FZD10 在骨肉瘤组织中的表达及临床意义

目的:探讨骨肉瘤组织中FZD10的表达及其临床意义。方法:用S-P免疫组织化学染色法对69例骨肉瘤及35例骨软骨瘤中FZD10蛋白的表达进行检测,并对其与骨肉瘤临床病理及预后的关系进行统计学分析。结果:FZD10在骨肉瘤和骨软骨瘤组织中阳性表达率分别为89.9%和5.7%,P<0.01。FZD10蛋白表达与Enneking分期和Price分级呈正相关,与WHO分型和预后相关。结论:骨肉瘤FZD10蛋白的表达与肿瘤恶性程度密切相关,对骨肉瘤诊断和预后评估具有重要价值。     

WNT6基因在原发性骨肉瘤组织中的表达及其临床意义

目的:骨肉瘤是最常见的恶性骨肿瘤之一,好发于青少年,致残致死率高.因此,骨肉瘤的早期诊断、治疗及其发病原因和机制已成为现阶段骨肉瘤研究领域的主要方向之一.通过观察WNT6在骨肉瘤组织中的表达,探讨其在原发性骨肉瘤发生发展中的可能作用机制,为以WNT6为指标对原发性骨肉瘤的诊断和以WNT6为靶点进行原发性骨肉瘤生物学治疗提供理论依据.方法:收集70例原发性骨肉瘤、28例骨样骨瘤和25例骨软骨瘤标本的存档蜡块,应用SP免疫组织化学染色法检测组织中WNT6蛋白的表达情况,并应用统计学处理数据分析其与骨肉瘤临床病理参数及预后的关系.结果:WNT6在原发性骨肉瘤、骨样骨瘤和骨软骨瘤组织中的阳性表达率分别为90.00 ％(63/70)、14.29 ％(4/28)和12.00 ％(3/25).骨样骨瘤组织WNT6阳性表达率与骨软骨瘤组织相比差异无统计学意义(P＞0.05);原发性骨肉瘤组织WNT6阳性表达率明显高于骨样骨瘤组织和骨软骨瘤组织,差异均有统计学意义(均P＜0.05).WNT6在骨肉瘤组织中的表达与Enneking分期、肺转移和预后呈正相关关系.结论:WNT6在原发性骨肉瘤中的表达明显上调,WNT6表达与骨肉瘤的Enneking分期、年龄、肺转移等相关,同时WNT6高表达患者生存率降低,对骨肉瘤的诊断和预后评估具有重要价值,并在临床可能成为一个诊断原发性骨肉瘤的检测指标,为骨肉瘤的生物学治疗提供新的靶点.     

Sox2在骨肉瘤组织中的表达及其临床病理意义

目的研究Sox2在临床骨肉瘤标本中表达,并探讨其表达与肿瘤的生物学特征及临床预后的关系。方法采用免疫组织化学Maxvision检测Sox2蛋白在54例人骨肉瘤标本的表达,12例骨化性肌炎作为正常对照。结果骨肉瘤标本中Sox2阳性表达率为20.69%(12/58),而在骨化性肌炎中Sox2阳性表达率为0%(0/12),Sox2在骨肉瘤标本中的阳性率显著高于对照组骨化性肌炎(P0.01)。Sox2的表达与骨肉瘤临床Enneking分期有关(P0.05),与患者的年龄、性别、部位、组织学类型等其它临床病理因素无关(P0.05)。结论 Sox2可能在骨肉瘤的发生、发展和转移中发挥重要作用,提示Sox2的表达可考虑作为骨肉瘤临床评价生物学行为及判断预后的指标之一。     

Wnt5a、Ror2在骨肉瘤中的表达及临床意义

目的:探讨骨肉瘤组织中Wnt5a、Ror2表达。方法:免疫组织化学法检测Wnt5a、Ror2在实验组55例骨肉瘤和对照组15例骨软骨瘤组织标本中的表达。结果:Wnt5a、Ror2在骨肉瘤组的表达均明显高于骨软骨瘤组(Wnt5a:74.55%、20.00%,Ror2:13.33%、70.91%,P0.05)。Wnt5a、Ror2在骨肉瘤出现转移的表达明显高于未转移(Wnt5a:100%、66.67%,Ror2:100%、61.90%,P0.05),在骨肉瘤Enneking分期中,Wnt5aⅠ期11.11%,Ⅱ期84.38%,Ⅲ期100.00%,Ror2Ⅰ期22.22%,Ⅱ期72.73%,Ⅲ期100.00%,Ⅰ期与Ⅱ期间和Ⅰ期与Ⅲ期间差异皆有统计学意义(P0.05),而Ⅱ期与Ⅲ期间差异皆无统计学意义(P0.05),Wnt5a、Ror2两者之间的表达呈正相关分布(骨肉瘤组:r=0.844,P0.01;骨软骨瘤组:r=0.808,P0.01),但在骨肉瘤患者性别、年龄以及骨肉瘤病理分型组中表达无明显差异(P0.05)。结论:Wnt5a、Ror2在骨肉瘤中存在高度表达,可能具有促癌作用,并与其恶性程度和侵袭转移有关,二者协同作用。     

Nucleostemin和PUMA在骨肉瘤细胞的表达及意义

目的研究Nucleostemin(NS)和p53上调凋亡调控因子(P53 up-regulated modulator of apoptosis,PUMA)在骨肉瘤中的表达。探讨其表达与骨肉瘤的病理分型,临床外科分期的关系。方法收集30例骨肉瘤患者手术标本,采用免疫组织化学SABC法检测这组标本中NS和PUMA的表达,应用图像分析系统测量其阳性表达的平均光密度值。结果 1.NS蛋白定位于细胞核,NS在骨肉瘤组表达高于骨软骨瘤组(P<0.05),在骨肉瘤组随Ennking分期的递增而增加(P<0.05),NS的表达与骨肉瘤的病理分型无关(P>0.05)。2.PUMA定位于细胞质,在骨肉瘤组表达明显低于骨软骨瘤组(P<0.05),其表达与骨肉瘤Ennking分期和病理分型无关(P>0.05)。结论 NS和PUMA在骨肉瘤发生和发展过程中起着重要的作用。     

PTEN和Fas在骨肉瘤中的表达及其临床意义

目的探讨PTEN和Fas的表达在骨肉瘤发生中的可能作用及其临床意义.方法用SP免疫组化方法检测PTEN和Fas在38例骨肉瘤及20例骨软骨瘤中的表达.结果 PTEN在骨肉瘤中表达阳性率为55.3%,在骨软骨瘤中为90.0%,二者相比差异有非常显著意义(P<0.01).Fas在骨肉瘤中表达阳性率为73.7%,在骨软骨瘤中为95.0%,二者相比差异有显著意义(P<0.05).骨肉瘤中PTEN和Fas的表达呈显著正相关(r=0.39,P<0.01).PTEN的低表达与分化程度无关,与肺转移有关,Fas的低表达与分化程度及肺转移有关.结论 PTEN和Fas与骨肉瘤的发生有关,且呈正相关,联合检测PTEN和Fas的表达将对骨肉瘤的早期诊断,判定恶性程度及预后具有指导意义.     

AKT和PTEN在骨肉瘤中表达的相关研究

目的探讨骨肉瘤中AKT和PTEN表达的意义及其临床价值。方法采用免疫组织化学SABC法检测48例骨肉瘤、15例骨软骨瘤标本中AKT、PTEN表达的阳性细胞。结果AKT的阳性表达率在骨肉瘤中为87.5%,在骨软骨瘤中为33.3%,两者比较有显著差异(P<0.05);PTEN的阳性表达率在骨肉瘤中为41.7%,在骨软骨瘤中为86.7%,两者差异显著(P<0.01);在骨肉瘤中,AKT与PTEN呈负相关(r=-0.453,P<0.05)。AKT蛋白表达在有肿瘤复发、肺转移的骨肉瘤中的表达高于无复发及无肺转移的骨肉瘤(P<0.05),而PTEN则相反(P<0.05)。两者的表达均与年龄、性别、肿瘤的大小无关(P>0.05)。结论AKT蛋白的表达在骨肉瘤发生发展中起重要作用,PTEN则可抑制这一作用过程。     

VEGF和PCNA在骨肉瘤组织中的表达及其临床意义

目的:探讨血管内皮生长因子(VEGF)和增殖细胞核抗原(PCNA)在骨肉瘤组织中的表达及其与微血管密度(MVD)、预后的关系。方法:用免疫组织化学法检测64例骨肉瘤组织中VEGF、PCNA的表达和MVD。结果:VEGF阳性表达主要在胞浆,PCNA的阳性表达主要在胞核。VEGF、PCNA表达与MVD存在显著关联(P<0.05),与骨肉瘤转移和5年生存率有显著关联性(P<0.05)。VEGF表达与PCNA表达密切相关(P<0.05)。结论:VEGF和PCNA指标可作为判断骨肉瘤预后的重要指标。     

ULBP2在胰腺癌组织中的表达及临床意义

目的:探讨ULBP2在胰腺癌组织中的表达及其与胰腺癌发生发展的相关性.方法:应用免疫组化检测ULBP2在胰腺癌中的表达,分析ULBP2与胰腺癌临床病理学特征的相关性.结果:ULBP2在胰腺癌组织中的阳性表达率为87.5％ (35/40),正常胰腺组织阳性表达率为18.1％ (2/11),癌组织与正常胰腺组差异显著(x2=21.865,P＜0.01).ULBP2在胰腺癌组织中的表达水平与肿瘤远处转移和分化程度密切相关(x2=4.322,6.400 P=0.038,0.041).结论:ULBP2可能在胰腺癌发生发展中起重要作用,ULBP2有望成为胰腺癌免疫治疗的靶点.     

MRP在胰腺癌组织中的表达及其临床意义

目的：了解MRP蛋白在胰腺癌组织中的表达情况,并探讨其临床意义。方法：应用免疫组织化学法检测72例胰腺癌组织,10例正常胰腺组织中MRP蛋白的表达,并分析其与临床病理学特征及预后的关系。结果：MRP蛋白在胰腺癌组织中的阳性表达率为91．7％,明显高于其在正常胰腺组织中的表达（p〈0．05）。胰腺癌组织中的MRP蛋白高表达与病理学分级低显著相关（p=0．031）,亦与年龄有关（p〈0．05）,而与肿瘤生长部位、肿瘤大小、淋巴结有无转移、临床分期及神经有无浸润无显著相关性（p〉0．05）。MRP蛋白高表达者的中位生存期明显长于低表达者（21．7个月vs11．1个月,p=0．040）。结论：胰腺癌组织中MRP蛋白的高表达与胰腺癌术后的预后好相关,检测胰腺癌中MRP蛋白的表达具有重要的临床意义。     

Expression and clinical significance of galectin-3 in osteosarcoma

Galectin-3 is a multifunctional β-galactoside-binding protein which has been shown to play a role in carcinogenesis. However, the involvement of galectin-3 in osteosarcoma remains unclear. In this study, we aimed to examine the serum level of galectin-3 in osteosarcoma patients and healthy controls, and the protein expression of galectin-3 in osteosarcoma tissues and their adjacent non-malignant tissues. We further aimed to investigate the clinical significance of galectin-3 serum and protein expression levels. Galectin-3 serum level was evaluated using ELISA in 132 osteosarcoma patients and 184 healthy controls, while the protein expression of galectin-3 was determined using immunohistochemistry in the malignant and the surrounding non-malignant tissues of the same 132 osteosarcoma patients. Our results showed that the mean galectin-3 serum level was significantly higher in patients than in controls (2.35 ± 0.91 ng/ml vs. 0.86 ± 0.20 ng/ml) (p < 0.0001). Among patients, a higher galectin-3 serum level was significantly associated with the Enneking stage of cancer (p < 0.0001). In addition, we found a significant overrepresentation of high galectin-3 expression in osteosarcoma tissues than in non-malignant tissues (p < 0.0001). Galectin-3 expression in osteosarcoma tissues was also found to be correlated with the Enneking stage of cancer (p < 0.0001) and the occurrence of metastasis (p < 0.0001). In conclusion, galectin-3 could serve as a useful prognostic marker in osteosarcoma.     

Oncogenic gene TRIM10 confers resistance to cisplatin in osteosarcoma cells and activates the NF-κB signaling pathway

Deregulation of tripartite motif (TRIM) family proteins contribute to multiple biological processes such as neurodegeneration, development, inflammation, cell survival, apoptosis, and carcinogenesis. However, the biological function and molecular mechanism of TRIM family proteins in osteosarcoma chemoresistance remain unclear. In the current study, we found the protein expression of TRIM10 was markedly overexpressed in cisplatin resistance's osteosarcoma tissues and TRIM10 overexpression was inversely correlated with osteosarcoma patient survival. Furthermore, overexpression of TRIM10 confers cisplatin resistance on osteosarcoma cells; however, repressing TRIM10 sensitized osteosarcoma cell lines to cisplatin cytotoxicity in vitro. Mechanically, TRIM10 upregulated the nuclear levels of p65, thereby activating canonical NF-κB signaling. Taken together, our results suggest that TRIM10 contributed to cisplatin resistance in osteosarcoma cells, and targeting the TRIM10/p65 axis may represent a promising strategy to enhance cisplatin response in osteosarcoma patients with chemoresistance.     

CyclinE和p27蛋白在骨肉瘤中的表达及临床意义

目的探讨CyclinE和p27在骨肉瘤中表达及临床意义。方法检测108例骨肉瘤石蜡包埋组织中CyclinE和p27蛋白表达水平,统计分析其与患者临床病理因素和预后之间的关系。结果骨肉瘤组织中CyclinE的阳性率为68．52％,p27的阳性率为26．85％;CyclinE和p27蛋白表达水平与骨肉瘤病理分级、软组织浸润、远处转移、Enneking分期及患者整体生存期有关（P〈0．05）;CyclinE蛋白阳性组骨肉瘤患者5年存活率显著低于阴性组;而p27蛋白阳性组患者5年存活率显著高于阴性组（P〈0．05）。Cox多因素分析提示软组织浸润及远处转移状态、病理分级、Enneking外科分期、CyclinE和p27蛋白表达水平是影响骨肉瘤患者预后的独立危险因素（P〈0．05）。结论CyclinE和p27蛋白表达水平是判断骨肉瘤患者预后的新指标,联合检测CyclinE和p27蛋白表达水平对骨肉瘤的进展、预后判断有重要意义。     

CXCL10和MMP-13在妊娠滋养细胞疾病滋养细胞中的表达及其临床意义

目的检测妊娠滋养细胞疾病滋养细胞中CXCL10和MMP-13表达情况,探讨其在滋养细胞疾病浸润和转移中的作用。方法采用免疫组织化学Powervision法检测40例早孕绒毛,30例葡萄胎,18例葡萄胎恶变(随访发生恶变),35例滋养细胞肿瘤(28例绒癌,7例胎盘部位滋养细胞肿瘤)中CXCL10和MMP-13的表达。结果CXCL10和MMP-13在滋养细胞肿瘤中表达阳性率和免疫反应性强度最高;在葡萄胎恶变组中表达阳性率和免疫反应性强度较高,但是低于在滋养细胞肿瘤中的表达阳性率和免疫反应性强度;在葡萄胎组和早孕绒毛组中表达阳性率和免疫强度较低。CXCL10和MMP-13在滋养细胞肿瘤中的表达,年龄<40岁组中表达低于年龄>40岁组;在临床分期分组(Ⅰ、Ⅱ)中表达低于临床分期分组(Ⅲ、Ⅳ);在FIGO预后评分分组低危组中表达低于高危组。结论CXCL10和MMP-13在早孕绒毛组织中低表达,而在滋养细胞肿瘤中高表达,提示其可能参与滋养细胞疾病的浸润和转移过程,因此联合检测CXCL10和MMP-13的表达可能对葡萄胎恶变的早期诊断以及对滋养细胞肿瘤的预后评估提供依据。     

Proteomics of osteosarcoma

Osteosarcoma (OS) is the most common primary malignant tumor of bone and the third most common cancer in childhood and adolescence. Nowadays, early diagnosis, drug resistance and recurrence of the disease represent the major challenges in OS treatment. Post-genomics, and in particular proteomic technologies, offer an invaluable opportunity to address the level of biological complexity expressed by OS. Although the main goal of OS oncoproteomics is focused on diagnostic and prognostic biomarker discovery, in this review we describe and discuss global protein profiling approaches to other aspects of OS biology and pathophysiology, or to investigate the mechanism of action of chemotherapeutics. In addition, we present proteomic analyses carried out on OS cell lines as in vitro models for studying osteoblastic cell biology and the attractive opportunity offered by proteomics of OS cancer stem cells.     

Expression profiling of long noncoding RNAs associated with vasculogenic mimicry in osteosarcoma

Osteosarcoma (OS) is the most common highly malignant bone tumor in teens. Vasculogenic mimicry (VM) is defined as de novo extracellular matrix-rich vascular-like networks formed by highly aggressive tumor cells. We previously reported the presence of VM and it is an unfavorable prognostic factor in OS patients. Long noncoding RNAs (lncRNAs) are aberrantly expressed in OS and involved in cancer cell VM. However, lncRNAs in VM formation of OS have not been investigated. We, therefore, profiled the expression of lncRNAs in highly aggressive OS cell line 143B compared with its parental poorly aggressive cell line HOS. The differentially expressed (DE) lncRNAs and messenger RNA (mRNAs) were subjected to constructed lncRNA-mRNA coexpressed network. The top-ranked hub gene lncRNA n340532 knockdown 143B cells were used for in vitro and in vivo VM assays. The annotation of DE lncRNAs was performed according to the coexpressed mRNAs by Gene Ontology and pathway analysis. A total of 1360 DE lncRNAs and 1353 DE mRNAs were screened out. lncRNA MALAT1 and FTX, which have known functions related to VM formation and tumorigenesis were identified in our data. The coexpression network composed of 226 lncRNAs and 118 mRNAs in which lncRNA n340532 had the highest degree number. lncRNA n340532 knockdown reduced VM formation in vitro. The suppression of n340532 also exhibited potent anti-VM and antimetastasis effect in vivo, suggesting its potential role in OS VM and metastasis. Furthermore, n340532 coexpressed with 10 upregulation mRNAs and 3 downregulation mRNAs. The enriched transforming growth factor-β signaling pathway, angiogenesis and so forth were targeted by those coexpressed mRNAs, implying n340532 may facilitate VM formation in OS through these pathways and gene functions. Our findings provide evidence for the potential role of lncRNAs in VM formation of OS that could be used in the clinic for anti-VM therapy in OS.