胰腺癌患者循环肿瘤细胞及TLR4、TLR9、myd88的表达水平与其化疗效果及转移、复发的关系

目的:探讨胰腺癌患者循环肿瘤细胞(CTC)中Toll样受体4(TLR4)、Toll样受体9(TLR9)、髓样分化因子88(myd88)的表达水平与患者化疗效果及转移、复发的关系。方法:将我院2015年6月-2016年6月收治并确诊的48例胰腺癌患者作为试验组,收集患者循环肿瘤细胞(CTC),检测其TLR4、TLR9、myd88信号表达情况,探讨其TLR4、TLR9、myd88信号表达水平与患者化疗效果及转移、复发的关系。结果:48例胰腺癌患者检出CTC 35例,检出率为72.9%。胰腺癌死亡、转移、复发患者TLR4、TLR9、myd88表达水平分别高于其存活、未转移、未复发患者,组间具有统计学差异(P0.05)。胰腺癌化疗效果CR患者TLR4、TLR9、myd88表达水平显著低于其化疗效果PR、SD、PD患者,且四组间差异具有统计学意义(P0.05);TLR4、TLR9、myd88表达水平与被膜受侵犯、淋巴结转移、肿瘤大小、CA199水平呈正相关(P0.05)。结论:胰腺癌患者CTC中TLRs/myd88信号表达水平与患者化疗效果及转移、复发密切相关。     

Tim-3 Expression in Cervical Cancer Promotes Tumor Metastasis

BackgroundT cell immunoglobulin mucin-3 (Tim-3) has been identified as a negative regulator of anti-tumor immunity. Recent studies highlight the important role of Tim-3 in the CD8⁺ T cell exhaustion that takes place in both human and animal cancer models. However, the nature of Tim-3 expression in the tumor cell and the mechanism by which it inhibits anti-tumor immunity are unclear. This present study aims to determine Tim-3 is expressed in cervical cancer cells and to evaluate the role of Tim-3 in cervical cancer progression.MethodologyA total of 85 cervical tissue specimens including 43 human cervical cancer, 22 cervical intraepithelial neoplasia (CIN) and 20 chronic cervicitis were involved. Tim-3 expression in tumor cells was detected and was found to correlate with clinicopathological parameters. Meanwhile, expression of Tim-3 was assessed by RT-PCR, Western Blot and confocal microscopy in cervical cancer cell lines, HeLa and SiHa. The migration and invasion potential of Hela cells was evaluated after inhibiting Tim-3 expression by ADV-antisense Tim-3.ConclusionsWe found that Tim-3 was expressed at a higher level in the clinical cervical cancer cells compared to the CIN and chronic cervicitis controls. We supported this finding by confirming the presence of Tim-3 mRNA and protein in the cervical cell lines. Tim-3 expression in tumor cells correlated with clinicopathological parameters. Patients with high expression of Tim-3 had a significant metastatic potential, advanced cancer grades and shorter overall survival than those with lower expression. Multivariate analysis showed that Tim-3 expression was an independent factor for predicting the prognosis of cervical cancer. Significantly, down-regulating the expression of Tim-3 protein inhibited migration and invasion of Hela cells. Our study suggests that the expression of Tim-3 in tumor cells may be an independent prognostic factor for patients with cervical cancer. Moreover, Tim-3 expression may promote metastatic potential in cervical cancers.     

MTA1 promotes the invasion and migration of pancreatic cancer cells potentially through the HIF-α/VEGF pathway

Abstract

The metastasis-associated gene 1 (MTA1) has previously been recognized as an oncogene, and abnormal MTA1 expression has been related to progression of numerous cancer types to the metastasis stage. However, the function of MTA1 in the regulation of pancreatic cancer progression and metastasis remains unclear. Western blot analysis was adopted to determine the expression of MTA1 in pancreatic cancer tissues and corresponding near normal tissues. Steady clone with MTA1-overexpression and MTA1-inhibitionweregenerated via lentivirus technology in BxPc-3 cells. Transwell assay was carried out for detecting the invasion of pancreatic cancer cells. The migration activity was assessed using the wound scratch assay. The effect of MTA1 in pancreatic cancer was evaluated in the mice xenografts. Western blot analysis was employed to determine the expression of hypoxia inducible factor-α (HIF-α) and vascular endothelial growth factor (VEGF) in vitro and in vivo. We observed that MTA1 overexpression enhanced migration and invasion ability of pancreatic cancer cells in vitro and increased HIF-α and VEGF protein levels in vitro and in vivo. MTA1 inhibition had the opposite effects. MTA1 protein level was positively related to HIF-α and VEGF protein levels. These results indicated that MTA1 potentially promoted pancreatic cancer metastasis via HIF-α/VEGF pathway. This research supplies a new molecular mechanism for MTA1 in the pancreatic cancer progression and metastasis. MTA1 may be an effective therapy target in pancreatic cancer.     

腹腔镜与开腹胰十二指肠切除术治疗胰头癌的疗效对比及术后肿瘤早期复发的随访研究

摘要 目的：对比腹腔镜与开腹胰十二指肠切除术治疗胰头癌的疗效,并分析术后肿瘤早期复发的影响因素。方法：选择2019年3月~2020年4月期间四川大学华西空港医院普外科收治的15例及四川大学华西医院胰腺外科收治的65例共计80例胰头癌患者,根据手术方式的不同分为开腹组和微创组,例数分别为32例和48例,对比两组围术期相关临床指标、并发症发生率和随访期间的肿瘤早期复发率。采用多因素Logistic回归分析术后早期复发的影响因素。结果：微创组的手术时间长于开腹组,住院费用多于开腹组,术中出血量少于开腹组,下床活动时间、术后排气时间、开始进食时间、术后住院时间短于开腹组（P<0.05）。两组并发症发生率对比无差异（P>0.05）。两组术后肿瘤早期复发率对比差异无统计学意义（P>0.05）。单因素分析结果显示,胰头癌患者术后肿瘤早期复发与年龄、肿瘤最大直径、有无淋巴结转移、有无脉管癌栓、有无神经侵犯、术前白蛋白、术前糖类抗原125（CA125）、术前癌胚抗原（CEA）水平、术后有无放化疗有关（P<0.05）。多因素Logistic回归分析显示：淋巴结转移、脉管癌栓、神经侵犯、术后未放化疗以及术前CA125水平较高是胰头癌患者术后肿瘤早期复发的危险因素（P<0.05）。结论：相较于传统开腹手术,腹腔镜下行胰十二指肠切除术治疗胰头癌,可缩短住院时间,促进患者术后恢复,但两者间并发症发生率和术后早期复发率无显著差异。胰头癌术后肿瘤早期复发受到淋巴结转移、脉管癌栓、神经侵犯、术后放化疗、术前CA125水平等多种因素的影响。     

Decreased Galectin-9 and Increased Tim-3 Expression Are Related to Poor Prognosis in Gastric Cancer

Introduction

Galectin-9 (Gal-9) induces adhesion and aggregation of certain cell types and inhibits the metastasis of tumor cells. T-cell immunoglobulin–and mucin domain-3–containing molecule 3 (TIM-3) plays a pivotal role in immune regulation. The aim of this study is to investigate Gal-9 and TIM-3 alterations in gastric cancer and their prognostic values.

Methods

Gal-9 and Tim-3 expression was evaluated using a tissue microarray immunohistochemistry method in 305 gastric cancers, of which 84 had paired adjacent normal samples. Cell lines SGC-7901, BGC-823, MGC-803, MKN45 and GES-1 were also stained. Correlations were analyzed between expression levels of Gal-9 and Tim-3 protein and tumor parameters or clinical outcomes.

Results

Gal-9 and Tim-3 stained positive on tumor cells in 86.2% (263/305), and 60.0% (183/305) patients with gastric cancer, respectively. Gal-9 expression was significantly higher in cancer than in normal mucosa (P<0.001). Reduced Gal-9 expression was associated with lymph-vascular invasion, lymph node metastasis, distant metastasis and worse TNM staging (P = 0.034, P = 0.009, P = 0.002 and P = 0.043, respectively). In contrast, Tim-3 expression was significantly lower in cancer than in control mucosa (P<0.001). Patients with lymph-vascular invasion had higher expression levels of Tim-3 (P<0.001). Moreover, multivariate analysis shows that both high Gal-9 expression and low Tim-3 expression were significantly associated with long overall survival (P = 0.002, P = 0.010, respectively); the combination of Gal-9 and Tim-3 expression was an independent prognostic predictor for patients with gastric cancer (RR: 0.43; 95%CI: 0.20–0.93). H.pylori infection status was not associated with Gal-9 and Tim-3 expression (P = 0.102, P = 0.565).

Conclusion

The results suggest that expression of Gal-9 and Tim-3 in tumor cells may be a potential, independent prognostic factor for patients with gastric cancer. Gal-9 and TIM-3 may play an important part in the gastric carcinogenesis.     

氨基酸转运载体ASCT2和LAT1在胃癌组织的表达及其临床价值

摘要 目的：研究ASC型氨基酸转运体2（ASCT2）和L型氨基酸转运体1（LAT1）在胃癌组织中的表达情况,并探讨其临床价值。方法：收集70例进展期胃癌组织以及相对应的肿瘤旁组织,采用免疫组化方法检测ASCT2和LAT1在相应组织中的表达水平,并研究其表达与患者临床病理参数和预后的相关性。结果：与癌旁组织相比,胃癌组织中ASCT2或LAT1的高表达率均有统计学差异,但其各自的表达率与癌旁组织相比无明显差异。LAT1和ASCT2在胃癌组织中的共表达率与癌旁组织相比有明显统计学差异。胃癌组织中ASCT2高表达与肿瘤体积、T分期、N分期、TNM分期和Ki-67指数显著相关;LAT1的高表达与肿瘤体积、N分期和TNM分期相关。胃癌组织中ASCT2与LAT1共表达与肿瘤体积、T分期、N分期、TNM分期和Ki-67指数显著相关。胃癌组织中ASCT2和LAT1的高表达呈正相关。胃癌组织中ASCT2高表达、LAT1高表达及ASCT2与LAT1共表达与患者不良预后有关。结论：胃癌组织中ASCT2高表达、LAT1高表达以及ASCT2与LAT1共表达提示患者预后不良,有一定临床价值。     

MicroRNA-21在卵巢癌病灶转移过程中的作用及机制研究

目的:探讨micro RNA-21在卵巢癌病灶转移过程中的作用及其机制。方法:选取本院2016年6月-2018年5月收治的138例卵巢癌患者,其中63例出现结直肠转移,75例未发现有转移。q RT-PCR分别检测两组患者肿瘤组织、癌旁组织和正常组织中micro RNA-21的表达;Western blot检测两组患者肿瘤组织中PGDH、PGE2、Twist表达。通过转染过表达载has-micro RNA-21上调A2780细胞中micro RNA-21的表达,采用平板克隆实验检测细胞克隆形成能力,Trans-well细胞迁移实验和侵袭实验分别检测细胞迁移和侵袭能力。Western blot检测PGDH、PGE2、Twist蛋白表达。结果:卵巢癌转移组肿瘤组织中micro RNA-21表达高于未转移组、癌旁组织和正常卵巢组织(P0.05),卵巢癌转移组肿瘤组织中PGDH表达低于未转移组,而PGE2、Twist表达高于未转移组(P0.05)。micro RNA-21过表达的A2780细胞平板克隆形成能力、迁移和侵袭能力及上皮间质转化相关蛋白PGE2和Twist表达均明显高于阴性对照组(P0.05),而PGDH表达的表达明显降低(P0.05)。结论:micro RNA-21可能通过抑制PGDH的表达增加PGE2的表达,进而激活上皮间质转化,促进卵巢癌转移。     

CD80、CD86在鼻咽癌中的表达及其临床病理意义

目的:研究CD80、CD86在鼻咽癌中的表达变化及其临床病理意义。方法:选择2014年10月至2018年10月本院接诊的鼻咽癌确诊患者64例纳入研究,依据鼻咽癌复发情况分复发组(n=30)和未复发组(n=34);同期选取正常鼻粘膜活检组织33例作为正常对照组,采用SP免疫组化法检测鼻咽癌患者癌组织或正常鼻粘膜活检组织CD80、CD86蛋白的表达,并经Spearman相关性分析法分析CD80、CD86蛋白表达与鼻咽癌恶化程度的相关性。结果:鼻咽癌的癌组织CD80、CD86蛋白均呈高表达,阳性表达主要定位于细胞膜、细胞质,与肿瘤临床TNM分期、淋巴结转移均显著相关(P0.05)。复发组、未复发组肿瘤组织中的mRNA(ARD1、Ptch1、Survivin)表达显著高于对照组,且复发组高于未复发组,差异有统计学意义(P0.05)。Spearman相关性分析显示CD80、CD86蛋白表达与鼻咽癌细胞侵袭能力呈显著正相关(r=0.403、0.547,P0.05)。结论:鼻咽癌的癌组织内CD80、CD86蛋白均呈高表达,与鼻咽癌的临床分期、淋巴结转移及放疗预后关系密切,可能作鼻咽癌临床诊治及预后评估的重要参考指标。     

microRNA-221在胃癌中的表达及临床意义

目的:研究microRNA-221及E-cadherin在胃癌组织中的表达及其临床意义。方法:选取哈尔滨医科大学附属四院2014年-2016年收治的的胃癌患者50例,分别取胃癌及癌旁正常组织作为研究组及对照组。分别应用实时荧光定量PCR及免疫组织化学方法检测其中microRNA-221及E-cadherin的表达。结果:micro RNA-221在胃癌组织中的表达较正常组织显著增高(P0.05),E-cadherin在胃癌组织中的阳性表达率较正常组织显著降低。胃癌组织中microRNA-221的表达与患者的TNM分期、淋巴结转移及远处转移具有显著相关性(P0.05),E-cadherin的表达与患者淋巴结转移及远处转移具有显著相关性(P0.05)。胃癌患者中E-cadherin阴性表达者microRNA-221的相对表达量明显高于E-cadherin阳性表达者(P0.05)。结论:microRNA-221在胃癌组织中呈高表达,E-cadherin在胃癌组织中呈低表达,二者在胃癌组织中的表达呈负相关。microRNA-221可能通过影响上皮细胞间充质转化影响胃癌的浸润与转移。     

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。     

泛素相关蛋白样因子2在肝癌中的表达及意义

目的:探讨肝癌中泛素相关蛋白样因子2(UBAP2L)的表达水平与预后的关系及其对肝癌细胞侵袭、转移能力的影响。方法:挖掘oncomine数据库,提取UBAP2L在肝癌与正常组织转录水平的变化及相关临床资料,采用Kaplan-Meier法分析UBAP2L表达水平与肝癌患者预后的关系。采用实时定量PCR、Western blot检测HCCLM3、MHCC97H、Hep3B、Huh7肝癌细胞株及正常肝细胞LO2中UBAP2L mRNA及蛋白水平,免疫组织化学染色法检测本院80例肝癌组织与癌旁组织中UBAP2L的表达水平加以验证。通过慢病毒载体使UBAP2L高表达的肝癌细胞株HCCLM3表达下调,采用克隆形成和划痕实验检测UBAP2L对肝癌细胞增殖能力和侵袭、转移的影响。结果:UBAP2L在oncomine数据库大多数队列呈高表达。UBAP2L在肝癌细胞株中的mRNA和蛋白的表达水平显著高于正常肝细胞(P0.05)。肝癌组织中UBAP2L阳性、强阳性表达率高于癌旁组织(P0.05),下调UBAP2L表达可明显抑制HCCLM3肝癌细胞的克隆形成能力和运动能力(P0.05)。UBAP2L高表达组的中位生存时间与UBAP2L低表达组比较差异无统计学意义(P0.05)。结论:UBAP2L在肝癌组织中呈高表达,下调UBAP2L表达可抑制肿瘤增殖和侵袭、转移表型,其可能成为肝癌早期诊断的生物标志物和治疗的潜在靶点。     

结直肠癌组织ANP32A、Ataxin-3、FHL1的表达及其与肝转移的关系研究

摘要 目的：探讨结直肠癌组织中酸性核磷蛋白32A（ANP32A）、Ataxin-3及4个半LIM结构域蛋白1（FHL1）的表达及其与肝转移的关系。方法：对120例结直肠癌患者癌组织和癌旁组织中ANP32A、Ataxin-3及FHL1蛋白水平进行检测,分析其阳性表达率。其中44例发生肝转移作为肝转移组,76例无肝转移作为无肝转移组,比较两组癌组织中ANP32A、Ataxin-3及FHL1蛋白阳性表达率,分析结直肠癌肝转移的影响因素,分析ANP32A、Ataxin-3、FHL1蛋白之间的相关性。结果：结直肠癌患者癌组织中ANP32A蛋白阳性表达率高于癌旁组织,Ataxin-3、FHL1蛋白阳性表达率低于癌旁组织（P<0.05）。经单因素分析显示肝转移组患者癌组织中ANP32A蛋白阳性表达率显著高于无肝转移组,Ataxin-3、FHL1蛋白阳性表达率显著低于无肝转移组（P<0.05）,肝转移组患者原发癌中低分化、原发癌浸润深度T3~T4、原发癌有淋巴结转移者构成比显著高于无肝转移组（P<0.05）。多因素Logistic回归分析显示,ANP32A蛋白阳性表达、原发癌中低分化、原发癌浸润深度T3~T4、原发癌有淋巴结转移是结直肠癌肝转移的危险因素（P<0.05）,Ataxin-3、FHL1蛋白阳性表达是结直肠癌肝转移的保护因素（P<0.05）。Spearman相关分析显示,结直肠癌患者癌组织中ANP32A阳性表达率与Ataxin-3、FHL1阳性表达率呈负相关（P<0.05）,Ataxin-3蛋白阳性表达率与FHL1蛋白阳性表达率呈正相关（P<0.05）。结论：ANP32A蛋白高表达,Ataxin-3、FHL1蛋白低表达与结直肠癌发生及肝转移有密切关系,且以上指标间具有一定相关性。结直肠癌肝转移受多种因素影响,临床诊治中可根据相关因素为患者制定针对性治疗方案。     

NAC-1在膀胱癌中的表达及其与血管生成的相关性研究

目的:检测NAC-1在膀胱癌及癌旁组织中的表达,及其与膀胱癌临床病理的相关性研究,并进一步探讨其与血管生成的关系,为阐明膀胱癌的发生发展机制提供基础。方法:采用免疫组化法检测88例膀胱癌和30例癌旁组织石蜡块中NAC-1的表达情况,用si-RNA干扰技术下调膀胱癌细胞系T-24中NAC-1的表达,然后通过q RT-PCR方法检测干扰组及对照组中促血管生成因子(VEGF、b FGF、EGFR)的表达。结果:膀胱癌组织和癌旁组织中NAC-1的阳性表达率分别为79.54%和13.33%,膀胱癌组织显著高于癌旁组织(P0.01);NAC-1表达与膀胱癌的肿瘤级别、肌肉浸润程度及淋巴结转移显著相关(P0.05),在高级别、肌肉浸润及淋巴结转移的膀胱癌中呈现高表达,细胞实验发现NAC-1下调能够抑制促血管生成因子(VEGF、b FGF、EGFR)的表达。结论:NAC-1作为肿瘤相关基因在膀胱癌中高表达,并与膀胱癌的临床病理密切相关,其能调节促血管生长因子,可能会在肿瘤的血管生成及转移中具有重要的作用。     

幽门螺杆菌感染性胃癌组织中cyclinD1、MMP-9的表达及其临床意义

目的:探讨幽门螺杆菌(HP)感染性胃癌组织中细胞周期蛋白D1(cyclinD1)、基质金属蛋白酶-9(MMP-9)的表达及其临床意义。方法:选取2016年12月到2018年6月期间在兰州大学第一医院接受治疗的胃癌患者80例,收集其手术切除的病理组织。采用C-14呼气试验和改良Giemsa染色检测患者HP感染的情况,采用免疫组化法检测胃癌组织中cyclinD1、MMP-9表达情况。分析HP感染、cyclinD1、MMP-9表达与胃癌患者临床病理特征的关系,并分析胃癌患者HP感染与cyclinD1、MMP-9表达的相关性。结果:80例胃癌患者HP感染阳性56例(70.00%),阴性24例(30.00%)。有淋巴结转移、浸润深度为T3+T4的胃癌患者的HP感染阳性率高于无淋巴结转移、浸润深度为T1+T2的胃癌患者(P0.05)。80例胃癌患者cyclinD1阳性表达45例(56.25%),阴性表达35例(43.75%),MMP-9阳性表达65例(81.25%),阴性表达15例(18.75%),TNM临床分期为III+IV期、分化程度为低分化、有淋巴结转移、浸润深度为T3+T4的胃癌患者的cyclinD1、MMP-9阳性表达率明显高于TNM临床分期为I+II期、分化程度为中高分化、无淋巴结转移、浸润深度为T1+T2的胃癌患者(P0.05)。HP感染阳性患者的cyclinD1阳性表达率和MMP-9阳性表达率均明显高于HP感染阴性患者(P0.05)。Pearson相关分析显示,胃癌患者HP感染与cyclinD1、MMP-9表达均呈正相关(P0.05)。结论:胃癌患者的HP感染情况与淋巴结转移、浸润深度有关,cyclinD1和MMP-9的表达与TNM临床分期、分化程度、淋巴结转移、浸润深度有关,且胃癌患者HP感染与cyclinD1、MMP-9表达均呈正相关。     

MiRNA-615-5p Functions as a Tumor Suppressor in Pancreatic Ductal Adenocarcinoma by Targeting AKT2

Background

Aberrant microRNA (miRNA) expression is associated with tumor development. This study aimed to elucidate the role of miR-615-5p in the development of pancreatic ductal adenocarcinoma (PDAC).

Methods

Locked nucleic acid in situ hybridization (LNA-ISH) was performed to compare miR-615-5p expression in patients between PDAC and matched adjacent normal tissues. Effects of miR-615-5p overexpression on cell proliferation, apoptosis, colony formation, migration, and invasion were determined in the pancreatic cancer cell lines PANC-1 and MIA PaCa-2. Effects of miR-615-5p on AKT2 were examined by dual-luciferase reporter assay. Lentivirus expressing miR-615 was used to create stable overexpression cell lines, which were subsequently used in mouse xenograft and metastasis models to assess tumor growth, apoptosis and metastasis.

Results

miR-615-5p expression was significantly lower in PDAC than in adjacent normal tissues. Low levels of miR-615-5p were independently associated with poor prognosis (HR: 2.243, 95% CI: 1.190-4.227, P=0.013). AKT2 protein expression was inversely correlated with miR-615-5p expression (r=-0.3, P=0.003). miR-615-5p directly targeted the 3’-untranslated region of AKT2 mRNA and repressed its expression. miR-615-5p overexpression inhibited pancreatic cancer cell proliferation, migration, and invasion in vitro, and tumor growth and metastasis in vivo. Furthermore, miR-615-5p overexpression also induced pancreatic cancer cell apoptosis both in vitro and in vivo.

Conclusions

These results show that miR-615-5p inhibits pancreatic cancer cell proliferation, migration, and invasion by targeting AKT2. The data implicate miR-615-5p in the prognosis and treatment of PDAC.     

肝细胞肝癌组织NTS、SPNS2、Mortalin表达与上皮间质转化标志物、临床病理特征和预后的关系

摘要 目的：探讨肝细胞癌（HCC）癌组织神经降压素（NTS）、鞘氨醇-1-磷酸转运体2（SPNS2）、热休克蛋白75（Mortalin）表达与上皮间质转化（EMT）标志物、临床病理特征和预后的关系。方法：选取2010年1月～2017年1月联勤保障部队第九〇〇医院仓山院区收治的90例HCC患者,采用免疫组化法检测患者癌组织和对应癌旁组织中NTS、SPNS2、Mortalin及EMT标志物N-钙粘蛋白（N-Cad）、E-钙粘蛋白（E-Cad）表达情况。分析NTS、SPNS2、Mortalin表达与HCC患者EMT标志物、临床病理特征和预后的关系。结果：HCC癌组织中NTS、SPNS2、Mortalin、N-Cad阳性表达率高于癌旁组织,E-Cad阳性表达率低于癌旁组织（P＜0.05）。Pearson相关性分析显示,HCC癌组织中NTS、SPNS2、Mortalin表达水平与N-Cad表达水平呈正相关,与E-Cad表达水平呈负相关（P＜0.05）。 HCC癌组织中NTS、SPNS2、Mortalin表达与Child-Pugh分级、血管侵犯、巴塞罗那临床肝癌（BCLC）分期、淋巴结转移、远处转移有关（P＜0.05）。90例HCC患者术后5年总生存率为48.89％（44/90）。Kaplan-Meier生存曲线分析显示,NTS、SPNS2、Mortalin阳性组总生存率分别低于NTS、SPNS2、Mortalin阴性组（P＜0.05）。结论：HCC癌组织中NTS、SPNS2、Mortalin表达上调,与EMT、Child-Pugh分级、血管侵犯、BCLC分期、淋巴结转移、远处转移和预后有关,可作为HCC病情及预后的辅助评估指标。     

宫颈癌组织RACK-1、Lgr5表达与临床病理特征及预后的关系

目的:探讨宫颈癌(CC)组织激活的蛋白激酶C受体1(RACK-1)、富含亮氨酸重复序列的G蛋白偶联受体5(Lgr5)表达与临床病理特征及预后的关系。方法:选取2012年1月-2016年1月于三峡大学附属仁和医院接受手术治疗的134例CC患者作为研究对象,选取CC组织以及对应的癌旁正常组织,同时选取该院因宫颈良性病变行肿物剥除或附件切除的134例患者的正常宫颈组织作为对照,采用免疫组化链霉素抗生物素蛋白-过氧化物酶连(SP)法对各组织进行免疫组化染色,依据阳性细胞率和染色强度分析CC组织中RACK-1、Lgr5的表达情况,并分析RACK-1、Lgr5表达与CC患者临床病理特征的相关性,分析Lgr5及RACK-1不同阳性表达强度的CC患者的预后。结果:CC组织中RACK-1、Lgr5阳性表达率高于癌旁组织和正常宫颈组织,差异有统计学意义(P0.05);RACK-1、Lgr5阳性表达与TNM分期、肿瘤分化程度、淋巴结转移、脉管内癌栓相关(P0.05),与患者的年龄、肿瘤大小、病理类型、肿瘤浸润深度、宫旁侵犯、手术切缘无关(P0.05);Lgr5、RACK-1阳性高表达组患者的3年生存率、生存时间低于Lgr5、RACK-1阳性低表达组患者,差异有统计学意义(P0.05)。结论:RACK-1、Lgr5在CC组织中表达上调,并与部分临床病理特征及预后有关,检测RACK-1、Lgr5有助于CC患者的诊断及预后评估。     

Raf kinase inhibitor protein mediated signaling inhibits invasion and metastasis of hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is the most common type of liver cancer with high mortality and poor prognosis. Mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways have been implicated in promoting tumor cell proliferation and invasion of HCC cells.MethodsAs a potential inhibitor of tumor metastasis, the role of Raf kinase inhibitor protein (RKIP) in HCC development and the functional relevance with MAPK and NF-κB signaling pathways were investigated. The levels of RKIP expression were examined in human HCC tissues and correlated with tumor stages and metastatic status. Function of RKIP in cellular proliferation, migration, invasion and apoptosis was investigated in HCC cell lines by either overexpressing or knocking down RKIP expression. Mouse xenograft model was established to assess the effect of RKIP expression on tumor growth.ResultsOur results demonstrated decreased RKIP expression in HCC tissues and a strong correlation with tumor grade and distant metastasis. Manipulation of RKIP expression in HCCLM3 and HepG2 cells indicated that RKIP functioned to inhibit HCC cell motility and invasiveness, and contributed to tumor growth inhibition in vivo. Mechanistic studies showed that the function of RKIP was mediated through MAPK and NF-κB signaling pathways. However, cell type-dependent RKIP regulation on these two pathways was also suggested, indicating the complex nature of signaling network.ConclusionOur study provides a better understanding on the molecular mechanisms of HCC metastasis and sets the foundation for the development of targeted therapeutics for HCC.     

宫颈癌术后复发的危险因素及SCC-Ag、HR-HPV对复发的预测价值分析

目的:分析宫颈癌术后复发的危险因素,探讨鳞状细胞癌抗原(SCC-Ag)、高危型人乳头瘤病毒(HR-HPV)对宫颈癌术后复发的预测价值。方法:对2010年1月至2017年12月我院收治的宫颈癌患者300例进行回顾性分析,收集其临床资料,所有患者随访2年,定期检测SCC-Ag表达情况及HR-HPV感染情况,根据患者复发情况分为复发组与未复发组,应用单因素和多因素Logistic回归分析宫颈癌术后复发的危险因素,以病理诊断为金标准,分析SCC-Ag、HR-HPV对宫颈癌术后复发的预测价值。结果:随访期间出现12例失访,300例患者中完成随访288例,出现复发40例,未复发248例。单因素分析结果显示宫颈癌术后复发与肿瘤直径、分化程度、肿瘤间质浸润情况、临床分期、淋巴结转移、SCC-Ag阳性表达、HR-HPV持续感染有关(P0.05),而与发病年龄、体质量指数(BMI)、吸烟史、性行为开始年龄、宫颈癌家族史、病理类型、术后放化疗无关(P0.05)。多因素Logistic回归分析显示:中低分化、深肌层浸润、临床分期IIA1-IIA2期、有淋巴结转移、SCC-Ag阳性、HR-HPV持续感染是宫颈癌术后复发的危险因素(P0.05)。SCC-Ag联合HR-HPV预测宫颈癌术后复发的灵敏度、特异度、阳性预测值、阴性预测值分别为92.50%、87.50%、54.41%、98.64%。结论:中低分化、深肌层浸润、临床分期IIA1-IIA2期、有淋巴结转移、SCC-Ag阳性、HR-HPV持续感染是宫颈癌术后复发的危险因素,SCC-Ag联合HR-HPV预测宫颈癌术后复发具有一定价值,值得临床关注。