共表达甲状腺转录因子1与p40的非小细胞肺癌患者临床病理特征分析

目的探讨共表达甲状腺转录因子1(TTF-1)和p40的非小细胞肺癌(NSCLC)患者的临床病理特征。方法收集7例共表达TTF-1和p40的NSCLC患者的资料,回顾性分析其临床特征、病理形态、免疫表型及分子特征,并复习相关文献。结果患者中位年龄58岁,多为男性且吸烟者;影像显示为外周型肿块。肿瘤细胞呈实性巢状排列,瘤细胞呈圆形、卵圆形或多角形,胞质透明或嗜酸性,核分裂象>10个/10HPF;3例可见脉管内癌栓。同一群肿瘤细胞同时表达TTF-1和p40,CK7、p63、CK5/6和napsinA呈灶性或弥漫表达,增殖指数Ki-67阳性10%~90%。2例采用ARMS-PCR法分别检测到表皮生长因子受体(EGFR)18号外显子G719A/S/C突变和21号外显子L858R突变,1例采用二代测序法检测到TPM3-ROS1融合突变和ROS1(G2032R)突变。随访1~46个月,2例患者分别于22、46个月死亡,3例患者出现颈部淋巴结或脑转移。结论共表达TTF-1和p40的NSCLC具有独特的临床病理特征,临床进展快,预后差,可能是一种新的肿瘤实体。

Expression transformation of claudin-1 in the process of gastric adenocarcinoma invasion

AIM: To investigate the relation of expression transfor-mation of claudin-1 with invasiveness and metastasis of gastric carcinoma. METHODS: By using immunohistochemistry, expres-sion of claudin-1 in mucosa and invasive front of 136 gastric adenocarcinoma cases and proliferative index (Ki-67) were detected and analyzed. RESULTS: In mucosa, the claudin-1 over-expression rate of mucinous adenocarcinomas (including signet-ring cell carcinomas) was the highest. It was nega-tively related with the differentiation but positively related with the invasiveness and metastasis of gastric cancer. In invasive front, the claudin-1 over-expression rate was positively related with the differentiation, in-vasiveness and metastasis of gastric carcinoma. The expression transformation of claudin-1 was found in gastric carcinoma. The expression of claudin-1 in inva-sive front was transformed in 28/136 gastric carcinoma cases. The transformation rate in highly differentiated tubular adenocarcinomas was the highest (51.5%, 17/33). The deeper was the invasiveness, the higher was the transformation rate. The claudin-1 expression transformation rate in serosa and omenta was signifi -cantly higher (92.9%) than in tunica muscularis of in-vasive gastric cancer cases, as well as in patients withlymph node metastasis than in those without lymph node metastasis. CONCLUSION: Up-regulation of claudin-1 expres-sion and its transformation in invasive and metastatic gastric carcinoma suggest that claudin-1 participates in the transformation of biological behaviors in neo-plasms. Further study is needed to elucidate the pre-cise mechanism and the relation of claudin-1 expres-sion with the neoplasm progress.

TTF-1和P40共表达的非小细胞肺癌2例并文献复习

分析2例共表达甲状腺转录因子1(thyroid transcription factor-1,TTF-1)和蛋白40(protein 40,P40)的非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的临床病理学特征。2例患者均为老年男性,均有长期吸烟史,并伴有胸闷、胸痛、咳嗽等呼吸道症状;CT检查提示肺癌;镜下瘤细胞呈巢团状分布,具有类似鳞状上皮分化特征,可观察到细胞边界和细胞间连接,无腺腔结构和黏液。2例细胞角蛋白(cytokeratin,CK)7、TTF-1、CK5/6、P40、P63均呈弥漫强阳性,P53均呈突变型表达模式,无整合酶相互作用分子-1(integrase interactor-1,Ini-1)和染色质重塑复合物核心催化亚基-1(brahma-related gene 1,BRG-1)表达缺失,细胞增殖指数Ki-67增高。2例均发生肿瘤蛋白53(tumor protein 53,TP53)基因突变。同时具有腺上皮和鳞状上皮分化免疫表型的NSCLC极为罕见,迄今为止8篇文献(含本研究在内)共报道的12例共表达TTF-1和P40的NSCLC病例中,10例检测到TP53基因突变。因病例数极少,2021年世界卫生组织胸部肿瘤分类未提出确切的诊断分型和预后建议,仍需要更多的病例报道补充。

Expression,deleton and mnutation of ρ16 gene in human gastric cancer

AIM To investigate the relationship between the expression of p16 gene and the gastric carcinogenesis,depth of invasion and lymph node metastases, and to evaluate the deletion and mutation of exon 2 in p16 gene in gastric carcinoma.METHODS The expression of P16 protein was examined by streptavidin-peroxidase conjugated method (S-P); the deletion and mutation of p16 gene were respectively examined by polymerase chain reaction (PCR) and polymerase chain reaction single-strand conformation polymorphism analysis (PCR-SSCP) in gastric carcinoma.RESULTS Expression of P16 protein was detected in 96.25% (77/80) of the normal gastric mucosa, in 92.00% (45/50) of the dysplastic gastric mucosa and in 47.54% (58/122) of the gastric carcinoma. The positive rate of P16 protein expression in gastric carcinoma was significantly lower than that in normal gastric mucosa and dysplastic gastric mucosa (P＜0.05). The positive rate of P16 protein expression in mucoid carcinoma 10.00% (1/ 10) was significantly lower than that in poorly differentiated carcinoma 51.22% ( 21/ 41 ),undifferentiated carcinoma 57.69% (15/26) and signet ring cell carcinoma 62.50% (10/ 16) (P＜0.05). The positive rate of p16 protein in 30 cases paired primary and lymph node metastatic gastric carcinoma: There was 46.67% (14/30) in primary gastric carcinoma, 16.67% (5/30) in lymph node metastatic gastric carcinoma. The positive rate of lymph node metastatic carcinoma was significantly lower than that of primary carcinoma (P＜0.05). There was of p16 gene mutation in exon 2, but 5 cases displayed deletion of p16 gene in exon 2 in the 25 primary gastric carcinomas.CONCLUSIONS The expression loss of P16 protein related to the gastric carcinogenesis, gastric carcinoma histopathological subtypes and lymph metastasis. The mutation of p16 gene in exon 2 may not be involved in gastric carcinogenesis. But the deletion of p16 gene in exon 2 may be involved in gastric carcinogenesis.

Expression of some tumor associated factors in human carcinogenesis and development of gastric carcinoma

AIM: To study the effect of IGF-1/IGF-1R and gastrin/CCK-BR on carcinogenesis and development of human gastric carcinoma and to explore its mechanism and provide a credible theoretical foundation for early diagnosis and molecular therapy of gastric carcinoma.METHODS: mRNA expression levels of IGF-1/IGF-1R and gastrin/CCK-BR were assessed by RT-PCR method in gastric cancer tissues, adjacent mucosa, and tumor-free tissues from 56 patients with gastric carcinoma and normal gastric mucosae from 56 healthy controls. Tissue specimens were obtained by biopsy and confirmed by histological evaluation.RESULTS: The mRNA levels of IGF-1/IGF-1R were increased in gastric cancer tissues compared with normal tissues from healthy controls and successively increased in tumor-free tissues, adjacent mucosa, and gastric cancer tissues. The mRNA levels of gastrin/CCK-BR were increased in gastric cancer tissues compared with normal tissues from healthy controls. There was a significant difference between gastric cancer tissues and adjacent mucosa and tumor-free tissues, but the mRNA levels of gastrin were not significantly increased in adjacent mucosa and gastric cancer tissues compared with tumorfree tissues. The mRNA levels of CCK-BR were increased in gastric cancer tissues and adjacent mucosa compared with tumor-free tissues, but not significantly increased in adjacent mucosa and gastric cancer tissues compared with gastric cancer tissues.CONCLUSION: Overexpression of IGF-1/IGF-1R and gastrin/CCK-BR promotes the disorderly proliferation of gastric mucosa epithelia and it is of great significance in the carcinogenesis and development of gastric carcinoma.

Feedback regulation between phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1 and transforming growth factor β1 and prognostic value in gastric cancer

BACKGROUND Phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1(PREX1)was reported to be overexpressed in some cancers and involved in cancer development,but its expression and significance in gastric cancer remain unclear.AIM To evaluate the expression of PREX1 in gastric cancer and its significance in the development of gastric cancer,especially to evaluate the potential mechanism of PREX1 in gastric cancer.METHODS Bioinformatic analysis was performed in order to examine the expression of PREX1 in gastric cancer.The relationship between the survival rate of gastric cancer patients and PREX1 expression was assessed by Kaplan Meier portal.The Gene Set Enrichment Analysis and the correlation between PREX1 and transforming growth factor(TGF)β1 pathway-related mediators were evaluated by cBioPortal for Cancer Genomics.Western blotting and reverse transcriptase polymerase chain reaction assay were used to test the role of TGFβ1 on the expression of PREX1.Western blotting and dual-luciferase reporter system was used to evaluate the effect of PREX1 on the activation of TGFβ1 pathway.Wound healing and Transwell assay were used to assess the effect of PREX1 on the metastasis activity of gastric cancer cells.RESULTS PREX1 was overexpressed in the gastric tumors,and the expression levels were positively associated with the development of gastric cancer.Also,the high expression of PREX1 revealed poor prognosis,especially for those advanced and specific intestinal gastric cancer patients.PREX1 was closely involved in the positive regulation of cell adhesion and positively correlated with TGFβ1-related mediators.Furthermore,TGFβ1 could induce the expression of PREX1 at both the protein and mRNA level.Also,PREX1 could activate the TGFβ1 pathway.The induced PREX1 could increase the migration and invasion activity of gastric cancer cells.CONCLUSION PREX1 is overexpressed in gastric cancer,and the high level of PREX1 predicts poor prognosis.PREX1 is closely associated with TGFβsignaling and promotes the metastasis of gastric cancer cells.

Expression of pituitary homeobox 1 gene in human gastric carcinogenesis and its clinicopathological significance

AIM： To investigate the effect of pituitary homeobox 1 （PITX1） expression in cases of human gastric cancer on cancer differentiation and progression, and carcinogenesis. METHODS： Using polyclonal PITX1 antibodies, we studied the expression of PITX1 in normal gastric mucosa, atypical hyperplasia, intestinal metaplasia, and cancer tissue samples from 83 gastric cancer patients by immunohistochemistry. Moreover, semi-reverse transcription polymerase chain reaction （semi-RT-PCR） was performed to detect the mRNA level of PITX1 in three gastric cancer cell lines and a normal gastric epithelial cell line. Subsequently, somatic mutations of the PITX1 gene in 71 gastric cancer patients were analyzed by a combination of denaturing high performance liquid chromatography （DHPLC） and DNA sequencing. RESULTS： Immunohistochemistry showed that PITXl was strongly or moderately expressed in the parietal cells of normal gastric mucosa （100%）, while 55 （66.3%） out of 83 samples of gastric cancers showed decreased PITXl expression. Moreover, PITXl expression was reduced in 20 out of 28 cases （71.5%） of intestinal metaplasia, but in only 1 out of 9 cases （11%） of atypical hyperplasia. More importantly, PITXl expression was significantly associated with the differentiation, position and invasion depth of gastric cancers （r = -0.316, P 〈 0.01; r = 0.213, P 〈 0.05; r = -0.259, P 〈 0.05, respectively）. Similarly, levels of PITXl mRNA were significantly decreased in 2 gastric cancer cell lines, BGC-823 and SGC-7901, compared with the normal gastric epithelial cell line GES-1 （0.306 ± 0.060 vs 0.722 ± 0.102, P 〈 0.05; 0.356 ± 0.081 vs 0.722 ± 0.102, P 〈 0.05, respectively）. Nevertheless, no somatic mutation of PITX1 gene was found in 71 samples of gastric cancer by DHPLC analysis followed by sequencing. CONCLUSION： Down-regulation of PITX1 may be a frequent molecular event in gastric carcinogenesis. Aberrant levels of PITXl expression may be closely correlated with the progression and differentiation of gastric cancer,

血清LncRNA MALAT1表达水平对EB病毒感染相关胃癌的诊断和预后价值研究

目的 探讨长链非编码RNAs(long non-coding RNAs,LncRNAs)肺腺癌相关转录物1(metastasis-associated lung adenocarcinoma tran 1,MALAT1)在EB病毒相关胃癌(EBV-associated gastric carcinoma,EBVaGC)患者血清中的表达及与患者预后的关系。方法 选取2015年1月~2017年1月河北北方学院附属第一医院消化内科收治的233例胃癌患者为研究对象,根据EBV DNA结果将患者分为EBV DNA阳性组(n=123)和EBV DNA阴性组(n=110);同时选取在该院进行健康体检的志愿者100例为对照组。实时荧光定量PCR(qRT-PCR)法检测血清LncRNA MALAT1水平;受试者工作特征(ROC)曲线分析LncRNA MALAT1水平对EBVaGC患者诊断的敏感度及特异度;利用KaplanMeier法分析LncRNA MALAT1表达与患者生存时间的关系;采用多因素COX回归风险模型分析EBVaGC患者的预后影响因素。结果 EBV DNA阳性组EBVaGC患者血清中LncRNA MALAT1表达水平高于EBV DNA阴性组和健康对照组(1.27±0.03 vs 1.12±0.05,0.96±0.04),差异有统计学意义(F=1620.239,P=0.000);EBVaGC患者血清中LncRNA MALAT1表达与年龄、主癌位置、脉管癌栓、肿瘤直径、肿瘤组织学类型、神经侵犯、浸润深度无关(t=1.320~1.970,均P> 0.05),与性别、分化程度、淋巴结转移、TNM分期、Lauren分型有关(t=4.880~29.748,均P=0.000);ROC结果显示,LncRNA MALAT1预测EBVaGC患者的曲线下面积(AUC)为0.863(95%CI:0.811~0.906),敏感度和特异度分别为92.68%,81.00%;Kaplan-Meier分析结果显示,LncRNA MALAT1高表达组患者五年累积生存率34.62%(27/78)显著低于低表达组57.78%(26/45),差异有统计学意义(Log rankχ^(2)=6.944,P=0.008);COX结果显示,年龄、分化程度、淋巴结转移、TNM分期、LncRNA MALAT1高表达均是影响EBVaGC患者生存状况的危险因素。结论 EBVaGC患者血清中LncRNA MALAT1表达水平上调,与EBV感染相关胃癌的进展和预后密切相关,可作为诊断EBVaGC患者的潜在血清标志物。

胃癌患者癌组织和血清外泌体中LncRNA CCAT1、miR-140-3p表达及其临床意义

目的观察胃癌患者癌组织和血清外泌体中LncRNA结肠癌相关转录因子1(CCAT1)、微小核糖核酸-140-3p(miR-140-3p)表达情况并分析其临床意义。方法选取93例行胃癌根治术的胃癌患者为胃癌组,47例胃部良性病变患者为良性病变组,47例健康体检者为健康对照组。采集所有研究对象静脉血,提取血清外泌体,于胃癌患者行胃癌根治术过程中留取患者肿瘤组织样本及癌旁组织样本,采用RT-qPCR法检测血清外泌体及胃癌、癌旁组织中的LncRNA CCAT1、miR-140-3p。对胃癌患者随访5年,记录患者生存时间并计算5年生存率。采用Pearson相关分析法分析患者癌组织及血清外泌体中LncRNA CCAT1与miR-140-3p的相关性;比较不同病理特征胃癌患者癌组织及血清外泌体LncRNA CCAT1、miR-140-3p表达,以胃癌患者癌组织LncRNA CCAT1、miR-140-3p表达的平均值为界限,将患者分为高、低LncRNA CCAT1、miR-140-3p者,采用K-M生存曲线比较高、低LncRNA CCAT1、miR-140-3p患者5年总生存率;采用受试者工作特征(ROC)曲线分析血清外泌体LncRNA CCAT1、miR-140-3p对胃癌的诊断价值。结果患者胃癌组织LncRNA CCAT1表达高于癌旁组织,miR-140-3p表达低于癌旁组织(P均<0.05)。血清外泌体LncRNA CCAT1表达健康对照组<良性病变组<胃癌组,miR-140-3p表达健康对照组>良性病变组>胃癌组(P均<0.05)。Pearson相关分析显示,胃癌患者癌组织及血清外泌体中LncRNA CCAT1表达与miR-140-3p表达均呈负相关(r分别为-0.726、-0.639,P均<0.05)。不同肿瘤分化程度、浸润深度、临床分期及淋巴结转移情况的胃癌患者癌组织及血清外泌体中LncRNA CCAT1、miR-140-3p表达比较差异具有统计学意义(P均<0.05)。癌组织及血清外泌体LncRNA CCAT1高表达的胃癌患者5年总生存率低于LncRNA CCAT1低表达患者,miR-140-3p高表达的胃癌患者5年总生存率高于miR-140-3p低表达患者(P均<0.01)。ROC分析结果显示,血清外泌体LncRNA CCAT1、miR-140-3p预测胃癌的曲线下面积(AUC)分别为0.712、0.766,两者联合诊断胃癌的AUC为0.845。结论胃癌患者癌组织及血清外泌体中LncRNA CCAT1表达上调、miR-140-3p表达下调,其表达与患者肿瘤分化程度、浸润深度、临床分期及淋巴结转移情况及预后有关,血清外泌体LncRNA CCAT1、miR-140-3p联合对胃癌具有较高的诊断价值。

转录因子CREB3L1在甲状腺癌组织中的表达及生物学意义

目的探讨转录因子环腺苷酸响应元件结合蛋白3-样1(CREB3L1)在甲状腺癌(THCA)组织中的表达及其临床意义。方法从GEO、ArrayExpress、SRA、TCGA等数据库检索下载CREB3L1 mRNA在THCA组织中的表达谱,应用Wilcoxon非参数检验检测CREB3L1 mRNA在THCA组织和正常甲状腺组织中表达水平的差异;计算CREB3L1表达值的标准化均数差(SMD)及汇总受试者工作特征(SROC)曲线下面积等指标,综合评估CREB3L1 mRNA在THCA组织中的表达水平及其对THCA的区分能力。用上述数据集批量获取CREB3L1在THCA组织中的相关过表达基因,应用CistromeDB预测CREB3L1转录靶基因,用clusterProfiler对CREB3L1在THCA组织中的相关过表达基因、CREB3L1转录靶标交集基因进行基因本体和京都基因与基因组百科全书功能注释。在THPA数据库中查看CREB3L1蛋白在THCA组织中的表达水平。结果与正常甲状腺组织比较,THCA组织中CREB3L1蛋白表达水平呈上调趋势。基于基因芯片、高通量测序数据集共纳入1175例THCA组织和791例正常甲状腺组织样本。CREB3L1 mRNA在THCA组织中呈高表达[SMD=0.11,95%可信区间(95%CI):0.01~0.20],集成SROC曲线下面积为0.62(95%CI:0.57~0.66)。CREB3L1蛋白在THCA组织中高表达患者5年生存率比低表达者低。交叉基因主要富集在细胞周期信号通路上,主要生物学功能为细胞器裂解。细胞分裂周期6蛋白(CDC6)与CREB3L1呈正相关。结论CREB3L1在THCA组织中高表达不利于患者的预后,有可能通过靶向基因CDC6参与了THCA的发生、发展。

胃癌高表达转录本1对胃癌细胞株AGS增殖、周期的影响及其机制

目的观察胃癌高表达转录本1(GHET1)对胃癌细胞株AGS增殖、周期的影响,并探讨其机制。方法将干扰序列si-GHET1、阴性对照序列si-NC、空白对照序列转染进AGS细胞中(分别计为干扰组、阴性组、空白组),采用real-time PCR法检测各组细胞GHET1,CCK-8法检测细胞增殖能力,流式细胞术检测细胞周期,Western blotting法检测细胞周期相关蛋白。结果干扰组、阴性组、空白组GHET1相对表达量分别为0.42±0.06、1、1.15±0.19,干扰组与其余两组比较,P均<0.05;48 h细胞OD450值分别为0.57±0.04、0.93±0.05、1.03±0.06,72 h细胞OD450值分别为0.69±0.10、1.54±0.08、1.58±0.14,干扰组与其余两组比较,P均<0.05;G0/G1期细胞比例分别为62.01%±4.56%、47.03%±3.36%、44.65%±3.44%,S期细胞比例分别为20.34%±3.29%、32.25%±1.78%、32.96%±2.58%,干扰组与其余两组比较,P均<0.05;CDK2相对表达量分别为0.60±0.08、0.81±0.07、0.81±0.02,CDK4相对表达量分别为0.57±0.03、0.89±0.08、0.87±0.06,CDK6相对表达量分别为0.62±0.09、0.86±0.07、0.92±0.07,Cyclin D相对表达量分别为0.58±0.03、0.74±0.02、0.70±0.04,Cyclin E相对表达量分别为0.33±0.03、0.39±0.01、0.39±0.01,干扰组与其余两组比较,P均<0.05。结论 GHET1可促进AGS细胞增殖,缩短细胞周期,其机制可能通过上调细胞周期相关蛋白表达来实现。

HMGB1过表达和沉默影响子宫内膜癌HEC-1A细胞增殖和侵袭及其机制

目的:探讨HMGB1基因过表达和沉默对子宫内膜癌增殖与侵袭能力的影响及其机制。方法:构建含有HMGB1重组质粒和HMGB1 sh RNA的慢病毒载体并转染人子宫内膜癌HEC-1A,建立过表达和沉默HMGB1基因的HEC-1A细胞株。采用细胞增殖/毒性活性检测试剂盒(cell counting kit-8)、Transwell小室、细胞划痕实验分析HMGB1过表达和沉默对子宫内膜癌HEC-1A细胞生长、增殖、侵袭及转移的影响。采用Western印迹和反转录PCR(reverse transcriptionPCR,RT-PCR)检测过表达和沉默HMGB1后HEC-1A细胞中NF-κB,VEGF及基质金属蛋白酶2(matrix metalloproteinase2,MMP2)的表达情况。结果:过表达HMGB1能够促进子宫内膜癌HEC-1A细胞增殖、侵袭与转移,且HEC-1A细胞中NF-κB,VEGF及MMP2表达上调;干扰HMGB1表达抑制HEC-1A细胞增殖、侵袭与转移,HEC-1A细胞中NF-κB,VEGF及MMP2表达下调。结论:HMGB1与子宫内膜癌增殖、侵袭与转移密切相关,且可能通过NF-κB,VEGF及MMP2影响子宫内膜癌的侵袭与转移;HMGB1可能成为治疗子宫内膜癌的一个重要靶点。

Kiss-1和AEG-1在胃癌中的表达及其相关性

目的探讨Kiss-1和AEG-1在胃癌组织中的表达及其相关性。方法采用RT-PCR和免疫组织化学法检测77例胃癌组织和20例正常胃组织中Kiss-1和AEG-1的表达,进一步用Western blot方法检测Kiss-1和AEG-1在胃癌组织和正常胃组织中表达。结果 RT-PCR结果发现胃癌组织中Kiss-1 mRNA表达水平显著低于正常胃组织(P<0.05),AEG-1mRNA表达水平显著高于正常胃组织(P <0. 05);免疫组化和Western blot发现胃癌组织中Kiss-1蛋白表达水平显著低于正常胃组织(P <0.05),AEG-1蛋白表达水平显著高于正常胃组织(P <0.05);Kiss-1 mRNA及蛋白阳性表达与胃癌组织的浸润深度、淋巴结转移有关(P<0.05);AEG-1 mRNA及蛋白阳性表达与胃癌组织的分化程度有关(P <0.05);胃癌组织中Kiss-1和AEG-1的表达呈负相关。结论 Kiss-1在胃癌组织中表达降低,AEG-1在胃癌组织中表达升高,Kiss-1、AEG-1可能参与胃癌的发生、发展以及浸润并有望成为诊断胃癌的生物学标记。

10例胃小细胞型神经内分泌癌的临床病理分析

目的观察胃小细胞型神经内分泌癌(SCNEC-G)的临床病理特点,探讨其诊断及鉴别诊断要点,提高其病理诊断准确性,为其综合治疗提供依据。方法对2010年至2015年10例SCNEC-G根治手术标本的组织切片行光镜观察,经免疫组织化学标记,分析突触素(Syn)、嗜铬蛋白A(CgA)、神经细胞黏附分子(CD56)、甲状腺转录因子-1(TTF-1)蛋白和Ki-67的表达情况。结果 SCNEC-G呈浸润性生长,癌细胞呈弥漫、大小不等巢团状、条梭状排列,部分病例局灶可呈假腺样结构,肿瘤表面及肿瘤内部均可见核碎屑和凝固性坏死,癌细胞小,呈圆形、卵圆形、短梭形,核深染,核仁不明显,可见较多核分裂。10例癌组织浸润深度为胃壁深肌层至全层,部分病例浸润至胃壁周围脂肪组织,所有样本均有神经侵犯和脉管内癌栓。10例SCNEC-G患者中,Syn、CgA、CD56、TTF-1、Ki-67阳性至强阳性表达率分别为80.0%、70.0%、80.0%、40.0%和100.0%。结论 SCNEC-G对神经源性抗原敏感性较高,同时部分病例TTF-1阳性表达,在原发灶不明的TTF-1阳性转移性小细胞癌中,仍需考虑SCNEC-G的可能。

血清IFN-γ和STAT1的检测在胃癌中的临床意义

目的:检测胃癌患者血清IFN-γ和STAT1的表达,探讨其与胃癌临床及病理指标的关系.方法:应用ELISA方法检测42例胃癌患者血清标本中IFN-γ和STAT1的表达,与40例同期正常对照者的血清标本作对比分析.同时采用单因素方差分析和Spearman相关分析探寻IFN-γ和STAT1的表达浓度与胃癌病理类型、病理分期及TNM分期的关系.结果:胃癌患者血清IFN-γ与STAT1的表达显著低于正常对照者(t=-10.587,-8.711,均P=0.000).在胃癌患者中,除IFN-γ的表达在印戒细胞癌和腺癌Ⅱ-Ⅲ级之间有显著差异外(t=0.374,P=0.023),其余指标在不同病理类型、分期及TNM分期之间均无显著差异.Spearman相关分析显示IFN-γ与STAT1的表达与病理类型、分期及TNM分期无显著相关性.结论:血清IFN-γ与STAT1的表达与胃癌的发病密切相关,可作为协同判断胃癌发病的指标.

水通道蛋白4和高迁移率族蛋白1在晚期胃癌中的表达

【目的】研究晚期胃癌组织中水通道蛋白4(AQP4)和高迁移率族蛋白1(HMGB1)表达,探讨它们表达的临床意义。【方法】选择1999年11月至2005年6月在中山大学肿瘤医院接受FOLFOX或PLF方案化疗的Ⅳ期胃癌患者60例进行研究。胃癌组织病理蜡块切片,采用免疫组化方法检测其中AQP4和HMGB1蛋白表达情况并进行评分。Kaplan-Meier方法分析HMGB1表达与无进展生存时间(PFS)、总生存时间(OS)的关系。【结果】在60例已行FOLFOX或PLF方案治疗的胃癌患者标本中,3例腺癌标本中AQP4阳性(5%),肿瘤旁相对正常的胃腺体表达全部强阳性(100%)。HMGB1在18例标本中表达(30%)阳性,其中13例来自于FOLFOX治疗组(31%,13/42),5例来自于PLF组(31.3%,5/16),两组的阳性率无差异(P=0.806)。生存分析显示阳性与阴性表达的患者无进展生存期和总生存期差异无统计学意义。【结论】AQP4和HMGB1选择性在部分晚期胃癌组织中表达增加,它们在胃癌的发生、发展中的临床意义需进一步扩大样本研究。

原癌基因Fra-1在胃癌组织中的表达及临床意义

目的:探讨胃癌组织中Fra-1 mRNA的表达及临床意义。方法:收集50例胃癌标本及相关临床病理资料,以RT-PCR方法检测胃癌组织、癌旁正常组织中Fra-1 mRNA的表达情况。结果:Fra-1 mRNA在胃癌组织中的表达高于癌旁正常组织(P<0.01),而其表达在胃癌的淋巴结转移、浸润深度、TNM分期间差异均有统计学意义(P<0.05),而在患者的性别、年龄、肿瘤分化程度和大小间差异均无统计学意义(P>0.05)。结论:Fra-1的高表达可能与胃癌的发生及侵袭转移有关,可能成为胃癌早期诊断的分子指标及分子靶向治疗的新靶点。

TTF-1蛋白在非小细胞肺癌中的表达及临床意义

目的探讨甲状腺转录因子-1(TTF-1)蛋白在非小细胞肺癌(NSCLC)中的表达特点及其与患者临床病理特征的关系。方法选取167例本院胸外科术后病理证实为NSCLC患者的肺癌组织标本,采用免疫组织化学法检测本组病理标本中TTF-1蛋白的表达情况,并分析其表达情况与NSCLC患者的临床病理特征的关系。结果 167例组织标本中TTF-1蛋白阳性表达95例(56.89%)。TTF-1蛋白在TNM分期Ⅲ+Ⅳ期、发生淋巴结转移、腺癌患者中呈现高表达,其阳性表达率分别为70.73%、75.36%、83.00%,显著高于TNM分期Ⅰ+Ⅱ期(43.53%)、未发生淋巴结转移(43.88%)、鳞癌患者(17.91%),且差异均具有统计学意义(P<0.01);TTF-1蛋白表达与NSCLC患者的年龄、性别、分化程度的关系无统计学意义(P>0.05)。结论 TTF-1蛋白在非小细胞肺癌组织中阳性表达率较高,并且与TNM分期、病理类型、淋巴结转移具有一定的关系。

RT-PCR检测胃癌NY-ESO-1抗原的表达及其基因克隆

目的:研究NY-ESO-1基因在胃癌中的表达,以便了解为胃癌患者是否可以使用NY-ESO-1抗原为基础的疫苗治疗。方法:采用RT-PCR方法检测了NY-ESO-1基因在60例胃癌组织和相应的癌旁正常组织中的表达,采用分子克隆的方法从胃癌组织中克隆了NY-ESO-1cDNA。结果:NY-ESO-1基因在胃癌组织中的表达率为55%(33/60),在相应的癌旁正常组织中的未见表达,克隆的NY-ESO-1cDNA序列与GenBank报道一致。结论:NY-ESO-1基因在胃癌中的高表达率,NY-ESO-1抗原可以被具有HLA-1类分子限制性CTL识别。

血清STAT1和肿瘤标志物联合检测对胃癌的诊断价值

目的检测胃癌患者血清信号传导及转录激活因子1(STAT1)和传统肿瘤标志物的表达,探讨血清STAT1与肿瘤标志物的联合检测对胃癌的诊断价值。方法选择83例胃癌患者(胃癌组),其中男性51例,女性32例;年龄32~74岁,平均年龄60.02岁。同期40例胃良性溃疡患者(溃疡组),其中男性24例,女性16例;年龄35~68岁,平均年龄58.85岁。40例健康志愿者(正常对照组),其中男性21例,女性19例;年龄35~65岁,平均年龄58.75岁。取其血清标本,应用酶联免疫吸附分析(ELISA)方法检测STAT1的表达,并检测肿瘤标志物[癌胚抗原(CEA)、糖类抗原(CA)19-9、CA72-4、CA50、甲胎蛋白(AFP)]的表达,比较不同分期胃癌患者STAT1和肿瘤标志物的表达。结果胃癌组血清STAT1平均浓度(66.38±48.72)μg/L,显著低于溃疡组[(120.98±52.26)μg/L](P=0.000)和正常对照组[(93.15±36.92)μg/L](P=0.006)。STAT1+5项肿瘤标志物联合检测可提高灵敏度(42.17%vs 34.94%)(P=0.028),特异度差异无统计学意义(77.50%vs 83.75%)(P=0.257)。血清STAT1在胃癌各期患者中的灵敏度差异无统计学意义(P=0.923)。结论血清STAT1的表达与胃癌的发病密切相关,可作为传统肿瘤标志物的补充,对胃癌的早期诊断有积极意义。