钙结合蛋白S100A4与消化系肿瘤研究进展

S100A4基因编码的钙离子结合调节蛋白-S100A4蛋白,通过与钙离子结合,在许多肿瘤发展、转移过程中发挥重要作用.目前研究认为其与肿瘤的浸润和转移密切相关.本文就S100A4生物学特性及其在消化系肿瘤中作用及可能机制的研究进展作一综述.     

血清S100B、S100A6、S100P水平升高与急性冠脉综合征的相关性研究

目的:探讨血清终末糖基化产物受体(RAGE)的配基S100B、S100A6、S100P水平与急性冠脉综合征(ACS)相关性。方法:连续收集882例冠状动脉造影患者,检测血清S100B、S100A6、S100P、游离RAGE(sRAGE)、肿瘤坏死因子(TNF)-α水平;根据临床表现及实验室资料,将患者分为对照组(n=251)、稳定型心绞痛(SA)组(n=211)及ACS组(n=420)。结果:ACS组血清S100B、S100A6、S100P和TNF-α水平[(103.73±56.90)ng/L、(5.28±4.15)μg/L、(8.73±7.96)μg/L、(87.82±39.30)ng/L]均显著高于SA组[(81.93±27.65)ng/L、(4.36±2.45)μg/L、(3.41±3.08)μg/L、(71.88±30.70)ng/L]和对照组[(78.00±22.71)ng/L、(3.97±2.57)μg/L、(3.38±2.74)μg/L、(57.07±27.23)ng/L,P0.01];ACS组血清sRAGE水平高于对照组[(724.01±320.37)ng/L对(652.55±351.24)ng/L,P0.01]。进一步将ACS组分为ST段抬高型心肌梗死(STEMI)和不稳定型心绞痛/非ST段抬高型心肌梗死(UA/NSTEMI)2个亚组进行分析,STEMI亚组的S100B、S100A6、S100P水平高于UA/NSTEMI亚组;ACS组血清S100B水平与肌钙蛋白I(cTnI)峰值水平相关(P0.05),血清S100P水平与肌酸激酶同工酶(CK-MB)及cTnI峰值水平均有相关性(P0.01)。多元回归分析发现,S100B、S100A6、S100P和传统危险因素均与ACS发病相关。结论:血清S100B、S100A6、S100P水平与ACS相关,与心肌缺血的损伤程度相关,它们在ACS的病理生理过程中发挥重要作用。     

Bmi-1和S100A4蛋白在食管鳞状细胞癌中的表达及其临床病理意义

目的:探讨Bmi-1和S100A4蛋白在食管鳞状细胞癌(ESCC)组织中的表达及其临床病理意义.方法:采用免疫组织化学法分别检测68例食管鳞状细胞癌、45例癌旁异型增生及36例正常食管黏膜组织中Bmi-1及S100A4蛋白的表达,并分析两者的表达水平与临床病理因素的关系.采用X2检验进行统计学分析.结果:Bmi-1蛋白在食管鳞状细胞癌、癌旁异型增生及正常黏膜组织中的阳性表达率分别为57.4%、48.9%、25.0%;S100A4蛋白的阳性表达率分别为48.6%、26.7%、13.9%,两者在组间的表达差异有统计学意义(P<0.01).食管鳞癌组织中Bmi-1和S100A4的蛋白表达与淋巴结转移及TNM分期均密切有关(P<0.05),而S100A4的蛋白表达还与肿瘤浸润深度有关(P<0.05).两者在食管鳞状细胞癌组织中的表达呈正相关(r=0.302,P<0.05).结论:Bmi-1及S100A4的蛋白表达与食管鳞状细胞癌发生发展密切相关,联合检测Bmi-1及S100A4两蛋白指标对食管鳞癌的预后判断具有重要的意义.     

EF手型钙结合蛋白S100A6及其与肿瘤关系的研究进展

S100A6蛋白是一类具有EF手型模序结构的钙结合蛋白,通过对钙离子的调节及与靶蛋白的相互作用,启动细胞信号转导,参与细胞生长、分化、细胞周期及胞外基质分泌等多种生物学过程,与肿瘤发生、发展及转移预后相关.本文就近年来S100A6钙结合蛋白的研究现状与进展进行综述.     

S100A8和S100A9在冠心病中的研究进展

S100A8和S100A9作为内源性危险相关分子模式与Toll样受体4和晚期糖基化终产物受体相识别,通过参与免疫应答,改变内皮通透性并促进斑块内炎症,从而影响动脉粥样硬化的发生和发展.此外,S100A8和S100A9血浆水平升高与增加心血管事件的风险密切相关.本文综述S100A8和S100A9的研究现状及其在冠心病的预...     

靶向S100A4的shRNA对乳腺癌MCF-7细胞体外侵袭力及迁移力的影响

目的探讨靶向S100A4短发夹RNA（shRNA）对MCF-7细胞侵袭力和迁移力影响的作用机制。方法构建S100A4基因特异性shRNA表达载体,使用QRT-PCR和Westernblot检测转染后MCF-7细胞中s100A4的表达水平,经过脂质体介导将S100A4-shRNA表达载体转染人MCF-7细胞,G418筛选及克隆化培养。采用Trans-well小室法和划痕试验检测MCF-7细胞侵袭力和迁移力变化。结果经测序鉴定证实S100A4-shRNA表达载体成功构建。转染48h后,所构建的S100A4-shRNA-1表达载体能有效抑制MCF-7细胞中S100A4表达;MCF-7细胞形态无显著变化,但侵袭力和迁移力明显下降。结论S100A4在乳腺癌细胞侵袭和转移过程中扮演重要角色,通过沉默其表达可抑制MCF-7的侵袭力和迁移力从而抑制其转移。     

乙型肝炎病毒对于S100 A11信号转导影响的研究

S10 0A11是具有EF 手型 (EF handtype)结构的Ca2 +调节蛋白 (Ca2 + modulatedprotein)多基因家族的一个成员 ,与钙结合之后 ,蛋白的构象发生改变 ,暴露出疏水区 ,然后与靶蛋白结合。Rintala等[1] 认为S10 0A11的生理学功能属于附加素Ⅰ (annexinⅠ )家族。Tanaka等[2 ] 以COLO 2 0 5细胞建立cDNA文库 ,随机挑选 10 5 6个克隆进行测序 ,38.4 % (2 0 2 / 5 2 6 )的基因与GenBank中的基因序列有 80 %以上的同源性。包括人的钙囊素 (calgizzarin)基因 ,与兔钙囊素的基因序列高度同源 ,在各种不同的细胞系中均有表达。我们的研究表明 ,…     

非小细胞肺癌患者S100A4蛋白表达及其临床意义

目的探讨非小细胞肺癌S100A4蛋白的表达及临床意义。方法选择130例非小细胞肺癌患者术后癌组织标本,用免疫组织化学S-P方法,检测NSCLC中的S100A4蛋白含量并进行统计学分析。结果在NSCLC中S100A4蛋白阳性率为69．2％;鳞状细胞癌、腺癌、腺鳞癌、大细胞肺癌阳性率分别为62．7％、68．1％、70．O％、100％;S100A4蛋白表达阳性表达与年龄、淋巴结转移、远处转移及TNM临床分期明显相关;S100A4蛋白阳性组和阴性组3年生存率比较有显著差异（P〈0．05）。结论S100A4蛋白的表达和与年龄、淋巴转移、临床分期及预后有密切相关;可作为肺癌早期的标记物。     

胰腺癌S100A4癌基因及ppENK抑癌基因的甲基化状态

目的 分析胰腺癌及胰腺癌细胞株ppENK、S100A4基因的甲基化状态.方法 收集31例胰腺癌及相应癌旁组织、5株胰腺癌细胞株及1例正常胰腺组织.采用MSP方法分析ppENK基因甲基化状态,采用COBRA方法分析S100A4基因甲基化状态,RT-PCR检测ppENK和S100A4 mRNA,免疫组化法检测S100A4蛋白表达,并与胰腺癌临床参数进行相关性分析.结果 正常胰腺组织ppENK基因无甲基化,S100A4基因高甲基化.31例胰腺癌组织中ppENK基因甲基化率为90.3%,与临床参数无相关性;S100A4基因低甲基化率为71.0%,仅与外周血CA19-9水平呈相关性(P=0.011,OR=0.05).S100A4蛋白在胰腺癌组织中表达率为87.1%,该表达与S100A4基因低甲基化相关(P=0.017),同时与肿瘤的分化程度有关,肿瘤分化程度越低,表达阳性率越高.S100A4基因低甲基化与ppENK基因甲基化相关(P=0.019).5株胰腺癌细胞株ppENK基因均甲基化,ppENK mRNA不表达;S100A4基因均低甲基化,S100A4 mRNA均高表达.结论 胰腺癌组织ppENK基因为高甲基化状态,而S100A4基因为低甲基化状态.     

Colorectal cancer progression correlates with upregulation of S100A11 expression in tumor tissues

Background and aims Early detection and treatment of human colorectal cancers remain a challenge. Identification of new potential markers may help in the diagnosis of colorectal cancer. Materials and methods By comparative two-dimensional gel electrophoresis using extracts from colorectal tumor and adjacent normal tissues, we identified a calcium-binding protein, S100A11, which was highly expressed in colorectal cancer compared with adjacent normal tissues. We expanded our study in 89 clinical colorectal tumor samples to validate this finding and correlates S100A11 expression in human colorectal cancer tissues with various stages of the tumor by Western blotting and immunohistochemical staining. Results We identified a calcium-binding protein, S100A11, which was highly expressed in colorectal cancer compared with adjacent normal tissues. S100A protein was expressed predominantly in the cytoplasm of normal tissue; however, it was expressed in both the nuclei and cytoplasm of colorectal cancer. S100A11 level in colorectal cancer tissue was increased following stage progression of the disease. Conclusion These findings suggest S100A11 could be helpful in the pathological study of colorectal cancer, especially for the classification of different stages in colorectal cancer.     

膀胱移行细胞癌组织中S100A4、MMP-2的表达及意义

目的探讨S100A4和基质金属蛋白酶-2（MMP-2）在膀胱移行细胞癌（TCCB）组织中的表达及其与肿瘤浸润、转移的关系。方法用免疫组化SP法检测癌组织中的S100A4和MMP-2。结果S100A4及MMP-2在TC-CB组织中的阳性表达率分别为60%和55%,而正常组织中未见表达或微量表达;两者在癌组织中的表达与肿瘤浸润深度及分级有关（P均〈0.01）,S100A4与MMP-2的表达有关（r=0.66,P〈0.01）。结论S100A4与MMP-2在TCCB中的表达增加,其过量表达与TCCB浸润转移相关。     

沉默人胰腺癌细胞S100A4基因表达对肿瘤相关基因mRNA表达的影响

目的 观察沉默S100A4基因表达对人胰腺癌BxPC-3、AsPC-1细胞肿瘤相关基因COX-2、bcl-2 、Surviving、MMP-9 mRNA表达的影响,探讨它们之间的关系.方法 应用靶向S100A4的小干扰RNA(siRNA)转染人胰腺癌BxPC-3、AsPC-I细胞,应用无同源性的siRNA-C转染细胞作为阴性对照,以未转染细胞作为对照组.采用RT-PCR检测干扰后细胞S100A4、COX-2、Survivin、MMP-9、bcl-2 mRNA的表达.结果 人胰腺癌BxPC-3细胞的对照组、siRNA-C组、siRNA-S100A4组的S100A mRNA表达量分别为0.661 ±0.023、0.659±0.043、0.379±0.039;COX-2 mRNA表达量分别为0.760±0.026、0.830±0.017、0.443±0.006;Survivin mRNA表达量分别为0.948±0.049、0.909±0.081、0.068 ±0.006;bcl-2mRNA表达量分别为0.462±0.018、0.421±0.049、0.184±0.025;MMP-9 mRNA表达量分别为0.813±0.008、0.908±0.063、0.246±0.027.AsPC-I细胞的对照组、siRNA-C组、siRNA-S100A4组的S100A4mRNA表达量分别为0.641±0.042、0.626±0.053、0.320±0.081;COX-2 mRNA表达量分别为0.727±0.021、0.743±0.025、0.560±0.035;Survivin mRNA表达量分别为0.994±0.032、0.984±0.049、0.063±0.005;bcl-2 mRNA表达量分别为0.458±0.004、0.537±0.046、0.181±0.007;MMP-9 mRNA表达量分别为0.698±0.011、0.718±0.073、0.199±0.013.2株细胞的siRNA-S100A4组的S100A、COX-2、Survivin、bcl-2、MMP-9 mRNA表达量均较其相应的siRNA-C组及对照组显著减少(P值均＜0.01),而siRNA-C组与对照组间的表达量差异无统计学意义.结论 S100A4通过上调COX-2、Survivin、bcl-2、MMP-9基因的表达在胰腺癌发生、发展中发挥作用.     

Expression and clinical significance of S100A2 and p63 in esophageal carcinoma

AIM： TO investigate the expression and clinical significance of S100A2 mRNA and protein, p63 protein in esophageal squamous cell carcinoma （ESCC） and their roles in carcinogenesis and progression of esophageal carcinoma （EC）. METHODS： Immunohistochemical staining （S-P method） for S100A2 and p63 protein were performed in 40 samples of ESCC and 40 samples of normal esophageal mucosa. In situ hybridization （ISH） was used to detect the expression of S100A2 mRNA. RESULTS： Expression of S100A2 mRNA in ESCC was positive in 77.5% of samples, which was lower than that in normal mucosa （100%） by ISH （P = 0.002）. The expression level of S100A2 mRNA was closely related to differentiation and and node-metastasis （P = 0.012, P = 0.008）. Expression of $100A2 protein was positive in 72.5% of ESCC samples and expression of p63 protein was positive in 37.5% of ESCC samples, and was lower than that in normal mucosa （100%） （P = 0.000）. The expression of S100A2 protein was correlated with the differentiation and node-metastasis （P = 0.007, P = 0.001）, but no relationship was observed between the expression of p63 protein and clinical pathological manifestations. S100A2 protein was positively correlated with the expression of S100A2 mRNA, and negatively associated with the expression of p63 protein （P = 0.000, P = 0.002）. CONCLUSION： S100A2 and p63 protein both play important roles in the carcinogenesis of ESCC. An investigation into the combined expression of S100A2 and p63 may be helpful in early diagnosis and in evaluating the prognosis of ESCC.     

Overexpression of S100A4 is closely associated with progression of colorectal cancer

AIM: To investigate whether S100A4 played an important role in the development or progression of colorectal cancer. METHODS: A total of 124 colorectal adenocarcinoma tissue specimens were analyzed by immunohistochemistry for the expression of S100A4 protein and subsequently investigated for the gene mutations in the coding region of S100A4 gene. The specimens were collected over a 3-year period in the laboratories at our large teaching hospital in Seoul, Republic of Korea. RESULTS: Normal colonic epithelium either failed to express or showed focal weak expression of S100A4. Moderate to strong cytoplasmic expression of S100A4 was seen in 69 (55.6%) of the 124 colorectal carcinoma tissue specimens. S100A4 expression was detected in 43 (69.4%) of 62 specimens with lymph node metastasis. Statistically, overexpression of S100A4 was significantly associated with Dukes' stage and lymph node metastasis. Nuclear staining was also observed in 24 (19.4%) of 124 samples and dosely associated with Dukes' stage. However, there was no significant correlation between overexpression of S100A4 and other investigated clinico-pathologic parameters, including tumor localization, tumor size, and survival period. In mutational analysis, no gene mutation was found in the analyzed genomic area of colorectal cancer. CONCLUSION: Overexpression of S100A4 may be closely related with the aggressiveness of colorectal carcinoma.     

The value of mRNA expression of S100A8 and S100A9 as blood-based biomarkers of inflammatory bowel disease

Background and study aimsNon-invasive biomarkers of inflammatory bowel diseases (IBD) are of critical importance. Here, we evaluated the S100A8 and S100A9 mRNA expression, as the heterodimers of calprotectin, in the blood leucocytes of IBD patients to find how their expression associates with the disease characteristics.Patients and methodsIn this cross-sectional study, 59 IBD patients and 30 healthy subjects were included. The flare and remission phases of disease were identified in 46 and 13 patients, respectively. Blood leucocytes were isolated, and the S100A8 and S100A9 mRNA expression were evaluated in the isolated leucocytes using relative quantification real-time PCR.ResultsThe mean S100A8 and S100A9 mRNA expression were significantly higher in IBD patients than in the controls (p = 0.03 and p = 0.02, respectively). The mean S100A8 and S100A9 mRNA expression were significantly higher in the flare phase of the disease compared with the remission phase (p = 0.01 and p = 0.007, respectively). S100A8 distinguished IBD patients from controls with the sensitivity and specificity of 73% and 64%, and flare phase of disease from remission with the sensitivity and specificity of 67% and 62%. On the other hand, S100A9 distinguished IBD patients from controls with the sensitivity and specificity of 81% and 70%, and flare phase of disease from remission with the sensitivity and specificity of 68% and 64%.ConclusionThe S100A8 and S100A9 mRNA are differentially expressed in blood leucocytes of IBD patients compared to healthy controls as well as active versus quiescent disease. Thus, they can be potentially used as a blood-based biomarker in the monitoring of IBD.     

Expression of protein S100A4 is a predictor of recurrence in colorectal cancer

AIM: To investigate the prognostic significance of S100A4 expression in colorectal cancer and its correlation with expression of E-cadherin and p53. METHODS: A cohort of archival formalin-fixed paraff inembedded specimens was selected from 127 patients with colorectal cancer who underwent surgical resection between April 2000 and March 2004 at the Department of Surgery, Korea University Guro Hospital. The expression of protein S100A4 was evaluated according to the proportion of positively stained cancer cel...     

S100A4蛋白在肺癌中的表达及其临床意义

目的探讨S100A4蛋白在肺癌组织中的表达,并探讨其临床意义。方法搜集45例肺鳞癌、50例腺癌、23例小细胞肺癌病例,调查其分化程度、肿瘤大小、淋巴结转移及临床分期等参数;采用免疫组化SP法分别检测各型肺癌组织及癌旁组织中S100A4蛋白的表达,应用Image-Pro Plus 6.0软件进行图像分析。结果所有肺鳞癌、腺癌标本中S100A4蛋白的表达均强于相应的癌旁组织,组间比较差异有统计学意义(P0.01)。小细胞肺癌细胞内未检测到S100A4的表达,但在其间质血管中检测到S100A4的表达。在鳞癌患者中的S100A4蛋白表达中,Ⅰ期IOD值为19012.12±4856.98,Ⅱ期为27654.40±5365.86,Ⅲ期为39001.38±6435.97,IV期为48753.00±7727.42(P0.05),而在腺癌中,Ⅰ期为22343.11±5156.18,Ⅱ期为31942.04±4915.36,Ⅲ期为44519.23±5435.07,Ⅳ期为51060.53±10757.74(P0.05)。鳞癌和腺癌标本中S100A4蛋白的表达有淋巴结转移组明显高于无淋巴结转移组(P0.05),有远处转移组明显高于无远处转移组(P0.05)。肺鳞癌、腺癌标本中S100A4蛋白的表达与患者的性别、年龄、肿瘤大小、肿瘤分化程度无关(P0.05)。结论 S100A4蛋白在非小细胞肺癌的增殖及转移中起重要作用,检测S100A4蛋白有助于非小细胞肺癌预后的判断;同时它可能在小细胞肺癌的侵袭转移中也起到一定作用。