CXCL1在食管胃交界处腺癌中的表达及与患者预后的关系

目的 检测趋化因子1(CXCL1)在食管胃交界部腺癌中的表达,探讨其在癌症预后评价中的作用.方法 采用免疫组织化学的方法,检测2010年至2012年被河南省肿瘤医院确诊为食管胃交界部腺癌且有组织蜡块的121例癌症患者组织中CXCL1的表达,并经随访统计各位患者生存期情况.用χ2检验的方法比较CXCL1的表达差异,用Kaplan Meier法分析其生存情况,并用Log rank test比较,预后分析采用多因素Cox回归.结果 92例(76.03%)为CXCL1阳性表达,29例(23.97%)为阴性表达,且CXCL1的表达在高中分化、III或IV期及有淋巴结转移的患者中,均显著增高.CXCL1表达阳性的患者,无病生存期及总生存期较表达阴性的患者显著缩短,且经Cox多因素分析,CXCL1的表达、癌症分化程度、分期、淋巴结的转移都是影响无病存活期与总生存期的重要因素.结论 CXCL1可能与食管胃交界处腺癌的发生、发展及预后有关,或可作食管胃交界部腺癌判断预后及治疗的一个新的分子靶点.     

胃腺癌中p53、E-cadherin的表达及其预后因素分析

目的 研究胃腺癌组织中p53、E-cadherin的表达,分析它们和临床病理参数对预后的影响.方法 采用组织芯片和免疫组化检测150例胃腺癌中p53、E-cadherin的表达,分析它们和临床病理参数对预后的影响.单因素分析用Kaplan-Meier法计算累积生存率并比较患者术后平均生存时间,多因素分析用COX回归.结果 150例胃腺癌中p53阳性率为31.3%;E-cadherin阳性率为91.3%.随访到的74例胃腺癌患者1年生存率为83.8%,3年生存率为70.3%,5年生存率为63.5%.单因素分析年龄、分化程度、Laurén分类、浸润深度、淋巴结状况、pTNM分期是影响胃腺癌预后的因素;多因素分析p53、年龄、淋巴结状况为影响胃腺癌预后的独立因素(P<0.05).结论 p53、年龄、分化程度、Laurén分类、浸润深度、淋巴结状况和pTNM分期是影响胃腺癌预后的因素,而E-cadherin和组织学分类不是影响胃腺癌预后的因素.     

Wntless在胃腺癌组织中表达及其意义

目的观察Wnt蛋白分泌相关的基因Wntless在胃癌腺癌细胞和癌旁正常黏膜细胞的表达,分析Wntless表达与胃腺癌病理指标之间相关性和临床意义。方法用免疫组化法检测胃腺癌组织和胃癌旁正常黏膜中Wntless的蛋白表达。结果在104例胃癌标本中,Wntless在胃腺癌组织中表达为:7.7%(8/104)例为0或1+、36.5%(38/104)例为2+、55.8%(58/104)例为3+;在癌旁正常黏膜表达为:71.2%(74/104)例为0或1+,19.2%(20/104)例为2+,9.6%(10/104)例为3+。Wntless在胃腺癌组织中的表达显著高于胃癌旁正常黏膜表达(P0.001)。Wntless蛋白表达与肿瘤分化呈正相关(P0.05),与淋巴结转移呈正相关(P0.05)。结论 Wntless蛋白在胃腺癌中高表达,可能对肿瘤发生和进展等发挥了促进作用,并可能为新的靶向治疗提供分子靶标。     

SERPINE1对胃腺癌病人预后、免疫及细胞功能的影响

目的 探讨SERPINE1在胃腺癌中的表达及其对患者预后的影响。方法 应用GEPIA检索胃腺癌预后基因,并分析排名前10位的的预后基因在胃腺癌和胃正常组织中是否存在差异。HPA数据库分析SERPINE1在胃腺癌组织表达。STRING和GeneMANIA数据库分析SERPINE1的相关作用蛋白。TIMER数据库分析SERPINE1是否与胃腺癌免疫及预后是否相关。siRNA抑制SERPINE1表达,Quantitative Real-time PCR验证抑制情况。应用MTT和Transwell研究SERPINE1对胃腺癌细胞增殖和侵袭影响。结果 我们发现SERPINE1是胃腺癌预后差异基因;同时,SERPINE1高表达与胃腺癌病人总生存期和无病生存期相关。抑制SERPINE1表达后,胃癌细胞的增殖和侵袭能力降低。TIMER数据库分析证明SERPINE1与胃腺癌免疫细胞浸润相关。我们通过STRING和GeneMANIA数据库发现PLG,PLAT,PLAU,PLAUR和VTN在PPI中与SERPINE1密切相关。结论 SERPINE1在胃组织中不表达,在胃腺癌中表达;其高表达与胃腺癌患者不良的...     

胃腺癌组织中PD-L1与HER-2的表达及临床意义

目的观察胃腺癌中PD-L1的表达,分析PD-L1与HER-2表达的相关性及对预后的影响。方法收集西安交通大学第一附属医院存档的75例胃腺癌标本,采用免疫组化MaxVision法及FISH技术检测PD-L1、HER-2的表达。结果 75例胃腺癌中,PD-L1阳性43例,阳性率为57.3%,HER-2过表达13例,过表达率为17.3%。胃腺癌中PD-L1表达与分化程度呈负相关(r=-0.26,P0.05);相关性分析显示,PD-L1表达与HER-2表达呈正相关(r=0.25,P=0.029)。生存分析中HER-2及PD-L1不同表达组中HER-2过表达PD-L1阳性组的5年生存率最低,且HER-2表达是影响胃腺癌患者生存期的独立预后因素。结论 PD-L1相关治疗可成为胃腺癌治疗的新靶点。在胃腺癌中联合应用PD-L1与抗HER-2治疗可能成为胃腺癌治疗的新途径。     

胃腺癌预后评估中Tiam1蛋白过表达的意义

目的探讨T淋巴瘤转移诱导因子1(T-cell lymphoma invasion and metastasis-inducing factor 1,Tiam1)过表达在胃腺癌(gastric adenocarcinoma,GAC)临床预后评估中的意义。方法采用免疫组化En Vision法检测Tiam1蛋白在102例GAC组织、21例胃异型增生组织和33例癌旁正常组织中的表达,并分析其过表达与GAC患者预后之间的关系。结果 GAC组织中Tiam1阳性率为85.3%(87/102),强阳性率为61.8%(63/102),均明显高于胃异型增生组织和癌旁正常组织(P均0.01)。Tiam1蛋白表达水平与GAC分化程度、临床分期、淋巴结转移及浆膜浸润密切相关(P均0.05),与患者性别、年龄及肿块大小等均无关。结论 Tiam1蛋白表达水平与GAC的发生、发展及预后密切相关,Tiam1蛋白过表达可成为GAC患者不良预后的重要指标之一。     

胃腺癌中RAI14的表达及其临床意义

目的探讨维甲酸诱导蛋白14(retinoic acid induced protein 14, RAI14)在胃腺癌组织中的表达及其与临床病理特征的关系。方法收集58例胃浸润性腺癌,采用免疫组化EliVision两步法检测RAI14蛋白表达,并分析其表达与临床病理特征的关系,并与TCGA数据库样本分析结果进行比较。结果胃浸润性腺癌中RAI14高表达率为58.6%,与周围正常胃黏膜相比差异有显著性,所得结果与TCGA数据库样本分析结果一致;RAI14在肿瘤5 cm、低分化、有脉管侵犯、有淋巴结转移以及高分期病例中阳性率较高,分别为82.6%、81.2%、72.5%、72.2%、68.2%,差异有统计学意义(P0.05);与患者年龄、性别及神经侵犯并无相关性。结论 RAI14蛋白在胃腺癌中高表达,RAI14的高表达与肿瘤侵袭性相关临床病理特征有相关性,RAI14有望成为胃癌治疗的潜在靶点。     

丙酮酸羧化酶在胃腺癌中的表达及临床意义

目的 检测丙酮酸羧化酶(PC)在胃腺癌组织中的表达并分析其临床意义.方法 应用免疫组织化学方法及Western blot法检测PC蛋白在胃腺癌及其对应癌旁组织的表达情况,分析其在肿瘤中表达水平与患者年龄、性别、TNM分期及病理分级等临床病理资料之间的关系,并用Western blot法检测PC蛋白在不同分化胃癌细胞系及永生化胃黏膜上皮细胞系的表达情况.结果 免疫组化及Western blot法均显示PC在胃腺癌组织表达水平显著高于其对应癌旁组织(P＜0.01).PC高表达与患者TNM分期及病理分级显著相关(P＜0.05),而与患者性别、年龄无明显相关性(P＞0.05).Western blot法显示PC在不同分化胃癌细胞系表达水平显著高于永生化胃黏膜上皮细胞(P＜0.01).结论 PC高表达与肿瘤的恶性进展密切相关,提示PC有可能作为胃癌生物治疗的潜在靶点.     

胃腺癌组织中TGFβ1及其受体的表达及意义

转化生长因子β（transforming growth factorpl,TGFβ1）及其受体在胃癌、前列腺癌、肺癌及乳腺癌等多种恶性肿瘤的发生发展过程中起到了非常重要的作用,但对胃癌和癌前病变组织的系统研究较少。本文旨在通过免疫组织化学染色方法研究TGFβ1及其受体（TGFβRⅠ,Ⅱ）在胃腺癌、不典型增生、慢性萎缩性胃炎、肠上皮化生和正常胃黏膜组织中的表达,初步探讨这些蛋白对胃腺癌病变发展及预后的病理学意义。     

High RSF-1 expression correlates with poor prognosis in patients with gastric adenocarcinoma

Aim

To investigate the expression and prognostic significance of RSF-1 in gastric adenocarcinoma.

Methods

RSF-1 expression was analyzed using immunohistochemical staining on tissue samples from a consecutive series of 287 gastric adenocarcinoma patients who underwent tumor resections between 2003 and 2006.The relationship between RSF-1 expression, clinicopathological factors, and patient survival was investigated.

Results

Immunohistochemical staining indicated that RSF-1 is highly expressed in 52.6% of gastric adenocarcinomas. RSF-1 expression levels were closely associated with tumor size, histological differentiation, tumor stage, and lymph node involvement. Kaplan-Meier survival analysis showed that high RSF-1 expression exhibited a significant correlation with poor prognosis for gastric adenocarcinoma patients. Multivariate analysis revealed that RSF-1 expression is an independent prognostic parameter for the overall survival rate of gastric adenocarcinoma patients.

Conclusion

Our data suggest that RSF-1 plays an important role in gastric adenocarcinoma progression and that high RSF-1 expression predicts an unfavorable prognosis in gastric adenocarcinoma patients.     

Expression of SNCG,MAP2, SDF-1 and CXCR4 in gastric adenocarcinoma and their clinical significance

Objectives: The purpose of the study was to detect the expression of SNCG, MAP2, SDF-1 and CXCR4 in gastric adenocarcinoma, and to evaluate their roles in the carcinogenesis of gastric adenocarcinoma, development, invasion and metastasis as well as their clinical significance. Methods: The expression of SNCG, MAP2, SDF-1 and CXCR4 was detected by SP immunohistochemical method in 225 cases of gastric adenocarcinoma and 105 cases of nonneoplastic adjacent gastric tissue. The expression of SNCG, MAP2, SDF-1 and CXCR4 mRNA was also detected by RT-PCR method in 50 cases of gastric adenocarcinoma and 30 cases of nonneoplastic adjacent gastric tissue. Results: The expression of SNCG, MAP2, SDF-1 and CXCR4 in the gastric adenocarcinoma was remarkably higher than those in the nonneoplastic adjacent gastric tissue (P < 0.01); The positive expression of SNCG and MAP2 was correlated with the depth of tumor invasion and the metastasis of lymph nodes (P < 0.05), and that of SDF-1 and CXCR4 was correlated with the metastasis of lymph nodes (P < 0.05). Conclusions: SNCG, MAP2, SDF-1 and CXCR4 may play an important role in the carcinogenesis, progression, invasion and metastasis of gastric adenocarcinoma. However, it still needs more exploration whether they can serve as promising therapeutic targets of gastric adenocarcinoma.     

贲门腺癌中SFRP1、DKK3基因启动子区甲基化状态的联合分析

目的研究贲门腺癌(gastric cardia adenocarcinoma,GCA)中Wnt通路拮抗基因分泌型卷曲相关蛋白1(SFRP1)和DKK3(Dickkopf3)基因的甲基化状态,探讨其与贲门腺癌发生的关系。方法应用甲基化特异性PCR(MSP)法检测89例贲门腺癌及相应正常黏膜组织中SFRP1和DKK3基因的甲基化状态,并分析与临床病理参数间的关系。结果89例贲门腺癌组织中SFRP1和DKK3基因发生甲基化的分别有77例(86.5%)和16例(20.0%),而正常黏膜组织中仅有15例(13.9%)发生了SFRP1基因的甲基化,未发现有DKK3基因的甲基化现象,癌组织中两基因的甲基化率均明显高于正常黏膜组织(P0.05);SFRP1基因的高甲基化与肿瘤组织的淋巴结转移相关,而与肿瘤的浸润深度、临床分期及病理分级无关,DKK3基因的甲基化与各临床病理指标均无关(P0.05);联合分析SFRP1和DKK3基因,在贲门腺癌组织中两基因共同发生甲基化的有12例,其共同甲基化率与肿瘤的淋巴结转移及TNM分期相关(P0.05)。结论贲门腺癌中SFRP1和DKK3基因的高甲基化状态可能是引起贲门腺癌发生的分子机制之一;SFRP1、DKK3基因甲基化的联合检测对于贲门腺癌的预后评估有一定的参考价值。     

胃癌组织中AEG-1、Cyclin D1的表达及其意义

目的 观察胃癌组织中星形细胞上调基因-1(astrocyte elevated gene-1,AEG-1)、Cyclin D1的表达,分析二者表达与胃癌侵袭、转移的关系.方法 应用免疫组化EnVision法检测110例胃癌组织中AEG-1和Cyclin D1的表达,并复习相关文献.结果 AEG-1在胃癌组织中的阳性率为69.1％,AEG-1表达与癌组织Lauren分型、淋巴结转移、浸润深度和pTNM分期密切相关(P＜0.05),与患者性别、年龄、发生部位和肿瘤大小无关(P ＞0.05);Cyclin D1在胃癌组织中的阳性率为57.3％,Cyclin D1表达与癌组织浸润深度、淋巴结转移和pTNM分期有关(P＜0.05),与患者性别、年龄、发生部位、肿瘤大小和Lauren分型无关(P＞0.05).相关性分析显示,胃癌组织中AEG-1与Cyclin D1的表达呈正相关(P＜0.05).结论 AEG-1可能通过上调Cy-clin D1的表达而促进胃癌细胞的侵袭、转移.AEG-1可能作为胃癌治疗的一种潜在分子靶点.     

The utility of cytokeratin subsets in distinguishing Barrett's-related oesophageal adenocarcinoma from gastric adenocarcinoma

AIMS: Accurate tumour classification is critical for meaningful epidemiological studies in the assessment of cancer incidence rates and trends. Differentiating primary gastric carcinoma from oesophageal carcinoma can be difficult, especially when tumours are large and involve both the oesophagus and stomach. Furthermore, adenocarcinomas of both organs typically are of intestinal histological type and arise in a background of intestinal metaplasia. Consequently, histological markers that reliably distinguish Barrett's-related oesophageal adenocarcinoma from gastric adenocarcinoma would be useful. Cytokeratins (CK)7 and 20 are cytoplasmic structural proteins with restricted expression that help to determine the origin of many epithelial tumours including those of the gastrointestinal tract. The aim of this study was to determine the utility of co-ordinate CK7 and 20 expression in the distinction of Barrett's-related oesophageal adenocarcinoma from gastric adenocarcinoma arising in a background of intestinal metaplasia. METHODS AND RESULTS: CK7 and 20 immunostaining was performed on randomly selected surgical resection specimens from patients with Barrett's-related oesophageal adenocarcinoma (n = 30) and intestinal type gastric adenocarcinoma (n = 14) arising in a background of intestinal metaplasia. A CK7+ CK20- immunophenotype was demonstrated in 27 of 30 (90%) patients with Barrett's-related oesophageal adenocarcinoma and only three of 14 (21%) gastric adenocarcinomas. The sensitivity, specificity and positive predictive value of a CK7+/20- immunophenotype for a diagnosis of Barrett's-related oesophageal adenocarcinoma was 90%, 79%, and 90%, respectively. CONCLUSIONS: A CK7+/20- tumour immunophenotype is associated with Barrett's-related oesophageal adenocarcinoma and may be useful in accurate tumour classification, thus facilitating improving epidemiological evaluation of tumours at the oesophagogastric junction.     

胃癌组织中PD-L1的表达及其与预后的关系

为探讨共刺激分子PD-L1在胃癌组织中的表达及其临床意义。用免疫组织化学方法检测102例胃癌和10例胃腺瘤PD-L1的表达,并对其表达与患者年龄、性别、胃癌部位、肿瘤大小、组织类型、肿瘤浸润深度、分化程度、淋巴结转移等进行相关分析。结果:胃腺瘤组织和正常胃组织不表达PD-L1分子,胃癌组织中PD-L1呈阳性表达,表达阳性率为42.2%;PD-L1分子在胃癌组织中的表达与胃癌患者年龄、性别、肿瘤部位、组织学类型无关(P>0.05),与肿瘤大小、肿瘤的浸润深度、淋巴结转移及预后有关。当肿瘤大于5cm(P<0.05)、肿瘤浸润达深肌层、淋巴结转移阳性、生存期<2年时,PD-L1表达阳性率明显升高(P<0.01)。多变量分析还显示,PD-L1分子可作为评估胃癌预后的独立因素。胃癌组织PD-L1分子的检测有助于胃癌预后的判断和作为个体化治疗选择的生物学指标。