血红素氧合酶-1在胃癌腹膜转移中的表达及意义

目的 探讨血红素氧合酶-1(hemeoxygenase-1,HO-1)在胃腺癌及腹膜转移灶、细胞系及耐药细胞系中的表达及意义.方法 用免疫组化法检测68例胄腺癌组织及其腹膜转移灶、转移灶旁无瘤腹膜组织中HO-1的表达,以及46例无腹膜转移的胃腺癌组织中HO-1的表达.Western印迹法检测胃腺癌腹膜转移组织及耐药细胞系HO-1的表达.结果 胃腺癌及其腹膜转移灶HO-1的阳性表达率分别为39.7%(27/68)和41.2%(28/68),显著高于癌旁无瘤腹膜组织[0%(0/68),P<0.01],亦显著高于无腹膜转移胃癌组织[21.7%(10/46),P<0.05].低分化转移灶HO-1表达水平显著高于中、高分化转移灶(P<0.05).Western印迹法检测胃癌腹膜转移患者的转移灶HO-1表达水平显著高于其癌旁无瘤腹膜组织(P<0.05).HO-1在耐药细胞系GC9811-P的表达水平较其亲本细胞系明显上调(P<0.05).结论 HO-1在胃腺癌腹膜转移过程中表达增高,HO-1可能参与胃癌腹膜转移发生.高表达HO-1与胃癌腹膜转移组织的恶性程度有关,其信号转导通路可能存在于组织的上皮细胞,并可能与多药耐药有关.     

MTA1基因表达与人胃癌的浸润和转移

目的:探讨MTA1基因在胃癌及癌周组织中的表达及其表达水平与胃癌浸润和转移潜能的相关性.方法:采用荧光定量PCR及Western印迹技术,分别在mRNA和蛋白水平检测42例手术切除的人胃癌组织及癌旁组织中MTA1的表达,结合胃癌的临床生物学特征分析MTA1表达与胃癌病理类型、淋巴结转移的关系.结果:胃癌组织中MTA1mRNA相对量的表达显著高于癌旁胃黏膜组织(0.6711vs0.3940,P<0.01),蛋白水平表达与mRNA一致.低分化胃腺癌组织中的MTA1mRNA的相对量表达显著高于中高分化胃腺癌组织(0.7475vs0.3460,P<0.01),而伴有淋巴结转移的胃癌组织中MTA1mRNA的相对量表达明显高于不伴有淋巴结转移的胃癌组织(0.8128vs0.4933,P<0.01).结论:MTA1的表达与促进胃癌的转移相关,检测MTA1表达可作为预测胃癌生物学行为、判断胃癌患者预后的一个参考指标.     

鸟苷酸环化酶C和尾型同源盒转录因子2在胃癌及癌前病变组织中的表达及意义

目的 研究鸟苷酸环化酶C(GC-C)和尾型同源盒转录因子2(CDX2)基因与蛋白在胃癌及癌前病变组织中的表达并探讨其临床意义.方法 收集30例手术切除的胃癌及相应癌旁5 cm胃黏膜组织,另32例非胃癌患者胃镜下取活检标本,其中23例肠上皮化生、9例异型增生.应用逆转录(RT)-PCR检测GC-C和CDX2 mRNA在胃癌及癌旁组织中的表达,Western印迹和间接免疫荧光组化技术检测GC-C和CDX2蛋白的表达,同时检测两者在肠上皮化生和异型增生中的表达.结果 RT-PCR显示GC-C和CDX2 mRNA在胃癌中的表达率分别为20/30和19/30,显著高于癌旁组织(0/30和0/30,P值均=0.000).Western印迹检测GC-C和CDX2蛋白在胃癌组织中表达率分别为19/30和17/30,显著高于癌旁组织(0/30和0/30,P值均=0.000).免疫荧光检测GC-C和CDX2在癌旁组织中不表达,在肠上皮化生组织中表达率为39.1 %和39.1%、异型增生组织为55.6%和55.6%、胃癌组织为56.7%和60.0%,与癌旁组织间差异有统计学意义(P值均=0.000).但在肠上皮化生、异型增生和胃癌间阳性率比较差异无统计学意义(P值均＞0.05).两者在肠型胃癌中的表达高于弥漫型(P值分别=0.009和0.024),但与年龄、性别、病灶大小、临床病理分期、分化程度和淋巴结转移等因素无关(P值均＞0.05).在肠上皮化生和胃癌中GC-C与CDX2的表达呈正相关(r分别=0.4524和0.3845,P分别=0.0371和0.0408).结论 GC-C和CDX2的异常表达与胃黏膜癌变的发生有关,可能参与人胃腺癌致癌过程的调节,检测GC-C与CDX2有助于早期胃癌和胃癌前病变诊断.     

巨噬细胞抑制因子-1 mRNA在胃癌及癌前病变黏膜组织中的表达及其临床意义

目的 研究巨噬细胞抑制因子-1(MIC-1)mRNA在胃癌及胃癌前病变黏膜组织的表达,及其与临床病理特征间的关系.方法 采用半定量RT-PCR法检测MIC-1 mRNA在58例胃癌组织、30例对应的癌旁组织、19例胃癌前病变黏膜组织和8例胃慢性炎性反应黏膜组织的表达;对比分析其与胃癌临床病理特征的关系.结果 ①MIC-1 mRNA在胃癌中的表达阳性率和相对表达量分别为91.4%和0.751±0.222,均显著高于癌旁5 cm内组织(60.0%和0.546±0.287)和癌旁10 cm外组织(43.3%和0.481±0.209),P值均＜0.01.而癌旁5 cm内及癌旁10 cm外组织表达阳性率和相对表达量间差异无统计学意义(P＞0.05).②胃癌组织中MIC-1 mRNA的表达与肿瘤临床分期、侵袭深度,淋巴结转移及有无远处转移有关(P值均＜0.05),与患者性别,年龄、肿瘤分化程度、肿瘤直径无关(P值均＞0.05).③MIC-1 mRNA在胃癌组织的表达阳性率和相对表达量为91.4%和0.751±0.222,显著高于胃癌前病变黏膜组织(52.6%和0.528±0.077,P＜0.01).胃慢性炎症黏膜组织无表达.结论 MIC-1可能在胃癌的发生发展、侵袭和转移过程中起重要的作用.     

Med19在人胃癌中的表达及其临床意义

目的 研究Med19基因在人胃癌组织中的表达情况及临床意义.方法 应用免疫组化和RT-PCR方法检测Med19 基因在胃癌组织、癌旁胃组织及正常胃组织中的表达.结果 胃癌组织中Med19表达阳性率为71.7%(43/60),显著高于癌旁胃组织和正常胃组织(P<0.01).癌旁胃组织和正常胃组织中Med19多为阴性表达,少数为弱阳性表达,二者间差异无显著性(P> 0.05).Med19的表达与胃癌的细胞分化程度、淋巴结转移情况、TNM分期相关(P<0.05),而在不同年龄、性别、肿瘤大小、浸润深度的胃癌样本中表达差异无显著性(P> 0.05). 结论 Med19参与了胃癌的发生、发展过程,有望成为一个新的肿瘤治疗靶向因子.     

胃腺癌组织中碱性成纤维细胞生长因子mRNA的表达

背景碱性成纤维细胞生长因子(bFGF)是一种强有力的血管生成因子,与肿瘤发生关系密切。目前有关bFGF与胃癌关系的研究不多。目的研究胃腺癌组织中bFGFmRNA的表达,探讨bFGF在胃腺癌发生、发展中的作用。方法采用逆转录聚合酶链反应(RT鄄PCR)检测20例胃腺癌组织和相应癌旁组织(距肿瘤边缘5cm以上)中bFGFmRNA的表达,以恒定表达的GAPDH作为内参照。计算bFGFmRNA与GAPDHmRNA表达积分光密度值的比值(b/G),以反映组织中bFGFmRNA的相对表达量。结果胃腺癌组织的b/G比值显著高于癌旁组织(1.3173±0.1578对0.9427±0.1402,P<0.01);其中低分化腺癌的b/G比值显著高于高中分化腺癌(1.4232±0.1225对1.2013±0.1340,P<0.05),有淋巴结转移者的b/G比值显著高于无淋巴结转移者(1.4075±0.1375对1.1962±0.1286,P<0.05)。结论bFGF与胃腺癌的恶性程度和转移密切相关,对其发生、发展具有重要影响。     

胃腺癌组织RBMS1、AKAP12表达变化及其临床意义

目的 探讨胃腺癌组织RNA结合基序单链相互作用蛋白1(RBMS1)、A激酶锚定蛋白12(AKAP12)表达变化及其临床意义。方法 选择胃腺癌患者102例,取手术切除的胃癌组织及其癌旁组织(距肿瘤组织边缘5 cm以上,经病理检查明确为正常胃组织),采用免疫组化法检测RBMS1、AKAP12表达。比较胃癌组织与癌旁正常组织RBMS1、AKAP12阳性表达率,采用Pearson线性相关分析法分析胃癌组织RBMS1阳性表达与AKAP12阳性表达的关系。分析胃癌组织RBMS1、AKAP12阳性表达与临床病理特征的关系以及二者表达与预后的关系。结果 胃癌组织RBMS1阳性表达率显著高于癌旁正常组织,AKAP12阳性表达率显著低于癌旁正常组织(χ2分别为75.583、53.204,P均<0.05)。胃癌组织RBMS1阳性表达与AKAP12阳性表达呈负相关关系(r=-0.625,P<0.05)。胃癌组织RBMS1、AKAP12阳性表达与TNM分期、淋巴结转移有关(P均<0.05),与性别、年龄、肿瘤最大径、肿瘤部位、组织分化程度无关(P均>0.05)。所有患者术后随访2～36个...     

胃癌组织芯片中Argonaute蛋白表达分析

目的 检测胃癌Argonautel、Argonaute2、Argonaute3和Argonaute4蛋白表达,探讨其临床意义.方法 利用组织芯片技术结合免疫组化法检测100例胃癌组织和癌旁组织中Argonaute1、Argonaute2、Argonaute3和Argonaute4蛋白的表达.结果 胃癌组织中Argonautel、Argonaute2,Argonaute3和Argonaute4蛋白表达均显著高于癌旁组织(P＜0.05);Ⅱ～Ⅱ期胃癌中4种蛋白表达均显著高于癌旁组织(P＜0.05);Argonaute4蛋白在Ⅲ期胃癌中的表达显著高于Ⅰ～Ⅱ期胃癌(P＜0.05),Argonaute1、Argonaute2、Argonaute3蛋白在在Ⅰ～Ⅱ期胃癌与Ⅲ期胃癌间差异无统计学意义(P＞0.05).四种Argonaute蛋白的表达与胃癌患者的性别、年龄、淋巴结转移无相关性(P＞0.05).在胃癌组织中Argonautel、Argonaute2、Argonaute3和Argonaute4蛋白两两间表达存在相关性(P＜0.01).结论 胃癌的发生发展可能与Argonaute1、Argonaute2、Argonaute3和Argonaute4蛋白过表达有关.     

胃腺癌组织中HER-2蛋白表达及其与微血管密度的关系

目的观察胃腺癌组织中HER-2蛋白表达变化,并分析其与微血管密度(MVD)的关系。方法采用免疫组织化学SP法检测胃腺癌(64例)及其癌旁组织(30例)中的HER-2蛋白,采用抗CD34单克隆抗体标记血管内皮细胞以检测MVD,分析二者的关系。结果胃腺癌组织中,HER-2蛋白过表达率为23.4%(15/64),高于癌旁组织(P<0.01),且与组织学分型、浸润深度及pTNM分期均相关(P<0.05或<0.01);胃腺癌组织中,MVD高于癌旁组织(P<0.01),且与浸润深度、淋巴结转移及pTNM分期相关(P均<0.05);胃腺癌组织中,HER-2蛋白过表达与MVD呈正相关(r=0.531,P<0.05)。结论胃腺癌组织中HER-2蛋白过表达可能促进肿瘤进展,该机制可能与其促进肿瘤内血管生成有关。     

胃癌组织中5-脂氧合酶的表达及其与磷酸化Akt相的关性

目的:检测5-脂氧合酶(5-lipoxygenase,5-LOX)在胃癌组织中的表达,并探讨5-LOX对磷酸化Akt(phosphorylatedAkt,p-Akt)表达的影响.方法:采用逆转录-聚合酶链反应(RT-PCR)检测30例新鲜胃癌及癌旁正常组织标本中5-LOXmRNA表达水平;免疫印迹法(Westernblot)检测5-LOX和p-Akt蛋白的表达水平.结果:5-LOX在胃癌组织中的表达显著高于癌旁正常组织(76.7%vs40%,P<0.05,mRNA水平;56.7%vs30%,P<0.05,蛋白水平).p-Akt蛋白在胃癌组织中的表达也显著高于癌旁正常组织(56.7%vs26.7%,P<0.05).相关性分析表明,胃癌组织中5-LOX蛋白表达和p-Akt水平间无明显相关性(r=0.186,P>0.05).结论:5-LOX蛋白对胃癌的发生、发展有一定促进作用,但与PI3-K/Akt信号通路无关.     

Establishment and Characterization of a High Metastatic Potential in the Peritoneum for Human Gastric Cancer by Orthotopic Tumor Cell Implantation

The aim of this study was to establish an orthotopic implantation model with high metastasis of gastric cancer to the peritoneum which is more faithful to clinical metastasis. A human gastric carcinoma cell line, GC9811, was injected as a single-cell suspension into the stomach of nude mice. The cells from some peritoneum metastatic foci were expanded in vitro and subsequently implanted to the stomach wall of nude mice. By repeating the in vivo stepwise selection method for four rounds and cloning culture, we obtained a cell line designated GC9811-P, which developed peritoneal metastasis in 13 of 13 (100%) of mice, compared with only 20% of those implanted with parental GC9811. The metastatic foci in the peritoneum showed essentially the same histological appearance as those induced by parental cells. Tumor cell growth of GC9811-P in vitro was faster than that of GC9811. Motility assays demonstrated higher motility of GC9811-P than of GC9811. The adhesive ability of GC9811-P cells to laminin was lower than that of GC9811 cells, whereas the ability of GC9811-P cells to adhere to fibronectin was significantly higher than that of parental cells. Differences between GC9811-P and their parental GC9811 cells were found in expression levels of various molecules by flow cytometric and western blot. The findings indicated that up-regulation in the expressions of CD155, VEGF, syndecan-1, and syndecan-2 or down-regulation in the expressions of IL-6 and E-cadherin play an important role in the peritoneal metastasis of human gastric carcinoma cells. The high-metastatic cell line appears to be useful for investigating the mechanisms of peritoneal metastasis and preventing peritoneal metastasis of human gastric cancer.     

Expression and significance of CD44s, CD44v6, and nm23 mRNA in human cancer

AIM: To investigate the relationship between the expression levels of nm23 mRNA, CD44s, and CD44v6,and oncogenesis, development and metastasis of human gastric adenocarcinoma, colorectal adenocarcinoma,intraductal carcinoma of breast, and lung cancer.METHODS: Using tissue microarray by immuhistochemical (IHC) staining and in situ hybri-dization (ISH), we examined the expression levels of nm23mRNA, CD44s, and CD44v6 in 62 specimens of human gastric adenocarcinoma and 62 specimens of colorectal adenocarcinoma; the expression of CD44s and CD44v6in 120 specimens of intraductal carcinoma of breast and 20 specimens of normal breast tissue; the expression of nm23 mRNA in 72 specimens of human lung cancer and 23 specimens of normal tissue adjacent to cancer.RESULTS: The expression of nm23 mRNA in the tissues of gastric and colorectal adenocarcinoma was not significantly different from that in the normal tissues adjacent to cancer (P＞0.05), and was not associated with the invasion of tumor and the pathology grade of adenocarcinoma (P＞0.05). However, the expression of nm23 mRNA was correlated negatively to the lymph node metastasis of gastric and colorectal adenocarcinoma (r = -0.49, P＜0.01; r = -4.93, P＜0.01). The expression of CD44s in the tissues of gastric and colorectal adenocarcinoma was significantly different from that in the normal tissues adjacent to cancer (P＜0.05;P＜0.01). CD44v6 was expressed in the tissues of gastric and colorectal adenocarcinoma only, the expression of CD44v6 was significantly associated with the lymph node metastasis, invasion and pathological grade of the tumor (r = 0.47, P＜0.01; r = 5.04, P＜0.01). CD44sand CD44v6 were expressed in intraductal carcinoma of breast, the expression of CD44s and CD44v6 was significantly associated with lymph node metastases and invasion (P＜0.01). However, neither of them was expressed in the normal breast tissue. In addition, the expression of CD44v6 was closely related to the degree of cell differentiation of intraductal carcinoma of breast (x2= 5.68, P＜0.05). The expressional level of nm23mRNA was closely related to the degree of cell differentiation (P＜0.05) and lymph node metastasis (P＜0.01), but the expression of nm23 gene was not related to sex, age, and type of histological classification (P＞0.05).CONCLUSION: Patients with overexpression of CD44s and CD44v6 and low expression of nm23 mRNA have a higher lymph node metastatic rate and invasion. In addition, overexpression of CD44v6 is closely related to the degree of cell differentiation. Detection of the three genes is able to provide a reliable index to evaluate the invasion and metastasis of tumor cells.     

热休克蛋白70在人胃腺癌发展过程中表达的意义

目的 探讨人胃腺癌发展过程中热休克蛋白70（HSP70）的表达与病理分型、浸润深度和淋巴结转移的关系。方法 应用免疫组织化学S-P法检测52例人胃腺癌组织中HSP70的表达。结果 胃腺癌和黏液腺癌的HSP70阳性率分别为64.29%和60.00%；高分化和低分化腺癌的HSP70阳性率分别为67.86%和50.00%；胃腺癌HSP70的阳性率在不同病理分型、不同分化程度的肿瘤之间差别均无显著意义。侵犯深度达浆膜和肌层的胃腺癌HSP70阳性率分别为75.68%和33.33%（P〈0.05）。有淋巴结转移和无淋巴结转移组中HSP70阳性率分别为73.33%和45.45%（P〈0.05）。结论 人胃腺癌HSP70中阳性率与淋巴结转移、侵犯深度有关，与病理分型无关。提示胃腺癌晚期HSP70的表达高于早期胃腺癌，检测核指标可为早期诊断胃腺癌提供理论依据。     

Over-Expression of EphA2 and EphrinA-1 in Human Gastric Adenocarcinoma and Its Prognostic Value for Postoperative Patients

This study aims to investigate the expression and significance of EphA2 and EphrinA-1 in human gastric adenocarcinoma progression and prognosis. The expression of EphA2 and EphrinA-1 was detected in the cell lines and tissues of gastric adenocarcinoma. Different expression levels of EphA2 and EphrinA-1 were found in two cell lines. The expression of EphA2 and EphrinA-1 was significantly higher in gastric adenocarcinoma tissues than in normal tissues. Statistical analysis showed a significant correlation of EphA2 expression with the depth of tumor invasion, tumor-node-metastasis (TNM) stages, and lymph node metastasis. EphrinA-1 over-expression was significantly correlated with TNM stages and lymph node metastasis, while EphA2 expression was found to be an independent prognostic factor of postoperative gastric adenocarcinoma. In conclusion, the increased expression of EphA2 and EphrinA-1 plays an important role in the progression of human gastric adenocarcinoma, in which elevated EphA2 expression is an independent factor that indicates poor prognosis in postoperative gastric adenocarcinoma.     

miR-1180在胃癌中的表达及其对胃癌增殖、凋亡的影响

目的研究miR-1180在胃腺癌组织及胃癌细胞系中的表达及其对胃癌细胞增殖、凋亡的影响,探讨miR-1180在胃癌中可能的作用机制。方法应用qRT-PCR检测58例胃腺癌及20例癌旁正常组织中miR-1180的表达,分析其表达与胃腺癌临床病理特征的关系。检测miR-1180在胃癌细胞系中的表达,慢病毒干扰技术下调SGC-7901中miR-1180的表达,检测下调后对SGC-7901增殖、凋亡及细胞周期的影响。结果与癌旁正常组织比较,58例胃腺癌组织中miR-1180的表达明显增加(t=16.463,P=0.000),miR-1180的表达与患者的肿瘤大小、TNM分期及淋巴结转移有关(P均<0.05)。miR-1180在胃癌细胞系中表达升高(P=0.000),下调SGC-7901中miR-1180的表达,可见细胞增殖减少(3113±74 vs 1673±51,P=0.000),凋亡增加(4.313±0.220 vs 7.717±0.125,P=0.000);细胞周期G 1期细胞明显增加(45.89±0.33 vs 60.44±0.390,P=0.000),S期细胞明显减少(35.523±0.354 vs 21.953±0.444,P=0.000),G 2期细胞变化不大(18.587±0.672 vs 17.603±0.731,P=0.162)。结论miR-1180的表达促进胃癌的进展,胃癌中miR-1180的高表达与预后不良有关。     

Altered Expression of a Li-Cadherin in Gastric Cancer and Intestinal Metaplasia

The aims of this study were to examine Li-cadherin expression in 74 gastric carcinoma tissues, 10 cases with normal gastric tissues, and 21 cases with intestinal metaplasia and to investigate the role of Li-cadherin in cell differentiation, cancer invasion, and metastasis. Expression of Li-cadherin was analyzed by immunohistochemistry and semiquantitative polymerase chain reactio and correlated with clinicopathological parameters. Immunohistochemistry showed that Li-cadherin was mainly present on the cell membrane and there was no staining for liver–intestine cadherin in normal tissues. The reduction of Li-cadherin mRNA expression was inversely correlated with the grade of differentiation (P < 0.05). Significant differences in the expression of liver–intestine cadherin were found in lymphatic metastasis of the tumors (P < 0.05), but the expression of liver–intestine cadherin was not associated with gender (P=0.748), serosal invasion (P=0.136), TNM stage (P=0.172), Helicobacter pylori infection (P=0.572), liver metastasis (P=0.374), or peritoneal metastasis (P=0.621). Multivariate analysis revealed that the expression of Li-cadherin is an important predictor of lymph node metastasis. We conclude that there is a significant correlation between Li-cadherin expression and the differentiation of gastric carcinoma, and Li-cadherin can be a good marker to detect gastric cancer at early stages. Increased Li-cadherin expression may contribute to gastric cancer invasion to lymph nodes.     

基于Oncomine及TCGA数据集分析结肠肿瘤中HMGB1基因的表达及预后价值

目的研究结肠肿瘤中高迁移率族蛋白B1基因（HMGB1）的差异表达及预后价值。 方法从Oncomine及TCGA数据集中筛选出2 191例结肠肿瘤患者HMGB1基因表达数据及临床病理数据,采用Mann-Whitney U检验比较结肠癌与腺瘤、左半结肠癌与右半结肠癌、原位癌与浸润癌、黏液性腺癌与其他病理类型结肠癌、以及发生淋巴结转移与无淋巴结转移、发生远处转移与无远处转移结肠癌组织中HMGB1基因差异表达情况,并绘制Kaplan-Meier生存曲线。 结果HMGB1基因在结肠癌组织和腺瘤组织中均较正常结肠组织高表达（P<0.001）,在结肠癌组织中较结肠腺瘤组织中高表达,在左半结肠癌组织中较右半结肠癌高表达（P<0.05）,在黏液性腺癌组织中较其他病理类型低表达（P<0.05）,在浸润癌组织中较原位癌高表达（P<0.001）。有淋巴结转移及远处转移者较未转移者高表达（P<0.05）。HMGB1基因高表达提示更高的5年生存率（P=0.011）,尤其对于女性结肠癌患者（P=0.006）。 结论HMGB1基因可作为判断结肠癌浸润深度、淋巴转移、远处转移及预后的标志物。