC for UCB, cancer-specific mortality was higher in female patients; this disadvantage was more pronounced in earlier time periods. In addition, worse outcome of women with verified LVI was shown to be comparable with men. These findings were suggestive of different tumor biology and potentially unequal access to timely RC in earlier time periods because of reduced awareness of UCB in women. Further studies are required to improve UCB outcome in both sexes, notably in female patients.     

Kallistatin在乳腺癌中表达的临床病理意义

目的:探讨Kallistatin在乳腺癌中表达的临床病理意义及预后价值。方法:收集乳腺癌档案蜡块及临床资料,分为无淋巴结转移的原发灶(NMBT),有淋巴结转移的原发灶(PBT)及配对的淋巴结转移灶(PMLN),应用免疫组化技术检测Kallistatin表达,统计学分析。结果:结果显示kallistatin在PBT组的表达高于NMBT组合和PMLN组。kallistatin的表达与组织学类型(P=0.003)、淋巴结状态(P0.001)、临床分期(P=0.002)、雌激素受体(ER)表达(P=0.046)有显著相关性。kallistatin在浸润性小叶癌中的阳性表达率高于浸润性导管癌,在PBT组的阳性表达率显著高于NMBT,临床分期越晚期阳性表达率越高,在ER阳性的病历中表达更高。Kaplan-Meier分析显示,kallistatin的阳性表达是乳腺癌患者无病生存时间短(P=0.008)和总生存时间短(P=0.006)的危险因素。在浸润性乳腺导管癌患者中,kallistatin的阳性表达与生存时间短有关(P=0.026)。还与ER阳性表达患者生存时间较短有关(P=0.010)。结论:Kallistatin在乳腺癌中的表达有较为复杂的临床病理意义,其表达提示预后不良。     

GJA1在结直肠癌组织中表达及促进侵袭转移的研究

摘要 目的：间隙连接Alpha-1蛋白（Gap Junction Alpha-1,GJA1）是间隙连接中分布最广泛的蛋白,并在多种肿瘤中起促癌作用,但其在结直肠癌发生、发展的作用研究甚少。本实验旨在探究GJA1在结直肠癌组织中的表达情况及其对结直肠癌细胞系侵袭、转移能力的影响,以期为结直肠癌的诊断和预后寻找新的生物标志物。方法：收集92对结直肠癌及其癌旁组织样本,提取组织RNA,利用qRT-PCR检测GJA1相对表达量,并分析GJA1表达与临床病理特征及预后的相关性。在HCT116和HCT8两种结直肠癌细胞系中分别构建GJA1过表达载体和敲减载体,利用qRT-PCR和、Western Blot检测上皮间充质转化（epithelial-mesenchymal transition, EMT）相关蛋白E-Cadherin、N-Cadherin、Vimentin和Snail的表达变化,利用Wound healing和Transwell实验观察其迁移、侵袭能力的变化。结果：相对于癌旁组织,GJA1在结直肠癌组织中显著低表达。并且结直肠癌中低表达的GJA1与肿瘤分化程度、浸润深度、淋巴血管转移相关,低表达GJA1结直肠癌患者显示更差的总体生存率和更低的无病生存率。此外,过表达GJA1后,结直肠癌细胞E-cadherin的表达升高,N-cadherin、Vimentin和Snail的表达降低,划痕愈合减慢,Transwell转移细胞减少;而敲减GJA1后,结直肠癌细胞E-Cadherin的表达降低,N-Cadherin、Vimentin和Snail的表达升高,划痕愈合加快,Transwell转移细胞增多。结论：GJA1在结直肠癌中低表达,其表达降低可通过EMT促进结直肠癌的侵袭、转移并影响病人预后。