SEMA3F蛋白在肝细胞癌中的表达及其预后价值

目的 研究SEMA3F蛋白在肝细胞癌(hepatocelluar carcinoma,HCC)中的表达及其预后价值.方法 采用Western Blotting法检测32例HCC及相应癌旁肝组织标本中SEMA3F蛋白的表达.运用免疫组织化学法检测38例HCC以及其相应癌旁组织中的SEMA3F蛋白的表达和微血管密度(microvassel dainty,MVD)值,分析SEMA3F蛋白表达水平与MVD的相关性.结果 SEMA3F蛋白在32例HCC组织中的表达明显低于相应的PCLT(447.78±48.26比618.93±61.23,P＜0.05).SEMA3F在HCC组织中的表达水平与肿瘤的结节数目及是否具有包膜结构密切相关(P＜0.05).SEMA3F低表达组的复发转移率显著高于高表达组(P＜0.01)而其术后生存率则显著低于高表达组(P＜0.01).SEMA3F高表达组的MVD值明显低于低表达组(86.56±17.94比115.6±30.38,P＜0.01).结论 SEMA3F在HCC组织中表达下调与肝癌复发转移率高和预后差密切相关,提示其可能是一个潜在的HCC预后分子标志物.

Abstract：

Objective To investigate the expression of Semaphorin 3F (SEMA3F) protein in hepatocellular carcinoma (HCC) and to demonstrate its relationship with clinicopathological features and prognosis of HCC. Methods Western Blotting was carried out in 32 hepatocellular carcinoma samples and matched perineoplastic tissues to detect the expression of SEMA3F protein. The relationship between SEMA3F protein expression and clinicopathological features as well as prognosis of HCC patients was analyzed. Immunohistochemistry was used to show the location of SEMA3F in HCC cells and its relationship with microvessel density (MVD). Results The expression of SEMA3F protein in HCC tissues was significantly higher than in the perineoplastic tissues (447.78± 48.26 vs 618.93 ±61.23, P＜0. 05) and it was correlated closely with tumor capsulation and tumor nodular number (P＜0.05). Based on the Western Blotting and clinical follow-up data, we found that the survival time of HCC patients with a higher SEMA3F expression level was longer than those with a lower level, and the recurrent/metastatic time of HCC patients was significantly different between these two groups (P＜0.01). Immunohistochemistry demonstrated that SEMA3F protein localized in the cytoplasm of HCC cells and its expression correlated with HCC MVD. MVD in the low-level group was higher than the high-level group (115.6±30.38 vs 86. 56±17.94, P＜0.01). Conclusions SEMA3F expression in HCC was significantly down-regulated and correlated closely with tumor-capsulation, nodular number, and MVD, implicating SEMA3F may play an important role in recurrence and metastasis of HCC. It can be regarded as a prognostic marker in HCC patients.     

肌动蛋白交联蛋白与血管内皮生长因子在肾细胞癌中的表达及其相关性

Objective To investigate the expression of Fascin and vascular endothelial growth factor (VEGF) in renal cell carcinoma (RCC) and the correlation with the biological behaviors. Methods The immunohistochemistry staining method was used to detect the expression of Fascin and VEGF in 92 cases of RCC and 20 cases of normal renal tissues as controls. Results The expression of Fascin in carcinoma tissue was significantly higher than that in normal tissues ( P ＜ 0. 05 ). Positive expression of Fascin and VEGF in renal cell carcinoma tissue was correlated with tumor grade ( P ＜ 0. 05 ) and clinical stage (P ＜0. 05 ) , but not with age, gender and different histological categories (P ＞ 0. 05 ). There was also a positive correlation between Fascin and VEGF (P ＜ 0. 05 ). Conclusion Fascin and VEGF are objective markers to estimate the behaviors of renal cell carcinoma.     

肌动蛋白交联蛋白与血管内皮生长因子在肾细胞癌中的表达及其相关性

Objective To investigate the expression of Fascin and vascular endothelial growth factor (VEGF) in renal cell carcinoma (RCC) and the correlation with the biological behaviors. Methods The immunohistochemistry staining method was used to detect the expression of Fascin and VEGF in 92 cases of RCC and 20 cases of normal renal tissues as controls. Results The expression of Fascin in carcinoma tissue was significantly higher than that in normal tissues ( P ＜ 0. 05 ). Positive expression of Fascin and VEGF in renal cell carcinoma tissue was correlated with tumor grade ( P ＜ 0. 05 ) and clinical stage (P ＜0. 05 ) , but not with age, gender and different histological categories (P ＞ 0. 05 ). There was also a positive correlation between Fascin and VEGF (P ＜ 0. 05 ). Conclusion Fascin and VEGF are objective markers to estimate the behaviors of renal cell carcinoma.     

肌动蛋白交联蛋白与血管内皮生长因子在肾细胞癌中的表达及其相关性

目的 探讨肌动蛋白交联蛋白(Fascin)与血管内皮生长因子(VEGF)在肾细胞癌组织的表达及与其生物学行为的关系.方法 采用免疫组织化学SP法检测Fascin与VEGF在92例肾细胞癌组织及20例正常肾脏组织中的表达.结果 Fascin及VEGF在肾细胞癌组织中的表达阳性率明显高于正常肾组织(P＜0.05);肾细胞癌组织中两种蛋白的表达与肿瘤组织学分级和临床分期均呈正相关(P＜0.05);与年龄、性别及肿瘤病理类型无明显相关(P＞0.05).且Fascin和VEGF的表达之间呈正相关(P＜0.05).结论 Fascin与VEGF可作为反映肾细胞癌生物学行为的参考指标.

Abstract：

Objective To investigate the expression of Fascin and vascular endothelial growth factor (VEGF) in renal cell carcinoma (RCC) and the correlation with the biological behaviors. Methods The immunohistochemistry staining method was used to detect the expression of Fascin and VEGF in 92 cases of RCC and 20 cases of normal renal tissues as controls. Results The expression of Fascin in carcinoma tissue was significantly higher than that in normal tissues ( P ＜ 0. 05 ). Positive expression of Fascin and VEGF in renal cell carcinoma tissue was correlated with tumor grade ( P ＜ 0. 05 ) and clinical stage (P ＜0. 05 ) , but not with age, gender and different histological categories (P ＞ 0. 05 ). There was also a positive correlation between Fascin and VEGF (P ＜ 0. 05 ). Conclusion Fascin and VEGF are objective markers to estimate the behaviors of renal cell carcinoma.     

KiSS-1、KiSS-1R及MMP-9表达与肝细胞癌侵袭转移的关系及意义

目的 检测肿瘤转移抑制基因KiSS-1及其配体KiSS-1R和基质金属蛋白酶-9(MMP-9)在肝细胞癌(HCC)中的表达,探讨KiSS-1表达与肝细胞癌侵袭转移的关系及其机制.方法 利用逆转录聚合酶链反应(RT-PCR)技术,检测HCC、癌旁肝组织及远癌肝组织中KiSS-1、KiSS-1R mRNA的表达情况;应用HCC组织芯片,结合免疫组化及彩色图像分析技术检测了KiSS-1、MMP-9蛋白在HCC芯片中各组织的相对表达量.结果 KiSS-1 mRNA在HCC中表达明显低于癌旁、远癌肝组织(P＜0.01).在转移组和临床Ⅲ期HCC中,KiSS-1蛋白的表达明显低于无转移及临床分期Ⅰ和Ⅱ期HCC(P＜0.01);KiSS-1在肝内转移灶中的表达量显著低于原发灶(P＜0.01).在转移组的HCC中,MMP-9表达量显著高于无转移的HCC(P＜0.01).在HCC组织中,KiSS-1和MMP-9的表达呈负相关性(r=-0.340,P＜0.01).结论 KiSS-1和MMP-9的表达失衡与HCC侵袭转移有关,KiSS-1的缺失表达可作为预测HCC转移潜能的有价值的参考指标.

Abstract：

Objective To detect the expression of KiSS-1, KiSS-1R and MMP-9 in hepatocellular carcinoma (HCC). To study the correlation of KiSS-1, KiSS-1R and MMP-9 expression with invasion and metastasis of HCC, and to explore the underlying mechanisms. Methods The expression of KiSS-1 , KiSS-1R mRNA in 33 HCC samples, 26 non-neoplastic adjacent liver tissue samples and 13 non-neoplastic distant liver tissue samples were detected by RT-PCR. Tissue chips were constructed by modified manual tools, which contained HCC, non-neoplastic adjacent liver tissues, non-neoplastic distant liver tissues, normal liver tissues and intrahepatic metastasis lesions. The expression of KiSS-1 and MMP-9 protein was determined by tissue chips, immunohistochemistry and semi-quantitative image analysis in 150 HCC, 137 non-neoplastic adjacent liver tissue, 98 non-neoplastic distant liver tissues, 16 normal liver tissues and 37 intrahepatic metastasis lesion samples. Results The results of RT-PCR showed that compared with the non-neoplastic adjacent liver tissues and the non-neoplastic distant liver tissues, the expression of KiSS-1 mRNA in HCC was significantly lower (P＜0.01). The expression of KiSS-1R mRNA did not changed in HCC and non-neoplastic liver tissues (P＞0.05). The expression of KiSS-1 protein was lower in HCC with metastasis and in clinical stage Ⅲ than that in those with non-metastasis, and in clinical stages Ⅰ and Ⅱ . It was also higher in the primary than in the metastasis lesions (P＜0.01, respectively). The expression of MMP-9 was higher in tumors having peplos invasion and metastasis than in those with negative peplos invasion and non-metastasis. It was lower in the primary than the metastasis lesions (P＜0. 01, respectively).Negative correlation between KiSS-1 and MMP-9 expression was found in HCC(r=- 0.340,P＜0.01). Conclusions The imbalance between KiSS-1 and MMP-9 expression might play an important role in enhancing the invasive and metastatic capacity of HCC. Loss of KiSS-1 expression might predict an aggressive clinical behavior and was associated with metastatic potential in HCC.     

食管鳞癌与细胞因子信号转导负调控因子3及其DNA甲基化的关系

目的 检测食管鳞癌(ESCC)组织中细胞因子信号转导负调控因子3(SOCS3)的DNA甲基化、mRNA及蛋白表达水平,探讨其在食管鳞癌发生、发展、浸润和转移中的作用.方法 采用甲基化特异性聚合酶链反应(MSP)、Real-Time聚合酶链反应(PCR)和Western blot法分别检测43例食管鳞癌组织中SOCS3的DNA甲基化、mRNA和蛋白表达水平,并与相应的癌旁正常食管组织进行对照研究,分析其与临床病理参数的关系.结果 (1)食管鳞癌组织SOCS3 DNA甲基化的阳性率(79.1%)明显高于癌旁组织(14.0%,P＜0.01);(2)食管鳞癌组织SOCS3 mRNA相对表达强度比值(0.53±0.30)明显低于癌旁组织(1.15±0.44,P＜0.01),食管鳞癌组织中甲基化组的SOCS3 mRNA表达(0.45±0.24)显著低于非甲基化组(0.86±0.29,P＜0.05);(3)食管鳞癌组织SOCS3蛋白表达(1.66±0.22)显著低于癌旁组织(1.83±0.15,P＜0.01),食管鳞癌组织中甲基化组SOCS3蛋白表达(1.61±0.21)显著低于非甲基化组(1.87±0.15,P＜0.01);(4)在TNM分期中Ⅲ期组表达均低于Ⅰ～Ⅱ期组(P＜0.05),伴有淋巴结转移组表达也都低于无淋巴结转移组(P＜0.05),未发现其在性别、年龄、家族史、吸烟史中有明显差异(P＞0.05);(5)食管鳞癌组织中SOCS3mRNA表达及其蛋白表达水平与肿瘤分化级别呈正相关(0.301＜r＜1,P＜0.05),与TNM分期、淋巴结转移呈负相关(-1＜r＜-0.301,P＜0.05).结论 食管鳞癌组织中SOCS3 DNA甲基化阳性率高,导致SOCS3基因表达下调,与食管鳞癌的分化、浸润和转移密切相关.     

STAT3及其磷酸化在食管鳞癌组织中的表达及其意义

目的 检测食管鳞癌组织中信号转导子和转录激活子3( STAT3)在mRNA、蛋白质和蛋白质磷酸化3种水平的表达,探讨其在食管鳞癌发生、发展、浸润、转移中的作用。方法 检测43例食管鳞癌组织中的STAT3 mRNA、STAT3和磷酸化STAT3( pSTAT3)的表达,并与相应癌旁正常食管组织作对照研究,分析STAT3 mRNA、STAT3和pSTAT3的表达与临床病理参数的关系。结果 43例实验样本中(1)食管鳞癌组织中STAT3 mRNA相对表达强度比值(1.43±0.59)较癌旁组织的比值(0.98±0.47)明显增高(P＜0.05);(2)食管鳞癌组织中STAT3、pSTAT3表达(2.16±0.39、1.40±0.15)也都显著高于癌旁组织(1.87±0.29、1.25±0.13,P＜0.05);(3)食管鳞癌组织中STAT3mRNA、STAT3和pSTAT3在肿瘤不同分化级别中表达差异有统计学意义,分化级别越低,表达水平越高(P＜0.05),并与肿瘤分化级别呈负相关(-1 ＜r＜-0.301,P＜0.05);它们在TNM分期中Ⅲ期组的表达均高于Ⅰ～Ⅱ期组(P＜0.05),伴有淋巴结转移组表达也都高于无淋巴结转移组(P＜0.05),并与两者呈正相关(两者均为0.301 ＜r＜1,P＜0.05);但未发现它们在性别、年龄、家族史、吸烟史中差异有统计学意义(P＞0.05)。结论 食管鳞癌组织中STAT3磷酸化异常激活后,导致STAT3mRNA、STAT3和pSTAT3的高表达,与食管鳞癌的分化、浸润、转移相关。     

血管内皮生长因子-C蛋白和mRNA在胆管癌中的表达及其意义

目的 检测胆管癌和癌旁0.5 cm胆管组织及手术切缘的正常胆管组织血管内皮生长因子(VEGF)-C蛋白及mRNA的表达,探讨其在胆管癌发生发展中的作用.方法 应用免疫组织化学过氧化物酶标记链霉卵白素法(SP)检测42例胆管癌组织及20例正常组织中VEGF-C蛋白的表达,同时应用逆转录-聚合酶链反应(RT-PCR)技术检测42例术中所取的新鲜的胆管癌、17例同个体癌旁胆管黏膜和20例正常胆管组织中VEGF-C的mRNA表达,并与临床资料进行相关分析.结果 正常胆管组织、癌旁组织、胆管癌组织中VEGF-C mRNA相对表达量分别0.6105±0.0577、0.6270 ±0.0664、0.6930±0.1078,VEGF-C mRNA在3组之间表达呈上升趋势(P＜0.05).VEGF-C蛋白表达趋势同其相对应的基因表达趋势一致,即VEGF-C mRNA在胆管癌组织中高表达(P＜0.05).胆管癌组织、正常胆管组织中VEGF-C表达的阳性率分别为83.33%和30.00%.结论 VEGF-C基因转录和蛋白可能参与了胆管癌的发生发展过程.     

EphA7基因在原发性肝细胞癌中的表达及其临床意义

目的 探讨原发性肝细胞癌中EphA7 mRNA的表达及其临床意义.方法 应用逆转录-聚合酶链反应(RT-PCR)及实时荧光定量PCR法检测EphA7 mRNA在40例肝癌及相应的癌旁肝组织和10例正常肝组织中的表达,并分析其与肝癌临床病理因素之间的关系.结果 40例肝癌组织及相应的癌旁肝组织和10例正常肝组织中均有EphA7 mRNA的表达.实时荧光定量PCR分析显示EphA7 mRNA在肝癌组织(20.0711±32.0232)中的表达显著高于癌旁肝组织(4.5184±9.4738,P＜0.05)和正常肝组织(4.1764±4.7193,P＜0.05),而在癌旁肝组织和正常肝组织中的表达差异无统计学意义(P＞0.05).EphA7 mRNA的过表达与肝癌细胞的分化程度、门静脉癌栓的形成及淋巴结转移等临床病理因素有关(P＜0.05).结论 EphA7的过表达与原发性肝细胞癌的生物学行为密切相关,可能在肝癌的恶性转化、侵袭和转移过程中发挥作用.     

CD105和细胞周期蛋白D1协同表达与食管鳞癌淋巴结转移及预后的关系

目的 探讨食管鳞癌中CD105和细胞周期蛋白D1(cyclin D1)的协同表达与淋巴结转移和预后的关系.方法 应用免疫组织化学方法检测南通市第一人民医院收治的80例食管鳞癌患者食管鳞癌组织中CD105和cyclin D1的表达,分析两者协同表达与食管鳞癌淋巴结转移及预后的关系.选取80例正常食管组织作对照.采用方差分析或t检验、x2检验、Pearson相关分析,生存分析采用Kaplan-Meier法,CD105的表达用微血管密度(MVD)值以-x±s表示.结果 食管鳞癌组织和正常食管组织CD105表达分别为36±8和11±3;Cyclin D1阳性表达率分别为61%(49/80)和23%(18/80),两者比较,差异有统计学意义(t=25.129,x2=4.972,P<0.05).按照食管鳞癌中CD105标记的MVD均值36为界,分为LCD105(MVD≤36)和HCD105(MVD＞36),其中LCD 44例,HCD 36例.LCD105淋巴结转移9例,HCD淋巴结转移26例.Cyclin D1阳性表达者有淋巴结转移28例,阴性表达者淋巴结转移7例.经Pearson列联相关分析显示CD105高表达、cyclin D1阳性表达与淋巴结转移有关(x2=21.562,9.217,P<0.05).HCD105+cyclin D1阳性28例,生存时间为(31±6)个月;LCD105+cyclin D1阳性21例,生存时间为(47±7)个月;HCD105+cyclin D1阴性8例,生存时间为(51±9)个月;LCD105+cyclin D1阴性23例,生存时间为(61±5)个月,4者比较,差异有统计学意义(F=11.76,P<0.05).结论 CD105和cyclin D1两者协同表达可作为判断食管鳞癌预后的指标.     

TMSG-1在人前列腺癌细胞株与前列腺癌组织中的表达及临床意义

目的 探讨肿瘤转移抑制基因-1(TMSG-1,亦称LASS2)在人不同转移潜能前列腺癌细胞株中与前列腺癌组织中的表达及其临床意义.方法 采用实时荧光定量聚合酶链反应(PCR)及细胞爬片免疫荧光组织化学方法,检测TMSG-1在人不同转移潜能前列腺癌细胞株低转移潜能(PC-3M-2134)和高转移潜能(PC-3M-IE8)中的表达.并采用免疫组织化学方法检测TMSG-1在人前列腺增生及前列腺癌组织中的表达,同时探讨其与临床病理特征之间的关系.结果 TMSG-1在PC-3M-284细胞株中的mRNA及蛋白表达(2.70±0.30、75.26±2.68)均明显高于在PC-3M-IE8细胞株中的表达(1.10±0.20、38.08±1.84),差异有统计学意义(P＜0.05).通过免疫组织化学观察表明TMSG-1在前列腺增生及前列腺癌组织中均有表达,但在前列腺增生中的阳性表达率(32/40)明显高于在前列腺癌中的阳性表达率(21/60).两者差异有统计学意义(P＜0.05).并且TMSG-1在前列腺癌组织中的表达与年龄、Gleason分级、淋巴结转移及TNM分期密切相关(P＜0.05),而与肿瘤的大小无明显相关.结论 TMSG-1在低转移潜能前列腺癌细胞株中的mRNA及蛋白表达明显高于在高转移潜能前列腺癌细胞株中的表达,证明它是一种肿瘤转移抑制基因.TMSG-1在人前列腺增生与前列腺癌组织中的表达之间差异有统计学意义,并且TMSG-1在前列腺癌中的表达与年龄、Gleason分级、淋巴结转移及TNM分期密切相关.

Abstract：

Objective To investigate the expression of tumor metastasis suppressor gene 1 (TMSG-1 as well LASS2) in different prostate cancer cell lines and prostate cancer tissues and its clinical significance. Methods Sixty patients with prostate cancer had undergone surgery between 2008 and 2010.Forty patients with prostatic hyperplasia were chosen. Immunofluorescence histochemistry was used to study the distribution of TMSG-1 in cells, immunohistochemistry was used to observe the difference in TMSG-1 expression between prostatic hyperplasia and prostate cancer tissues, and the relationship between the TMSG-1 expression and clinicopathological features in prostate cancer tissues was analyzed. Results The level of TMSG-1 mRNA in PC-3M-2B4 cell line with low metastatic potentiality (2. 70 ±0. 30) was higher than in PC-3M-IE8 cell line (1. 10 ±0. 20). Immunofluorescence histochemistry revealed that most of the collected prostate cancers and prostatic hyperplasia tissues expressed TMSG-1 in cytoplasma, and nuclei were stained in a few of prostate cancer tissues. The average fluorescence intensity of TMSG-1 in PC-3M-2B4 cells (75. 26 ±2. 68) was obviously higher than in PC-3M-IE8 cells (38. 08 ± 1. 84). There was obviously different expression of TMSG-1 between prostate cancers (21/60) and prostatic hyperplasia ( 32/40 ) ( P ＜0. 05 ) . The TMSG-1 levels in prostate cancer tissue were significantly correlated with ages,Gleason grade, lymph node metastasis and tumor, nodes, metastasis (TNM) staging (P ＜0. 05) , but not with the size of tumor. Conclusion The expression level of TMSG-1 mRNA and protein in prostate cancer cell lines with low metastatic potentials significantly higher than in prostate carcinoma cell lines with high metastatic potentials, which proves that TMSG-1 is a tumor metastasis suppressor gene. From the difference in the TMSG-1 expression between human prostatic hyperplasia and prostate cancer tissues and the correlation with age, Gleason grade, lymph node metastasis and TNM stage in prostate cancers, we infer that TMSG-1 is an important prognostic indicator in judging prostate cancer cell growth, progression and metastasis.