基质金属蛋白酶-9在胆管癌中的表达与侵袭转移的关系

目的探讨MMP-9在胆管癌中的表达及意义.方法应用免疫组化学(SP法)检测55例胆管癌MMP-9表达情况.结果在胆管癌中加MMP-9阳性表达显著高于正常胆管组织.在胆管乳头状腺癌、管状腺癌、粘液腺癌和腺鳞癌中,MMP-9阳性表达与组织类型无关.MMP-9阳性表达与组织分化和临床分期显著相关.在有淋巴结转移组,MMP-9阳性表达显著高于淋巴结未转移组.结论MMP-9阳性表达与胆管癌侵袭转移关系密切,MMP-9检测将有助于评估肿瘤侵袭转移潜能.     

MMP-9在上皮性卵巢癌组织中的表达及临床意义

目的 探讨MMP-9在上皮性卵巢癌组织中的表达及临床意义.方法 采用免疫组化方法检测15例正常卵巢组织、15例良性上皮性卵巢肿瘤组织和89例上皮性卵巢癌组织中MMP-9蛋白的表达.结果 正常卵巢组织及良性卵巢肿瘤组织中,MMP-9蛋白不表达或低表达.上皮性卵巢癌中,MMP-9表达水平明显升高,高表达率为56.18%.MMP-9高表达与肿瘤晚期、瘤细胞的低分化、肿瘤转移有显著的相关性(P均＜0.05).结论 上皮性卵巢癌组织中,MMP-9蛋白表达上调.MMP-9蛋白在上皮性卵巢癌的生长和转移过程中发挥着重要的作用,可能作为判断卵巢癌预后的指标.     

食管鳞癌中基质金属蛋白酶-9的表达及意义

目的研究基质金属蛋白酶-9(MMP-9)在食管鳞癌中的表达情况及其与肿瘤浸润和淋巴结转移的关系.方法用免疫组织化学法检测75例食管鳞癌组织及其相应正常粘膜中MMP-9的表达.结果食管鳞癌组织MMP-9基因表达高于正常食道组织,MMP-9的表达与食管鳞癌浸润深度和淋巴结转移呈正相关.结论在食管鳞癌中MMP-9的表达与肿瘤的发展有关,可能成为食管鳞癌恶性生物学行为的指标.     

三阴性乳腺癌中MMP-9的表达及意义

目的:探讨三阴性乳腺癌(TNBC)中基质金属蛋白酶-9(MMP-9)的表达及意义.方法:收集2012年1月至2013年12月乳腺浸润性导管癌共158例,应用免疫组织化学及荧光原位杂交技术将乳腺癌分为65例TNBC、93例非TNBC.免疫组织化学检测MMP-9的表达情况,明确MMP-9在二组间表达的区别.分析MMP-9在TNBC中与临床病理特征关系,并随访65例TNBC患者3年复发或转移率,探讨MMP-9表达与3年复发转移率间的关系.结果:TNBC中MMP-9表达明显高于非TNBC(P<0.05);TNBC中MMP-9表达与年龄和肿瘤大小无关(P>0.05),与TNM分期、组织学分级、淋巴结状态及脉管浸润有关,差异具有统计学意义(P<0.05);MMP-9阳性的TNBC患者3年复发转移率高达76.09%,明显高于MMP-9阴性组47.37%,差异具有统计学意义(P<0.05).结论:TNBC中MMP-9表达明显高于非TNBC,MMP-9与TNBC浸润转移有关,对预测3年复发转移有明显意义.     

口腔鳞癌中MMP-9的表达与巨噬细胞测定的意义

目的：探讨基质金属蛋白酶9（Matrix metalloproteinase 9,MMP-9）的表达和巨噬细胞的浸润在口腔鳞癌的侵袭和转移中的意义及相互关系.方法：采用免疫组化SABC法分别检测MMP-9和CD68（标记巨噬细胞）在42例口腔鳞癌和10例口腔正常组织的表达情况.结果：MMP-9的表达和巨噬细胞计数在口腔鳞癌中均显著高于正常组（P＜0.05）;肿瘤组织中MMP-9的表达及巨噬细胞计数与口腔鳞癌的淋巴结转移、TNM分期有关（P＜0.05）;而且它们之间呈正相关关系（γ=0.443,P＜0.01）.结论：MMP-9和巨噬细胞可能在口腔鳞癌的侵袭及转移中发挥重要作用,其机制可能与巨噬细胞作用于肿瘤细胞并协助上调肿瘤细胞中MMP-9的表达有关.     

子宫颈鳞癌组织中基质金属蛋白酶MMP-2和MMP-9的表达及其意义

目的探讨基质金属蛋白酶MMP-2和MMP-9与宫颈鳞癌的发生、发展及转移的关系.方法免疫组化S-P法测定MMP-2和MMP-9表达及分布;明胶酶谱法测定活性型MMP-2及MMP-9蛋白的含量;RT-PCR技术检测MMP-2及MMP-9 mRNA表达水平.结果宫颈癌组织中MMP-2及MMP-9的阳性表达率为77.78%和66.67%,明显高于在CIN(10%及20%)及正常宫颈组织中表达率.淋巴转移组MMP-2及MMP-9的阳性率均显著高于非淋巴转移组,P<0.05.在宫颈鳞癌组织中MMP-2及MMP-9酶活性显著高于CIN及正常宫颈组织,P<0.01.MMP-2及MMP-9 mRNA在宫颈鳞癌中的表达量亦显著高于在CIN及正常宫颈组织的表达量,P<0.01.结论MMP-2及MMP-9与宫颈鳞癌的发生、发展及转移有关,MMP-2及MMP-9的增高可作为判断宫颈鳞癌具有转移倾向的临床参考指标.     

累及中枢神经系统多发性骨髓瘤9例

目的:探讨多发性骨髓瘤累及中枢神经系统的诊治及其预后.方法:回顾性分析9例累及中枢神经系统的多发性骨髓瘤患者的诊治及其预后.结果:418例多发性骨髓瘤患者中有9例并发中枢神经系统侵犯,发生率为2.2%,其中脑膜受累最为常见(5/9),其次为垂体(2/9).所有患者在诊治过程中均伴有多处其他部位软组织的髓外病变.中位随访时间为30个月,9例患者的中位生存时间为29个月,累及中枢神经系统后中位生存时间仅为5个月.结论:多发性骨髓瘤累及中枢神经系统较为少见,受累部位以脑膜最为常见,常合并其他部位的软组织浆细胞瘤.累及中枢神经系统的多发性骨髓瘤患者预后不良,在治疗上尚缺乏有效的干预手段.     

VEGF、VEGFR-1和MMP-9对良恶性胸腔积液的诊断价值

目的 探讨血管肉皮生长因子(VEGF)、受体VEGFR-1和基质金属蛋白酶-9(MMP-9)表达在良、恶性胸腔积液鉴别诊断中的价值.方法 采用ELISA法,检测35例恶性胸腔积液、33例良性胸腔积液患者胸腔积液中VEGF,VEGFR-1和MMP-9表达水平,并进行相关性比较分析.结果 恶性胸腔积液组中VEGF、VEGFR-1表达均明显高于良性胸腔积液,MMP-9表达明显低于良性胸腔积液,差异均有统计学意义(P＜0.05).恶性胸腔积液中VEGF,VEGFR-1和MMP-9表达水平呈正相关.VEGF,VEGFR-1和MMP-9与恶性胸腔积液的病理类型无相关性.结论 胸腔积液中VEGF,VEGFR-1和MMP-9表达可以作为良性和恶性胸腔积液鉴别诊断的标志物.     

基质金属蛋白酶-9 mRNA和蛋白在食管癌组织中的表达及其临床意义

目的　探讨基质金属蛋白酶 9(MMP 9)mRNA及蛋白在食管癌组织中的表达。方法　采用半定量RT PCR法及免疫组织化学方法 ,分别检测 40例食管癌及癌旁 2cm与癌旁≥ 5cm组织中MMP 9mRNA及蛋白的表达。结果　食管癌、癌旁 2cm和癌旁≥ 5cm组织中 ,MMP 9蛋白阳性率分别为 72 .5 % ( 2 9/4 0 )、5 2 .5 % ( 2 1/4 0 )和 3 0 .0 % ( 12 /4 0 ) ,MMP 9mRNA阳性率分别为 77.5 % ( 3 1/4 0 )、60 .0 % ( 2 4/4 0 )和 3 7.5 % ( 15 /4 0 ) ,癌组织与癌旁≥ 5cm组织比较 ,有显著性差异 ( χ2 =14 .45 9,P <0 .0 5 )。癌组织中MMP 9mRNA表达水平显著高于癌旁 2cm及癌旁≥ 5cm组织 (P <0 .0 5 )。癌组织中MMP 9mRNA表达水平与临床分期、组织分化程度及淋巴结转移状态密切相关 (相关系数为 0 .8862、0 .7495和 0 .890 7,P <0 .0 5 )。结论　MMP 9在食管癌侵袭及转移过程中发挥重要作用 ,可作为判断其预后的指标之一     

基质金属蛋白酶9和14在子宫内膜异位症中的表达

 目的　明确MMP 9和MMP 14在子宫内膜异位症中的表达。方法　利用原位杂交法检测MMP 9和MMP 14在正常子宫内膜和子宫内膜异位症病灶中的表达情况。结果　 (1)MMP 14在正常内膜中无表达 ,在异位病灶中阳性表达率为 2 0 .0 % (P <0 .0 5 ) ;(2 )MMP 9在正常内膜中仅表达于增殖期内膜 ,阳性表达率为 6 .9% ,在异位病灶中阳性表达率为 4 3.3% (P <0 .0 1)。结论　 (1)在子宫内膜异位病灶中MMP 14表达率低而MMP 9则高表达 ;(2 )MMP 14和MMP 9与内膜异位症的发生有密切关系 ,但二者间无相关性。     

SPAG9 is overexpressed in human astrocytoma and promotes cell proliferation and invasion

Sperm-associated antigen 9 (SPAG9) is a recently characterized oncoprotein involved in the progression of several human malignancies. The present study aims to investigate the expression pattern and biological roles of SPAG9 protein in human astrocytoma. SPAG9 expression was analyzed in 105 astrocytoma specimens by immunohistochemistry. We observed negative staining in normal astrocytes and positive staining of SPAG9 in 63 out of 105 (60 %) astrocytoma samples. Overexpression of SPAG9 correlated with tumor grade (p?<?0.001). Small interfering RNA knockdown was performed in U251 and U87 cell lines with relatively high SPAG9 expression. Using methylthiazolyldiphenyl-tetrazolium bromide assay and Matrigel invasion assay, we were able to show that SPAG9 depletion in astrocytoma cell lines inhibited cell proliferation and invasion in both cell lines. In addition, mRNA and protein levels of matrix metallopeptidase 9 (MMP9) were downregulated, while the levels of tissue inhibitor of metalloproteinase 1 (TIMP1) and TIMP2 were not changed, indicating that SPAG9 might regulate invasion through MMP9. In conclusion, SPAG9 serves as an important oncoprotein in human astrocytoma by regulating cell proliferation and invasion.     

SPAG9 is overexpressed in human prostate cancer and promotes cancer cell proliferation

Sperm-associated antigen 9 (SPAG9) was recently reported to be overexpressed in several cancers and associated with the malignant behavior of cancer cells. However, the expression pattern of SPAG9 and its clinical significance in human prostate cancer have not been reported. In the present study, we analyzed SPAG9 expression in human prostate cancer tissues by immunohistochemistry and found that SPAG9 was overexpressed in 36.5 % of prostate cancer specimens. There was a significant association between SPAG9 overexpression and tumor stage (p?=?0.0020) and Gleason score (p?=?0.0377). Transfection of SPAG9 plasmid was performed in PC-3 cell line and siRNA knockdown was carried out in DU145 cells. Colony formation and MTT showed that SPAG9 overexpression promoted while siRNA knockdown inhibited prostate cancer cell proliferation. In addition, we found that SPAG9 could regulate cyclin D1 and cyclin E protein expression. In conclusion, SPAG9 is overexpressed in human prostate cancers and contributes to prostate cancer cell growth, possibly through cyclin protein regulation.     

精子相关抗原9在膀胱移行细胞癌中的表达及临床意义

目的： 探讨精子相关抗原9 (sperm-associated antigen 9,SPAG9)在膀胱移行细胞癌 (bladder transitional cell carcinoma, BTCC)中的表达并分析其临床意义。方法：选取经临床病理诊断的BTCC标本98例,正常膀胱组织30例,应用免疫组化染色方法检测SPAG9在BTCC中的表达和分布情况,分析其与肿瘤的临床分期、病理分级及2年复发率的关系。结果：SPAG9在正常膀胱组织中为阴性表达,而在BTCC组中的阳性表达率为75.5% (74/98),并且随着肿瘤分期和分级的升高SPAG9蛋白的表达增加,SPAG9阳性表达率在病理分级G1、G2与G3级之间的差异有统计学意义 (P<0.05);在临床分期Ta与T1组间的差异有统计学意义 (P<0.05); SPAG9蛋白表达阳性的非肌层浸润性膀胱癌患者,其2年复发率显著高于阴性表达者 (P<0.05)。结论：SPAG9蛋白在BTCC中呈高表达状态,可成为BTCC有意义的肿瘤标志物,并有可能作为判断 BTCC侵袭力、监测复发的重要指标。阻断SPAG9表达有望成为膀胱癌靶向治疗的新靶点。     

Overexpression of SPAG9 correlates with poor prognosis and tumor progression in hepatocellular carcinoma

Sperm-associated antigen 9 (SPAG9) was reported as a novel biomarker for several cancers and associated with the malignant behavior of cancer cells. However, its expression pattern and biological role in human hepatocellular carcinoma (HCC) have not been reported. In the present study, we analyzed SPAG9 expression in human HCC tissues by immunohistochemistry and found that SPAG9 overexpression is correlated with tumor stage (p?p?=?0.019), tumor size (p?=?0.034), AFP levels (p?=?0.006), and tumor relapse (p?=?0.0017). Furthermore, SPAG9 overexpression is correlated with poor overall survival (p?p?=?0.002). Transfection of SPAG9 small interfering RNA (siRNA) was performed in Bel-7402 cell line. Colony formation and MTT showed that SPAG9 siRNA knockdown inhibited HCC cell proliferation. We also found that SPAG9 depletion could increase cell apoptosis. In addition, the level of cyclin D1 and cyclin E protein expression was downregulated after siRNA treatment. In conclusion, SPAG9 is overexpressed in human HCC and serves as a prognostic marker. SPAG9 contributes to cancer cell growth through regulation of cyclin proteins.     

Sperm-associated antigen 9 (SPAG9) promotes the survival and tumor growth of triple-negative breast cancer cells

Recently, we demonstrated the association of sperm-associated antigen 9 (SPAG9) expression with breast cancer. Among breast cancer, 15 % of the cancers are diagnosed as triple-negative breast cancers (TNBC) based on hormone receptor status and represent an important clinical challenge because of lack of effective available targeted therapy. Therefore, in the present investigation, plasmid-based small hairpin (small hairpin RNA (shRNA)) approach was used to ablate SPAG9 in aggressive breast cancer cell line model (MDA-MB-231) in order to understand the role of SPAG9 at molecular level in apoptosis, cell cycle, and epithelial-to-mesenchymal transition (EMT) signaling. Our data in MDA-MB-231 cells showed that ablation of SPAG9 resulted in membrane blebbing, increased mitochondrial membrane potential, DNA fragmentation, phosphatidyl serine surface expression, and caspase activation. SPAG9 depletion also resulted in cell cycle arrest in G0–G1 phase and induced cellular senescence. In addition, in in vitro and in vivo xenograft studies, ablation of SPAG9 resulted in upregulation of p21 along with pro-apoptotic molecules such as BAK, BAX, BIM, BID, NOXA, AIF, Cyto-C, PARP1, APAF1, Caspase 3, and Caspase 9 and epithelial marker, E-cadherin. Also, SPAG9-depleted cells showed downregulation of cyclin B1, cyclin D1, cyclin E, CDK1, CDK4, CDK6, BCL2, Bcl-xL, XIAP, cIAP2, MCL1, GRP78, SLUG, SNAIL, TWIST, vimentin, N-cadherin, MMP2, MMP3, MMP9, SMA, and β-catenin. Collectively, our data suggests that SPAG9 promotes tumor growth by inhibiting apoptosis, altering cell cycle, and enhancing EMT signaling in in vitro cells and in vivo mouse model. Hence, SPAG9 may be a potential novel target for therapeutic use in TNBC treatment.