Notch1受体在乳腺癌组织中的表达及其与临床病理特征的关系

目的 探讨Notch1受体与乳腺癌患者的临床病理特征及预后的关系.方法 应用免疫组化技术检测106例乳腺癌组织中Notch1受体、ER、PR、CerbB-2受体表达情况,分析其与临床病理特征及预后的相关性.结果 乳腺癌组织中Notch1受体表达明显高于癌旁正常组织(P＜0.05);Notch1受体表达与CerbB-2具有相关性(P＜0.05),与ER、PR无显著相关性(P＞0.05);Notch1受体高表达组5年生存率低于低表达组(P＜0.05).结论 乳腺癌组织中Notch1受体表达明显高于癌旁正常组织;Notch1受体表达与CerbB-2具有相关性,推测Notch1受体可能与CerbB-2存在交互作用;Notch1受体高表达与预后不良有关.     

LOX与HIF-1α在非小细胞肺癌中表达增强

目的 研究赖氨酰氧化酶(LOX)与低氧诱导因子-1α(HIF-1α)在非小细胞肺癌(NSCLC)中表达情况及其临床意义.方法 收集临床NSCLC组织标本41例,用免疫组织化学染色法(IHC)检测NSCLC组织中LOX和HIF-1α蛋白表达;蛋白印迹法(Western blot)检测NSCLC组织及相应的癌旁组织、正常肺组织中LOX与HIF-1 α蛋白表达.结果 IHC结果显示LOX蛋白表达主要在细胞质,HIF-1α蛋白表达主要在细胞核.LOX与HIF-1 α在NSCLC组织中阳性表达率均明显高于正常肺组织(P ＜0.05);LOX蛋白的高表达与肿瘤的病理类型、分化程度、淋巴转移和临床分期之间存在显著相关(P ＜0.05);HIF-1α蛋白的高表达与肿瘤的病理类型、大小、淋巴转移和临床分期之间存在显著相关(P ＜0.05);LOX与HIF-1α蛋白在NSCLC组织中表达呈正相关性(P＜0.05).Western blot结果显示NSCLC组织中LOX与HIF-1α蛋白的表达显著高于相应的癌旁组织及正常肺组织(P＜0.05).结论 LOX与HIF-1α的异常表达可能与NSCLC发生、发展有关,并且LOX与HIF-1α的高表达可能协同促进了NSCLC的侵袭转移.     

乳腺癌中INHBA表达及与临床预后的关系

目的检测INHBA(inhibin-βA)在乳腺癌及癌旁乳腺组织中的表达,探讨其与乳腺癌临床病理特征的关系及对乳腺癌患者预后的意义。方法应用免疫组化法检测85例乳腺浸润性导管癌及35例癌旁乳腺组织中INHBA的表达。结果INHBA在乳腺癌和癌旁组织中的表达差异有统计学意义(P0.05)。INHBA高表达和肿瘤较低的分化程度、淋巴结转移及较高的Ki-67增殖指数具有相关性(P0.05)。INHBA高表达乳腺癌患者的生存期明显短于低表达组(P0.05)。多因素Cox比例风险回归模型分析显示,INHBA表达可以作为判断乳腺癌患者的独立危险因素(P0.05)。结论INHBA表达与肿瘤分化程度、淋巴结转移及Ki-67增殖指数密切相关,可能参与乳腺癌的发生发展,可以作为乳腺癌患者预后的判断指标。     

WNT5B在乳腺癌中的表达及意义

目的:研究WNT5B在乳腺癌中的表达,初步探讨WNT5B与乳腺癌临床病理特征的关系。方法:采用real-time PCR和Western blot法检测67例乳腺癌及癌旁组织中WNT5B在mRNA和蛋白水平的表达情况,通过免疫组织化学方法检测WNT5B在乳腺癌和癌旁组织中的表达并分析WNT5B的表达与相关临床病理指标之间的关系。结果:67例乳腺癌组织标本中均有不同程度WNT5B的mRNA及蛋白表达,且WNT5B在乳腺癌组织的表达明显低于癌旁组织(P0.05);其中WNT5B在原发性肿瘤大小T≤20 mm的乳腺癌患者中的表达明显高于其在T20 mm组患者中的表达(P0.05);WNT5B的表达与乳腺癌患者腋窝淋巴结转移情况、组织学分级、相关的免疫组织化学指标(ER、PR、c-Er Bb-2、p53和Ki-67)之间无明显的相关性(P0.05)。结论:WNT5B在乳腺癌组织中的表达低于癌旁组织,WNT5B表达与乳腺癌患者原发肿瘤大小呈负相关,提示WNT5B可能作为乳腺癌预后的一个新的分子标志物,为乳腺癌的诊治提供新的思路。     

Bim与BCSG1蛋白在乳腺癌中的表达及临床意义研究

目的 探究Bcl-2相互作用细胞凋亡调节因子(Bim)与乳腺癌特异性基因1(BCSG1)蛋白在乳腺癌中的表达及临床意义.方法 选取我院2015年1月至2017年2月期间收治的60例乳腺癌患者,通过外科手术收集60例患者乳腺癌组织以及癌旁组织,通过免疫组织化学染色检测两种组织中Bim与BCSG1蛋白表达情况,分析不同分期、不同分化程度、不同病理、不同直径和是否转移情况下Bim与BCSG1蛋白表达差异.结果 免疫组织化学染色结果显示:Bim与BCSG1在乳腺癌组织中高表达,而在癌旁组织中低表达,比较差异有统计学意义(P＜0.05);肿瘤直径≥4cm、低分化程度、浸润性乳腺癌、Ⅲ-Ⅳ期和远处转移的乳腺癌患者,Bim与BCSG1阳性率明显高于肿瘤直径＜4cm、高度分化、中度分化、非浸润性乳腺癌、Ⅰ-Ⅱ期和非转移的乳腺癌患者(P＜0.05).结论 Bim和BCSG1蛋白在乳腺癌组织中高表达,且表达水平与肿瘤大小、分期、浸润、分化程度和转移性密切相关.     

乳腺癌组织中SOX4、EZH2的表达及临床意义

目的观察上皮-间质转化(epithelial-mesenchymal transition,EMT)调控因子SOX4和EZH2在乳腺癌组织中的表达,探讨两者的临床意义。方法采用免疫组化En Vision两步法检测241例乳腺癌组织及126例癌旁非肿瘤乳腺组织中SOX4、EZH2的表达,分析两者表达的相关性及其与乳腺癌临床病理特征的关系。结果乳腺癌组织中SOX4的高表达率为82.2%,显著高于癌旁非肿瘤乳腺组织的高表达率(57.1%,P0.05);EZH2在乳腺癌组织中的高表达率为80.1%,显著高于癌旁非肿瘤乳腺组织的高表达率(47.6%,P0.05)。SOX4高表达与肿瘤淋巴结转移、TNM高分期、HER-2高表达相关(P0.05);EZH2高表达与肿瘤组织学高分级、淋巴结转移、ER阴性、EGFR阳性、Ki-67高增殖指数相关(P0.05),并与SOX4表达呈显著正相关(rs=0.256,P0.001)。结论 EMT调控因子SOX4和EZH2在乳腺癌组织中表达上调,两者可能共同参与乳腺癌的转移,有望成为预测乳腺癌转移的潜在生物学标志物。     

RIN1在人膀胱尿路上皮癌中的表达

目的研究RIN1在人膀胱尿路上皮癌中的表达。方法分别应用免疫蛋白印迹技术和实时定量PCR技术检测RIN1蛋白和RIN1 m RNA在人膀胱尿路上皮癌及癌旁组织中的表达。结果 Real-time PCR结果发现,在15对新鲜的膀胱尿路上皮癌及癌旁组织中,有12对的癌组织中RIN1表达高于癌旁组织。在膀胱尿路上皮癌组织中,RIN1的m RNA表达平均倍数为10.61±5.42,癌旁组织中,RIN1的m RNA平均倍数为4.31±1.77,P0.05。Western blot法结果认证了RIN1在膀胱尿路上皮癌组织中的表达是升高的。结论 RIN1在膀胱尿路上皮癌组织中的m RNA和蛋白的表达水平高于癌旁组织。     

肝细胞癌中HBO1和Ki-67表达的相关性及其临床意义

目的探讨HBO1和Ki-67在人肝细胞癌中表达的相关性及其临床意义。方法采用免疫组化En Vision法检测142例肝细胞癌及对应癌旁组织中HBO1和Ki-67的表达,分析两者表达的相关性及其与临床病理特征和预后的关系。结果肝细胞癌组织中HBO1和Ki-67的阳性率分别为69.0%(98/142)和55.6%(79/142),明显高于癌旁组织24.6%(35/142)和19.7%(28/142),差异有统计学意义(P0.05);两者的表达呈明显正相关(r_s=0.505,P0.05);HBO1和Ki-67高表达均与肿瘤大小、分化程度、TNM分期及门静脉癌栓密切相关(P0.05);Kaplan-Meier生存分析显示,HBO1、Ki-67高表达组患者的生存时间明显低于低表达组(P0.05);Cox多因素分析显示,患者预后与HBO1高表达、Ki-67高表达、TNM分期及门静脉癌栓显著相关(P0.05)。结论 HBO1和Ki-67表达与肝细胞癌的发展关系密切相关,两者联合检测可以用于预测肝细胞癌的恶性程度和预后的评估。     

VEGF、HIF-1α在乳腺癌患者组织中的表达及临床意义

目的:分析血管内皮生长因子(Vascular endothelial growth factor,VEGF)、缺氧诱导因子-1α(Hypoxia inducible factor-1 α,HIF-1α)在乳腺癌患者组织中的表达及临床意义.方法:收集2018年9月至2021年3月于本院经病理组织确诊的78例乳腺癌患者组织标本及其癌旁正常乳腺组织标本资料.采用免疫组织化学染色法检测病灶组织及癌旁正常乳腺组织中VEGF、HIF-1α蛋白表达情况,记录患者临床特征.对比乳腺癌患者的病灶组织与癌旁正常乳腺组织中VEGF、HIF-1α蛋白阳性表达率;分析对比不同临床特征的乳腺癌患者病灶组织中VEGF、HIF-1α蛋白阳性表达情况;病灶组织中VEGF、HIF-1 α蛋白阳性表达对乳腺癌患者淋巴结转移的评估价值.结果:病灶组织中VEGF、HIF-1α蛋白阳性表达率均高于癌旁正常乳腺组织(P＜0.05);有淋巴结转移的患者病灶组织中VEGF、HIF-1α蛋白阳性表达率高于无淋巴结转移的患者(P＜0.05);病灶组织中VEGF、HIF-1α蛋白对乳腺癌患者淋巴结转移评估价值的AUC分别为0.723、0.727,均有一定评估价值.结论:VEGF、HIF-1α蛋白在乳腺癌组织中阳性表达率较高,检测病灶组织中VEGF、HIF-1α蛋白阳性表达有助于评估患者淋巴结转移情况     

葡萄糖转运蛋白1在乳腺癌组织中表达的临床意义

目的 探讨葡萄糖转运蛋白1(glucose transporter 1,Glut-1)及其mRNA在正常乳腺组织、乳腺纤维腺病、乳腺纤维腺瘤和乳腺癌中的表达及其意义.方法 收集乳腺组织标本147例,其中乳腺浸润性导管癌92例、纤维腺瘤26例、腺病24例、正常乳腺组织5例,应用免疫组织化学EnVision法、Western blot以及RT-PCR分别定量检测不同病变组织中Glut-1蛋白及其mRNA表达水平.结果 在正常乳腺组织、乳腺腺病以及纤维腺瘤组织中难以检测到Glut-1阳性表达或仅呈轻微胞质着色.在乳腺癌组织中,Glut-1表达强度明显增高(P=0.0002),主要定位于瘤细胞膜,细胞质染色较淡.原发灶及转移灶中央的细胞Glut-1表达明显高于周边癌组织,转移灶Glut-1表达水平明显高于原发灶,浸润癌高于原位癌.Western blot定量分析结果显示,乳腺癌组织中Glut-1表达水平显著高于纤维腺瘤(P=0.001)和腺病(P=0.001),各病变组织间差异有统计学意义(P=0.0002).RT-PCR定量检测分析显示乳腺浸润性导管癌中Glut-1 mRNA的表达明显高于纤维腺瘤(P＜0.05)和腺病(P＜0.05),各病变组织间差异有统计学意义(P=0.0001).结论 乳腺癌组织中葡萄糖转运活性显著增高,Glut-1的表达水平与乳腺肿瘤的恶性程度、肿瘤细胞的浸润与转移密切相关;Glut-1高表达可作为细胞的恶性转化标志,并有望成为乳腺恶性肿瘤早期诊断、判断预后的一种新标记物及治疗的新靶点.     

Prognostic significance of RIN1 gene expression in human non-small cell lung cancer

Ras interaction/interference 1 (RIN1), originally identified as a Ras effector protein, has been implicated in tumorigenesis and development of human cancers. The aim of this study was to detect RIN1 expression in human non-small cell lung cancer (NSCLC) and to analyze its association with prognosis of NSCLC patients. Quantitative real-time RT-PCR was performed to examine the expression of RIN1 mRNA in 25 cases of NSCLC and corresponding non-tumor tissue samples. Immunohistochemistry was performed to detect the expression of RIN1 in 90 NSCLC tissues. We found that the expression levels of RIN1 mRNA in NSCLC tissues were significantly higher than those in corresponding non-tumor tissues. High-level RIN1 expression was observed in 53.3% (48 of 90 cases), and correlated with poor tumor differentiation (P = 0.024), TNM stage (P = 0.032), and lymph node metastasis (P = 0.018). Patients with high expression levels of RIN1 showed lower overall survival rate than those with low expression levels (P = 0.033). Multivariate analysis showed that high RIN1 protein expression was an independent prognostic factor for NSCLC patients (P = 0.021). Our study suggests that over-expression of RIN1 may play an important role in the progression of NSCLC and RIN1 expression may offer a valuable marker for predicting the outcome of patients with NSCLC.     

ACTL8的表达与乳腺癌临床病理特征及预后的关系

目的:探讨肌动蛋白样蛋白8(ACTL8)在乳腺癌中的表达及其与乳腺癌临床病理特征及预后的关系。方法:采用Western blot方法检测人正常乳腺上皮细胞株MCF-10A和5种乳腺癌细胞株中ACTL8蛋白的表达;采用免疫组织化学方法检测6例乳腺癌标本及其对应的癌旁组织中ACTL8蛋白的表达;收集TCGA乳腺癌数据集,将488例乳腺标本纳入,分析ACTL8的mRNA表达水平与乳腺癌患者临床病理特征及预后的关系。结果:ACTL8蛋白在乳腺癌细胞株T47D、BT474、HCC1954和SKBR3中表达显著高于乳腺上皮细胞株MCF-10A;ACTL8蛋白在乳腺癌组织中的表达也显著高于癌旁组织;ACTL8 mRNA表达与乳腺癌患者年龄、肿瘤大小、临床TNM分期和淋巴结转移相关(P0.05)。ACTL8 mRNA高表达的乳腺癌患者5年内生存率低、预后差。结论:ACTL8在乳腺癌组织中高表达并与乳腺癌临床病理特征及预后密切相关,提示ACTL8可作为判断乳腺癌预后的标志物。     

Carboxypeptidase A4 negatively correlates with p53 expression and regulates the stemness of breast cancer cells

Background: Triple-negative breast cancer (TNBC) is an aggressive cancer subtype lacking effective treatment options, and p53 is the most frequently mutated or deleted gene. Carboxypeptidase A4 (CPA4) is an extracellular metallocarboxypeptidase, which was closely associated with aggressiveness. Although a recent study indicated that CPA4 could induce epithelial‑mesenchymal transition in breast cancer cells, no studies investigated its stemness-related function and the correlation between CPA4 and p53 in TNBC. In this study, we aimed to investigate the CPA4 levels in breast cancer tissues and analyze its association with p53, and study its roles in cancer stemness maintenance.Methods: CPA4 mRNA level and its prognostic value were analyzed by using online database UALCAN (http://ualcan.path.uab.edu) and Kaplan-Meier plotter (www.kmplot.com), respectively. The expression of CPA4, p53 and ALDH1A1 in breast cancer and adjacent normal tissues were evaluated by IHC using the corresponding primary antibodies on a commercial tissue array (Shanghai Biochip Co., Ltd., Shanghai, China). siRNA knockdown was used to study the function of proliferation, colony formation assay and sphere formation in serum-free medium.Results: Analysis of the UALCAN datasets identified that CPA4 mRNA levels were elevated in TNBC, especially in the TP53-mutant subgroup. Furthermore, high levels of CPA4 mRNA were significantly associated with unfavourable overall survival OS in breast cancer patients. Immunohistochemistical analysis demonstrated that CPA4 levels were elevated in 32.1% of breast cancer samples (45/140), and the positive rates of ALDH1A1 and p53 in the breast cancer tissues were 25% (35/140) and 50% (70/140), respectively. Statistical analysis revealed high levels of CPA4 was significantly associated with TNBC phenotype. Correlation analysis indicated that CPA4 over-expression was positively associated with ALDH1A1 (P<0.01) and negatively correlated with p53 (P<0.05). In Kaplan-Meier survival analysis, either high CPA4 or ALDH1A1 levels was significantly correlated with poor survival in breast cancer patients. Functional studies demonstrated that down-regulation of CPA4 significantly inhibited TNBC cell proliferation, colony-formation assays in soft agar and sphere formation in serum-free medium.Conclusion: This study demonstrated for the first time that CPA4 was negatively correlates with p53 expression and inhibition of CPA4 could reduce the number of breast cancer cells with stemness property. It might be a potential target for the TNBC treatment.     

Snail在乳腺癌中的表达及其与上皮-间质转化的关系

目的研究Snail蛋白在乳腺癌组织中的表达,并探讨Snail蛋白及其调控的上皮-间质转化(EMT)与乳腺癌恶性生物学行为的相关性。方法采用免疫组织化学SP法检测20例正常乳腺组织、60例乳腺癌组织(非特殊性浸润性导管癌)及其中20例乳腺癌癌旁组织中Snail蛋白、上皮标记物E-cadherin蛋白、间质标记物Vimentin蛋白的表达;分析乳腺癌组织中3种蛋白表达强度的相关性,以及Snail蛋白表达与乳腺癌淋巴结转移的关系。结果①在正常乳腺组织、乳腺癌癌旁组织、乳腺癌组织中,Snail蛋白表达逐渐递增,其阳性率分别为0、30%、53.3%;Vimentin蛋白表达亦逐渐递增,其阳性率分别为0、40%、63.3%;E-cadherin蛋白表达则逐渐减少,其阳性率分别为100%、75%、56.7%;正常乳腺组织、乳腺癌癌旁组织与乳腺癌组织间3种蛋白的表达差异均具有统计学意义(均P0.05)。②Snail蛋白表达与Vimentin蛋白表达呈显著正相关(r=0.536、P=0.000);Snail蛋白表达与E-cadherin蛋白表达呈负相关(r=-0.413、P=0.001);3种组织中,E-cadherin和Vimentin蛋白两者的表达差异呈显著负相关(r=-0.526、P=0.000)。③Snail蛋白的表达与乳腺癌腋窝淋巴结转移呈正相关,差异有统计学意义(r=0.600、P=0.000)。结论锌指转录因子Snail可能通过参与调控EMT过程从而在乳腺癌的发生和侵袭过程中发挥重要作用,并推动乳腺癌的远处淋巴结转移。     

基于癌基因组图谱数据挖掘分析CC亚族趋化因子配体20在食管癌中的表达及临床意义

目的 探讨CC亚族趋化因子配体20(CCL20)在食管癌中的表达及对病程进展和预后的影响.方法 利用癌基因组图谱(TCGA)、UALCAN、GEO等相关数据库分析CCL20基因在食管癌组织与癌旁组织中的表达差异,通过Kaplan-Meier模型探讨CCL20表达水平与预后的关联性;分析CCL20与肥胖、甲基化等之间的关...     

Lumican and decorin are differentially expressed in human breast carcinoma

Previous studies have shown that lumican is expressed and increased in the stroma of breast tumours. Lumican expression has now been examined relative to other members of the small leucine-rich proteoglycan gene family in normal and neoplastic breast tissues, to begin to determine its role in breast tumour progression. Western blot study showed that lumican protein is highly abundant relative to decorin, while biglycan and fibromodulin are only detected occasionally in breast tissues (n=15 cases). Further analysis of lumican and decorin expression performed in matched normal and tumour tissues by in situ hybridization showed that both mRNAs were expressed by similar fibroblast-like cells adjacent to epithelium. However, lumican mRNA expression was significantly increased in tumours (n=34, p<0.0001), while decorin mRNA was decreased (p=0.0002) in neoplastic relative to adjacent normal stroma. This was accompanied by a significant increase in lumican protein (n=12, p=0.0122), but not decorin. Further evidence of altered lumican expression in breast cancer was manifested by discordance between lumican mRNA and protein localization in some regions of tumours but not in adjacent morphologically normal tissues. It is concluded that lumican is the most abundant of these proteoglycans in breast tumours and that lumican and decorin are inversely regulated in association with breast tumourigenesis.     

未绝经女性乳腺癌与血清淀粉样A1(SAA1)表达调控的关系及意义

目的 拟对乳腺癌患者外周血和组织标本进行蛋白质水平筛查分析,明确乳腺癌发生及绝经后与SAA1(血清淀粉样A1)蛋白质表达调控的关系,为建立乳腺癌早期预警及临床治疗疗效评估指标提供依据.方法 收集病理确诊的乳腺癌患者和健康志愿者外周血标本共85例,其中绝经后患者29例,未绝经患者36例,正常对照20例;手术切除的乳腺组织标本共80例,其中肿瘤组织56例,正常对照24例.选择酶联免疫吸附(ELISA)方法对外周血标本进行定量分析,明确绝经后和未绝经女性乳腺癌发生与体内SAA1血浆水平变化的关系;提取组织RNA,选择SAA1编码序列特异性PCR引物,通过定量RT-PCR分析,明确乳腺癌组织病变与细胞内SAA1转录表达调控的关系.结果 从乳腺癌患者体内血浆水平上分析,未绝经女性乳腺癌患者体内SAA1蛋白质含量明显上升,与绝经后乳腺癌患者及正常对照相比较,均有显著差异(P<0.05),但是绝经后乳腺癌与正常对照无差异(P﹥0.05);在乳腺癌组织水平上,乳腺癌发生伴有肿瘤组织内SAA1转录表达水平上升,与正常对照相比较有显著差异(P<0.05);受信者操作特性(receiver operating characteristic,ROC)曲线分析显示,采用ELISA或定量RT-PCR方法检测SAA1表达水平均有较高的灵敏度和特异性.结论 乳腺癌发生伴有体内SAA1表达调控异常,在绝经后和未绝经女性肿瘤患者有显著差异,可能与肿瘤组织内SAA1基因表达调控异常存在内在联系,此为进一步揭示乳腺癌发病机制、 早期预警和临床治疗疗效评估提供依据.     

Expression of esophageal carcinoma related gene 4 (ECRG4) and its clinical significance in prognosis of esophageal carcinoma

This study aimed to analyze the relationship between the expression level of esophageal carcinoma related gene 4 (ECRG4) in esophageal cancer tissues and the occurrence of esophageal carcinoma. 50 cases of esophageal carcinoma tissues and adjacent tissues were collected as study samples. mRNA and protein expression levels of ECRG4 in tumor tissues and adjacent tissues were analyzed by real-time fluorescence quantitative PCR, Western blot and immunohistochemistry. The relationship between the expression level of ECRG4 and the clinical and pathological features and postoperative recurrence and survival was also analyzed. Real-time fluorescent quantitative PCR and Western blot showed that the mRNA and protein levels of ECRG4 in esophageal cancer tissues were significantly down regulated (P<0.04). There was ECRG low expression in 74 cases and high expression in 17 cases. The expression level of ECRG4 protein in esophageal carcinoma tissues was closely related to tumor invasion level, TNM staging and lymph node metastasis (P<0.05), but not related to gender, age, tumor type and differentiation degree of patients (P>0.05). The cumulative recurrence rate of patients of higher ECRG expression was significantly lower than that of patients of lower ECRG4 expression in 5 years after surgery, and the cumulative recurrence rate was 5 years (P<0.05). And the cumulative survival rate of patients with high ECRG4 expression was significantly higher than that of patients with low expression of ECRG4 in 5 years after surgery (P<0.05). In conclusion, the low expression or no expression of ECRG4 in esophageal cancer tissues was closely related to the degree of tumor invasion level, TNM staging, lymph node metastasis and recurrence and survival after surgery.