黑色素瘤缺乏因子2 在胆管癌组织中的表达及其临床意义

目的:研究黑色素瘤缺乏因子2(AIM2)在胆管癌组织中的表达,并分析其表达水平与胆管癌患者临床病理特征及预后的关系。方法:采用组织芯片技术和免疫组织化学染色法,分别检测91例胆管癌组织及其部分正常组织中AIM2的表达水平,采用Wilcoxon秩和检验比较癌组织及正常组织中AIM2表达水平的差异,采用χ~2检验分析胆管癌组织中AIM2表达水平与患者临床病理特征的关系,采用Kaplan-Meier法分析胆管癌组织中AIM2表达水平与患者总生存期的关系,拟合Cox模型评价不同指标的预后价值。结果:AIM2在正常组织中高表达(P0.005),而在胆管癌组织中以不表达和低表达为主;AIM2的表达水平与肿瘤大小显著相关(χ~2=7.380,P=0.007);AIM2低表达的胆管癌患者总生存期(OS)较AIM2高表达水平的患者显著缩短(HR=0.293,95%CI:0.130～0.662,P=0.002);多因素Cox风险比例模型显示,AIM2表达水平(HR=0.320,95%CI:0.120～0.853,P=0.023)、性别(HR=2.268,95%CI:1.019～5.044,P=0.041)和年龄(HR=0.180,95%CI:0.070～0.465,P=0.000)均可作为胆管癌患者预后评判的独立风险因素。结论:AIM2在胆管癌组织中呈低表达,有望成为胆管癌患者的预后预测指标。     

肝细胞癌组织中IMP3与IGF2表达对预后评估的临床病理学意义

目的 探讨癌基因胰岛素样生长因子2 mRNA结合蛋白3(insulin-like growth factor 2 mRNA binding protein 3,IMP3)和胰岛素样生长因子2(insulin-like growth factor 2,IGF2)在肝细胞癌(hepatocellular carcinoma,HCC)组织中表达的预后意义.方法 采用免疫组化SP法对92例HCC及其癌旁良性组织中IMP3及IGF2的表达进行检测,结合临床生物学指标及生存时间进行统计学分析.结果 HCC组织中IMP3和IGF2阳性率均明显高于癌旁组织(P均<0.01);IMP3表达与组织分化程度、是否转移、ACJJ分期、门脉癌栓及Ki-67表达均密切相关;IGF2的表达与肿瘤组织学分级和Ki-67蛋白表达相关(P均<0.05).IMP3与IGF2表达呈显著正相关(rs=0.265,P<0.05).生存分析显示,IMP3阳性表达的患者总生存期明显低于不表达的患者(Log-rank=16.854,P=0.000);IMP3和IGF2同时表达与二者单独表达的患者生存期差异有统计学意义(P=0.000和0.008).进一步分析证明IMP3是HCC生存期的独立影响因素(HR:0.473,95%CI:0.270～0.829,P=0.009).结论 联合检测HCC组织中IMP3和IGF2的表达对其诊断及预后有一定的价值,二者可能成为HCC生物标记中的新指标.     

IGF-1R-Stat3信号通路通过激活中期因子表达促进肝癌细胞活力、迁移和侵袭

目的:探讨胰岛素样生长因子1受体(IGF-1R)-信号转导及转录激活蛋白3(Stat3)信号通路和中期因子(midkine)在肝细胞癌中的作用以及IGF-1R-Stat3信号通路与midkine表达之间的关系。方法:(1)采用RTqPCR检测人肝癌细胞株Huh7和Hep3B、人正常肝细胞株HL-7702、人肝细胞癌组织(n=32)、配对的癌旁组织(n=32)及正常成人肝组织(n=13)中IGF-1R、Stat3和midkine的mRNA表达水平,并应用Pearson相关分析评估肝细胞癌组织中三者表达水平之间的关系。(2)以Huh7细胞作为空白对照,在瞬时上调IGF-1R表达、稳定敲减IGF-1R表达及稳定敲减IGF-1R表达+瞬时上调Stat3表达的Huh7细胞中,采用RT-qPCR及Western blot检测Stat3和midkine mRNA表达水平及Stat3、磷酸化Stat3和midkine蛋白水平;以Huh7细胞作为空白对照,在瞬时上调或瞬时敲减Stat3表达的Huh7细胞中,采用RT-qPCR及Western blot分别检测midkine mRNA和蛋白表达水平。(3)采用MTT法和Transwell实验检测IGF-1R-Stat3信号通路和midkine表达变化对Huh7细胞活力、迁移和侵袭的影响。结果:分别与正常肝细胞和癌旁组织/正常肝组织相比,肝癌细胞株和肝细胞癌组织中IGF-1R、Stat3和midkine的mRNA表达水平显著升高(P0. 01);肝细胞癌组织中Stat3和midkine的mRNA表达水平均与IGF-1R的mRNA表达水平呈正相关(r=0. 716和r=0. 681,P0. 01),midkine mRNA表达水平与Stat3 mRNA表达水平也呈正相关(r=0. 657,P0. 01)。在Huh7细胞中,IGF-1R通过上调Stat3表达并增加其磷酸化水平而促进midkine表达(P0. 01);而且IGF-1R通过激活Stat3、上调midkine表达而增强细胞活力、迁移能力和侵袭能力(P0. 01)。结论:IGF-1R-Stat3信号通路通过激活midkine表达增强肝癌细胞活力,促进细胞迁移和侵袭。     

卵巢浆液性肿瘤中IGF-2R的表达及其意义

目的探讨胰岛素生长因子受体-2(insulin-like growth factor-2 receptor,IGF-2R)的表达及其与卵巢浆液性肿瘤临床病理特征的关系,分析IGF-2R表达对卵巢浆液性肿瘤的诊断及预后价值。方法收集10例正常卵巢上皮组织、15例良性浆液性卵巢肿瘤、15例交界性卵巢浆液性肿瘤及46例卵巢浆液性腺癌,采用免疫组化SP三步法检测IGF-2R的表达。结果 IGF-2R在100%(10/10)的正常卵巢上皮、93.3%(14/15)的良性浆液性卵巢肿瘤、86.7%(13/15)的交界性浆液性卵巢肿瘤和47.8%(22/46)的浆液性卵巢癌中呈阳性。IGF-2R在正常卵巢上皮组织与良性浆液性肿瘤组织中的表达差异无统计学意义(双侧P=0.405),IGF-2R在浆液性卵巢癌与交界性肿瘤、良性浆液性肿瘤、正常卵巢上皮组织中的表达差异有统计学意义(双侧P=0.008;P=0.002,P=0.003),IGF-2R表达与卵巢浆液癌临床分期、转移情况有关(P=0.003,P=0.032),与患者年龄、病理学分级、生存状态无关(P=0.181,P=0.180,P=0.118)。结论IGF-2R在卵巢表面上皮、良性浆液性肿瘤、交界性浆液性肿瘤和浆液性癌中表达呈逐步下调趋势。IGF-2R表达与卵巢浆液性腺癌的高临床分期、淋巴结转移呈负相关,可能成为卵巢浆液性肿瘤辅助诊断及临床预后的新指标。     

福建汉族胰岛素样生长因子受体基因多态性与非小细胞肺癌易感性的关联研究

目的 探讨胰岛素样生长因子受体(insulin-like growth factor receptor,1GF-1R和IGF-2R)基因多态性与福建汉族人非小细胞肺癌(non-small-cell lung cancer,NSCLC)易感性的关系.方法 采用病例-对照研究,用聚合酶链反应-限制性片段长度多态性和DNA测序法检测福建籍汉族健康人258名和NSCLC患者260例的IGF-IR +1013和IGF-2R+1619两个位点的等位基因分布,探讨不同基因型与NSCLC发病的相关性.结果 (1) IGF-1R +1013(G/A)位点基因型和各等位基因的频率在两组中分布差异有统计学意义(P＜0.05).对于IGF-1R+ 1013(G/A)位点,与GG基因型者相比,GA基因型者NSCLC患病风险增加0.80倍(95％ CI:1.24～2.59,P=0.002),AA基因型者的风险增加2.59倍(95％ CI:1.78～7.26,P=0.000),而等位基因A携带者(GA+AA基因型)患病风险增加0.98倍(95％ CI:1.39～2.83,P=0.000).未发现IGF-2R +1619(G/A)位点各基因型和等位基因的频率分布在两组中差异有统计学意义(P＞0.05).(2)根据病理类型分层分析发现IGF-1R +1013(G/A)变异等位基因A携带者(GA+AA)患肺鳞癌的风险增加2.20倍(95％ CI:1.75～5.84,P=0.000),患肺腺癌的风险增加0.55倍(95％Ch l.00～2.41,P=0.049),患其他类型肺癌的风险增加0.96倍(95％CI:1.10～3.49,P=0.023).未发现两基因多态性与临床分期、淋巴结转移、远处转移有关(P＞0.05).(3)联合分析发现,IGF-1R+1013(G/A)和IGF-2R +1619(G/A)基因联合多态性与NSCLC的患病风险存在相关性(P=0.003).结论 IGF-IR+ 1013(G/A)位点变异等位基因A是肺癌发生的风险因素,IGF-1R+1013(G/A)和IGF-2R+1619(G/A)基因多态性对肺癌的发生有协同作用.     

乙型肝炎病毒增强子Ⅰ/X基因启动子变异与HBV慢性感染疾病谱的关系

目的 探讨乙型肝炎病毒增强子Ⅰ (HBV Enh Ⅰ)/X基因启动子变异与乙型肝炎病毒慢性化感染疾病谱的关系.方法 随机收集275例HBV感染者的血清标本,包括慢性乙型肝炎( CHB) 100例,肝硬化(LC)74例,肝细胞癌(HCC) 101例.以入选病例的基因型为分组,采用半巢式PCR的方法扩增HBV Enh Ⅰ/X基因启动子并测序,测序结果与HBV参照序列比对,确定变异位点,使用x2检验和多变量logistic回归进行数据分析.结果 ①HBV基因分型结果:HBV B基因型患者158例(61.48％),包括CHB 70例,LC 36例,HCC 52例;HBV C基因型患者117例(38.52％),包括CHB 30例,LC 38例,HCC 49例.②HBV B基因型A1123Y变异在LC组明显高于CHB组(30.56％vs.8.58％,x2=8.533,P=0.005,A=4.693,95％ CI[1.567～14.056]),HCC组明显高于CHB组(28.85％ vs.8.58％,x2 =8.607,P=0.003,OR=4.324,95％ CI[1.544 ～ 12.109]);A1317G变异在HCC组明显高于CHB组(30.77％ vs.7.14％,x2=11.687,P=0.001,A=5.778,95％ CI[1.955～17.076]).HBV C基因型T1323C变异在HCC组明显高于CHB组(30.61％ vs.6.67％,x2 =6.318,P=0.012,A=6.176,95％ CI[1.301～29.331]).③多变量logistic回归分析发现A1317G(A =5.706,95％ CI[1.770 ～ 18.837],P =0.004)和T1323C (A =5.810,95％ CI[1.114 ～30.306],P =0.037)变异是HCC发生的独立危险因素.结论 乙型肝炎病毒增强子Ⅰ/x基因启动子突变与肝硬化、肝癌的发生有关,对变异位点的检测有助于预测肝硬化和肝癌的发生.     

基于癌症基因图集数据库与免疫组织化学方法分析SMARCB1对肝细胞癌早期诊断及预后的作用

目的:通过研究SMARCB1在肝细胞癌(hepatocellular carcinoma,HCC)组织的表达,阐明其对HCC的早期诊断及预后的作用。方法:在癌症基因组图集(The Cancer Genome Atlas,TCGA)数据库中筛选出SMARCB1基因,运用免疫组织化学(immunohistochemistry,IHC)技术和TCGA分析SMARCB1在HCC组织和正常组织的表达情况,阐述其在HCC发生、发展进程中的作用。结果:IHC结果证实,与正常肝组织相比,HCC中SMARCB1的蛋白表达量显著上升(P0.01)。IHC的结果显示SMARCB1的蛋白表达量与原发肿瘤分期呈正相关(P0.05),即SMARCB1表达量越高,原发肿瘤分期越趋向晚期。TCGA的结果显示SMARCB1的高表达是HCC的独立预后因素(P0.05)。结论:SMARCB1可能起着促癌基因的作用,临床上根据其在组织中的表达差异,可鉴别早期的HCC及良性组织,并可能有效地进行预后判断。     

肝细胞癌患者血清外泌体中 PD-L1 的表达及其临床意义

目的 探究肝细胞癌 ( hepatocellular carcinoma, HCC) 患者血清外泌体中程序性死亡配体-1 (programmed death ligand 1, PD-L1) 的表达水平及临床意义。 方法 采用 ExoQuick 试剂盒提取 75 例 HCC 患者和 15 名健康对照者血清样本中的外泌体, 分别利用透射电镜、 NanoSight 以及 Western 印迹对其进行鉴 定; 采用 RT-qPCR 检测血清外泌体中 PD-L1 mRNA 的表达差异; 采用卡方检验分析血清外泌体 PD-L1 mRNA 表达水平与患者临床病理学特征的关系; 采用 Kaplan-Meier 法结合 Cox 回归分析探究血清外泌体 PD-L1 mRNA 表达的预后价值。 结果 透射电镜和 NanoSight 结果显示 HCC 患者和健康对照者血清中的外泌体粒 径主要集中 100 nm 左右, Western 印迹检测可见外泌体均表达 CD9 和 TSG101 标志蛋白, 而不表达细胞骨 架蛋白 Calnexin。 RT-qPCR 检测结果显示, HCC 患者血清外泌体中 PD-L1 mRNA 的表达水平明显高于健康 对照者 (t = 11. 670, P< 0. 001), 其高表达与肿瘤直径、 肿瘤数目、 Child-Pugh 分级、 AFP 水平以及门静脉 癌栓有关 (P均 < 0. 05)。 Kaplan-Meier 生存分析显示, 血清外泌体 PD-L1 mRNA 高表达组 HCC 患者的总生 存期较低表达组明显缩短 (P = 0. 004)。 单因素和多因素 Cox 回归分析表明, 血清外泌体 PD-L1 mRNA 高 表达是 HCC 患者总生存期缩短的独立危险因素 (HR = 2. 013, 95 % CI: 1. 012 ~ 3. 669, P = 0. 015)。 结论 HCC 患者血清外泌体中 PD-L1 表达明显上调, 且与肿瘤的恶性进展和不良预后密切相关, 具有成为 HCC 预后标志物的巨大潜力。     

原发性肝癌组织MicroRNA-497表达及与患者临床特征和生存率的关系

目的:回顾性分析microRNA-497(miRNA-497)在原发性肝癌(HCC)患者癌组织中的表达及与患者临床特征和生存率的关系。方法:收集2010-01—2010-10接受手术治疗的61例HCC患者,采用荧光定量PCR检测其癌组织及癌旁组织miRNA-497的相对表达量。以癌组织miRNA-497相对表达水平的中位数为界限,将61例患者分为miRNA-497高表达组(n=21)和miRNA-497低表达组(n=40)。比较癌组织与癌旁组织miRNA-497水平差异;同时分析miRNA-497高表达组与miRNA-497低表达组临床特征和预后危险因素;比较两组平均生存率和累计生存率的差异。结果:miRNA-497在癌组织中的表达明显低于癌旁组织,差异有统计学意义(P0.05)。HCC患者癌组织miRNA-497低表达组血清AFP水平、肿瘤大小、TNM分期、血管侵犯与高表达组分布差异有统计学意义(P0.05)。多因素回归分析显示血管侵犯、TNM分期、miRNA-497表达量是影响HCC患者预后的独立危险因素。Kaplan-Meier分析表明,miRNA-497低表达组平均生存期明显低于高表达组(19.0个月vs 33.3个月),1年、3年、5年累计生存率也较miRNA-497高表达组明显降低(55.0%vs 71.4%、20.0%vs 42.9%、15.0%vs 37.5%,P0.05)。结论:miRNA-497在HCC组织中的低表达提示预后不良。     

CEP55蛋白在原发性肝细胞癌组织中的表达与临床特征及预后的相关性分析

目的 分析中心体蛋白55(CEP55)在肝细胞癌(HCC)组织中的表达与临床特征及预后的相关性,为揭示肝癌诊断和治疗的新目标和策略提供依据.方法 基于TCGA-LIHC数据库分析CEP55在HCC和相应的正常组织中的表达差异,并进一步分析其与生存预后的关系.纳入185例于2015年4月至2016年7月在我院肝胆外科完成了肝切除术的HCC患者,对手术切除的肿瘤组织和癌旁组织(距离肿瘤边缘>5.0cm)制作组织蜡块.采用免疫组织化学染色法检测组织CEP55蛋白表达,分析CEP55表达与HCC患者不同临床特征的关系.采用Kaplan-Meier法绘制生存曲线,并使用Log-rank分析CEP55表达与预后的相关性.采用Logistic回归模型分析影响原发性肝癌患者预后的危险因素.结果 基于TCGA-LIHC数据库,418例肝癌组织中CEP55基因拷贝数明显高于癌旁正常组织(P<0.05),且根据每组CEP55表达水平的中位数值将患者分为两组.与LIHC队列中的低表达组相比,CEP55高表达组的总生存期(OS)和无进展生存期(PFS)明显缩短(Log-Rank检验,P<0.05).CEP55蛋白的表达与患者血管有无浸润、肿瘤直径、BCLC分期、T分期、N分期、分化程度、AFP水平有关(P<0.05).随访5年,CEP55蛋白高表达组和低表达组患者5年OS分别为64.9％(63/97)、84.0％(74/88)(Log-Rankχ2=10.192,P=0.001);5年PFS分别为54.6％(53/97)、69.3％(61/88)(Log-Rankχ2=5.750,P=0.016).经单因素和多因素Logistic回归分析,肿瘤组织CEP55高表达是影响患者预后的独立危险因素之一(P<0.05).结论 CEP55蛋白在HCC组织中普遍呈高表达,其与患者预后不良有关,可作为肝癌早期诊断或潜在治疗靶点的分子生物学指标.     

Upregulation of Heat Shock Proteins (HSPA12A,HSP90B1, HSPA4, HSPA5 and HSPA6) in Tumour Tissues Is Associated with Poor Outcomes from HBV-Related Early-Stage Hepatocellular Carcinoma

Background: Heat shock proteins (HSPs) are overexpressed in human hepatocellular carcinoma (HCC) tissue and correlate with aggressiveness and prognosis of HCC.Methods: Using the {"type":"entrez-geo","attrs":{"text":"GSE14520","term_id":"14520"}}GSE14520 microarray expression profile from Gene Expression Omnibus, we compared HSP gene expression between tumour and non-tumour tissues and correlated this with outcomes in HCC patients.Results: We analysed 220 hepatitis B virus (HBV)-related HCC patients and 25 HSPs in this study. With the exception of HSPA4L, HSPA12A and HSPB8, members of the HSP family, including HSPH1, HSPBP1, HSPA1A, HSPA1B, HSPA1L, HSPA2, HSPA4, HSPA5, HSPA8, HSPA9, HSPAA1, HSPAB1, HSPA14, HSPB11, HSPA13, HSP90B1 and HSPBAP1, were all overexpressed in tumour tissues (all P < 0.001). In contrast, HSPB6, HSPB7, HSPA6, HSPB2 and HSPB3 were upregulated in non-tumour tissues (all P < 0.001). Multivariate analysis showed that cirrhosis (HR = 5.282, 95% CI = 1.294-21.555, P = 0.02), Barcelona Clinic liver cancer (BCLC) staging (HR = 2.151, 95% CI = 1.682-2.750, P < 0.001), HSPA12A (HR = 1.042, 95% CI = 1.003-1.082, P = 0.033) and HSP90B1 (HR = 1.001, 95% CI = 1.000-1.001, P = 0.011) were negatively associated with survival of HBV-related HCC patients. Furthermore, advanced BCLC staging (HR = 1.797, 95% CI = 1.439-2.244, P < 0.001) was also associated with earlier recurrence of HCC. The high expression of HSPA4 (HR = 1.002, 95% CI = 1.000-1.004, P = 0.019), HSPA5 (HR = 1.0, 95% CI = 1.0-1.0, P = 0.046) and HSPA6 (HR = 1.008, 95% CI = 1.001-1.015, P = 0.021) was similarly associated with HCC recurrence.Conclusions: The expression of most HSPs was higher in tumour tissues than in non-tumour tissues. High BCLC staging scores, advanced cirrhosis and the overexpression of HSPA12A and HSP90B1 might be associated with poor survival from HCC, whereas high levels of HSPA4, HSPA5 and HSPA6 might be associated with earlier recurrence of HCC.     

Clinicopathologic and prognostic significance of p21 (Cip1/Waf1) expression in bladder cancer

Recent studies have shown that altered expression p21 is shown to associate with tumorigenesis and tumor progression. To investigate the clinicopathological significance and prognostic value of p21 in bladder cancer (BCa). A total of 48 patients with BCa were included in this study. The correlation between p21 expression and clinicopathologic features and survival was studied. Also, a meta-analysis was performed to investigate the relationship between the p21 and BCa survival. Low p21 expression was detected both in tumor tissues compared with adjacent normal tissues. The expression of p21 was closely associated with advanced pathologic TNM stage (P = 0.001) and tumor grade (P = 0.013). Moreover, patients with low p21 expression had shorter recurrence-free survival (P = 0.016) and overall survival rates (P = 0.039). Multivariate Cox regression analysis revealed that p21 low expression was an independent prognostic factor for recurrence free survival (P = 0.03). Additionally, our meta-analysis. The available outcome data from six articles were examined. A meta-analysis of the HR indicated a significantly poor overall survival (OS, HR: 1.75, 95% CI: 1.38-2.21), recurrence free survival (RFS, HR: 1.83, 95% CI: 1.57-2.15), progression free survival (PFS, HR: 2.02, 95% CI: 1.48-2.75), and cancer specific survival (CSS, HR: 1.89, 95% CI: 1.53-2.33) in patients with low expression levels of p21. Our present results indicated that low p21 expression predicated tumor recurrence and poor prognosis in bladder cancer.     

Expression of protein TARBP1 in human hepatocellular carcinoma and its prognostic significance

Objective: The objective of this study was to analyze the expression of TARBP1 and its clinical significance in hepatocellular carcinoma (HCC). Materials and Methods: 90 patients with primary hepatocellular carcinoma were included in this study. The tumor and paired adjacent non-tumor tissues were collected. TARBP1 expression was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry. Associations of TARBP1 expression with the clinicopathological features were analyzed, and prognosis of HCC patients was evaluated. Results: The result show the expression of TARBP1 mRNA in liver cancer tissues were higher than in the adjacent normal liver tissues in 10 paired samples (P=0.0015). Compared with adjacent normal liver tissues, overexpression of TARBP1 was detected in 61.1% (55/90) HCC patients. TARBP1 expression was associated with the AJCC tumor stage (P=0.004) and clinical stage (P=0.005), and decreased overall survival (P=0.002). In multivariate analysis, TARBP1 expression was an independent prognostic factor for overall survival (Hazard ratio [HR]=2.773, 95% confidence interval [CI] 1.542-4.985; P=0.019). Conclusions: TARBP1 is up-regulated in HCC, and the expression of TARBP1 was associated with the pathological grading and clinical stage. TARBP1 maybe is an independent prognostic marker of HCC patients.     

Elevated expression of UHRF1 predicts unfavorable prognosis for patients with hepatocellular carcinoma

Aims: The present study was designed to evaluate the different expression of ubiquitin-like with PHD and ring finger domains 1 (UHRF1) in hepatocellular carcinoma (HCC) tissues and the adjacent normal tissues, further explore the correlation between UHRF1 expression and the prognosis of HCC patients. Methods: The UHRF1 expression at protein level in HCC tissues and the adjacent normal tissues were measured by high performance liquid chromatography (HPLC). Chi-square test was used to estimate the relationship between UHRF1 expression and clinicopathologic characteristics of HCC patients. The overall survival of HCC patients with diverse expression of UHRF1 was measured by Kaplan-Meier analysis. Cox regression analysis was conducted to judge the prognostic value of UHRF1 in HCC patients. Results: The UHRF1 was over-expressed in HCC tissues compared with the adjacent normal tissues according to the outcome of HPLC (P<0.001). Besides, the UHRF1 expression was tightly related to distant metastasis, cancer area, and HBV (P<0.05), but shared no correlation with gender, cirrhosis, and bilirubin (P>0.05). Patients with high UHRF1 expression had a shorter overall survival time than those with low UHRF1 expression (P<0.001). Cox regression analysis showed that UHRF1 was significantly linked with the prognosis of HCC patients (P=0.002, HR=5.807, 95% CI=1.901-17.742). Conclusion: UHRF1 was over-expressed in HCC tissues compared to the adjacent normal tissues and UHRF1 expression shared significant relevance with distant metastasis, cancer area and HBV. It could be an important and independent prognostic biomarker for HCC patients.     

Overexpression of FZD7 is associated with poor survival in patients with colon cancer

BackgroundOverexpression of Frizzled-7 (FZD7) has been associated with tumor invasion and distant metastases, but little is known about the relationship between FZD7 expression and prognosis in colon cancer.Patients and methodsA total of 114 patients with colon cancer between June 2010 and December 2010 were enrolled in this study. The expression of FZD7 in cancerous and adjacent non-cancerous tissues was determined by immunohistochemistry, and the association between FZD7 expression and patient’s clinicopathological characteristics was explored. The correlation between FZD7 expression and prognosis of colon cancer patients was analyzed using the Oncomine database and R2.ResultsFZD7 expression levels were significantly higher in colon cancer tissues compared with adjacent non-cancerous tissues (P < 0.001). High expression of FZD7 was significantly associated with metastatic or recurrent disease in colon cancer (P = 0.010). Kaplan-Meier survival analysis demonstrated that colon cancer patients with high expression of FZD7 had a significantly poorer OS (P = 0.013) and DFS (P = 0.010). Cox regression demonstrated that the expression of FZD7 was an independent prognostic factor for DFS (HR = 6.647, P = 0.023). A meta-analysis from the Oncomine database demonstrated that FZD7 mRNA levels were significantly higher in colorectal cancer tissues than in normal colorectal tissues, and FZD7 high expression was associated with a significantly poorer event and relapse-free survival time by analyzing the data from the R2: Genomics Analysis and Visualization Platform.ConclusionsOverexpression of FZD7 was associated with poor survival in patients with colon cancer. Our data suggest that FZD7 expression could be an effective prognostic biomarker for colon cancer.     

Insulin-like growth factor receptor 1 (IGF1R) expression and survival in non-small cell lung cancer patients: a meta-analysis

The insulin-like growth factor receptor-1 (IGF1R) plays an important role in cancer progression. Previous studies have been controversial with respect to the associations between IGF1R expression and non small cell lung cancer (NSCLC) prognosis. Thus, we performed a meta-analysis to investigate the prognostic value of IGF1R expression in NSCLC patients and the relationship between the expression of IGF1R and clinical characteristics. Two independent reviewers searched PubMed, Embase, Ovid Medline and CNKI to identify eligible studies. Overall survival (OS), disease free survival (DFS) and clinicopathological characteristics were collected from included studies. Pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence interval (95% CI) were calculated to estimate the effect. 17 studies comprising 3,294 patients were included in this meta-analysis. The results showed IGF1R positive expression was associated with an unfavorable DFS in NSCLC patients on univariate analysis (HR = 1.26, 95% CI: 1.09-1.46, P = 0.002) and multivariate analysis (HR = 1.49, 95% CI: 1.01-2.20, p = 0.045), but the relationship between IGF1R expression and OS have no significant difference on univariate analysis (HR = 0.91, 95% CI: 0.82-1.01, P = 0.157) and multivariate analysis (HR = 0.79, 95% CI: 0.45-1.41, P = 0.427). Ever smoking and smaller tumor size (T1 or T2) were associated with IGF1R positive expression: pooled OR 1.45 (1.13-1.85) and pooled OR 0.61 (0.60-0.95). Our results suggested IGF1R positive expression as an unfavorable factor for DFS in NSCLC patients, and IGF1R expression was associated with smoking status and tumor size.     

SCNM1在乙肝相关性肝癌中的表达及临床意义

目的:研究钠离子通道调节蛋白1(SCNM1)在乙肝相关性肝癌中的表达情况,并探讨其表达差异与临床病理特征及预后的关系。方法:标本来源于2013年1月～2015年12月在中山大学附属第三医院接收治疗的108例乙肝相关性肝癌患者,所有患者均签署知情同意书,符合医学伦理学规定。结合公共数据库中的肝癌资料,分析SCNM1的m RNA表达水平;应用RT-qPCR检测乙肝相关性肝癌组织及癌旁组织中SCNM1的m RNA表达水平,并分析SCNM1的表达水平与乙肝相关性肝癌临床病理特征的关系;利用Kaplan-Meier plotter分析SCNM1与肝癌患者预后的相关性。结果:TCGA数据库、Human Protein Atlas数据库和Oncomine数据库的分析结果显示,SCNM1在肝癌组织中的表达量明显高于正常肝组织(P 0. 01)。SCNM1主要分布于细胞核中。RT-qPCR检测结果显示,乙肝相关性肝癌组织中SCNM1的m RNA中位表达水平明显高于其配对癌旁组织(t=8. 082,P 0. 01)。乙肝相关性肝癌患者中SCNM1的表达水平与肝硬化、丙氨酸转氨酶和肿瘤大小具有相关性(P 0. 05),而与患者的性别、年龄和肿瘤包膜等临床病理特征无相关,SCNM1高表达的肝癌患者总生存时间较低表的患者达短(HR=1. 53,P=0. 016),SCNM1高表达的乙肝相关性肝癌患者总生存时间更短(HR=2. 41,P=0. 015)。结论:在乙肝相关性肝癌中,SCNM1高表达并且和患者的预后相关。SCNM1在乙肝相关性肝癌的发生中可能起着重要作用。     

Up-regulation of long non-coding RNA CCAT2 correlates with tumor metastasis and poor prognosis in cervical squamous cell cancer patients

Background: Dysregulation of long non-coding RNAs (lncRNAs) plays critical roles in tumor progression. The purpose of this study was to investigate the relationship between lncRNA CCAT2 expression and cervical squamous cell cancer susceptibility and prognosis. Methods: Expression levels of lncRNA CCAT2 in 123 cervical squamous cell tumor specimens were determined by quantitative real-time PCR (qRT-PCR), to clarify the clinical significance of lncRNA CCAT2 in cervical squamous cell cancer, we further discussed the relationship between lncRNA CCAT2 expression and overall survival (OS) and progression-free survival (PFS). Results: In the present study, we found that lncRNA CCAT2 was up-regulated in cervical squamous cell cancer tissues compared to the adjacent non-tumor tissues. In addition, the high lncRNA CCAT2 expression was significantly associated with the FIGO stage, lymph node metastasis and depth of cervical invasion (P<0.05). Furthermore, patients with high expression of lncRNA CCAT2 had poor OS (HR=2.813, 95% CI: 1.504-6.172; P=0.017), and PFS rates (HR=3.072, 95% CI: 1.716-8.174; P=0.008). Multivariate Cox proportional hazard model analysis demonstrated that high lncRNA CCAT2 expression was an independent poor prognostic factor for cervical squamous cell cancer patients. Conclusions: Our study suggested that high expression of lncRNA CCAT2 is related to the prognosis of cervical squamous cell cancer; it may be a new prognostic biomarker and potential therapeutic target for cervical squamous cell cancer intervention.     

Clinical significance and prognostic value of Nek2 protein expression in colon cancer

Objective: To determine the expression of NIMA-related kinase NEK2 and evaluate its clinical value in colon cancer. Method: Sixty specimens of colon cancer, 30 specimens of paracancerous colon tissues and 10 specimens of normal colon tissues conventionally resected in surgery at the Second Affiliated Hospital of Nantong University from February 2006 to February 2014 were collected. These tissues were detected for the expression of Nek2 using Western Blot and immunohistochemical staining. The relationship between Nek2 protein expression and the clinicopathology and prognosis of colon tissues was discussed. Results: The expression level and positive expression rate of Nek2 protein in the colon cancer were obviously higher than that in the paracancerous tissues and normal colon tissues. They were also significantly higher in the paracancerous tissues than in the normal tissues (P<0.05). Statistical analysis revealed that Nek2 protein expression was not obviously correlated with gender, age and tumor size, but obviously correlated with degree of differentiation (P=0.008), TNM staging (P=0.000), lymph node metastasis (P=0.022) and tumor invasion (P=0.011). With the plotting of Kaplan-Meier survival curve, it could be seen that Nek2 protein expression was not significantly correlated with survival (P=0.0048). High Nek2 protein expression may be an independent risk factor for colon cancer (HR=0.227, 95% CI 0.101-0.510). Conclusion: High Nek2 protein expression reflects the malignant behavior of colon cancer. Playing important roles in the occurrence of colon cancer, Nek2 protein expression has diagnostic and prognostic value in colon cancer.