Kiss Timea, Ecsedi Szilvia, Vizkeleti Laura, Koroknai Viktoria, Emri Gabriella, Kovács Nora, Adany Roza, Balazs Margit
Department of Preventive Medicine, Faculty of Public Health, University of Debrecen, Hungary, 4028, Debrecen, Kassai str. 26/b., Hungary.
MTA-DE Public Health Research Group, University of Debrecen, Debrecen, Hungary.
Tumour Biol. 2015 Sep;36(10):7841-7. doi: 10.1007/s13277-015-3495-y. Epub 2015 May 7.
It was shown that osteopontin (OPN), a glycophosphoprotein, plays divergent roles in cancer progression. In addition to multiple intra- and extracellular functions, it facilitates migration of tumour cells, has crucial role in cell adhesion and is associated with increased metastasis formation. In previous studies, we performed global gene expression profiling on a series of primary melanoma samples and found that OPN was significantly overexpressed in ulcerated melanomas. The major purpose of this study was to define OPN expression in primary melanomas with differing biological behaviours. OPN mRNA expression was analysed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in primary melanoma tissues. Immunohistochemistry was performed using a tissue microarray. Cox regression tests were used for survival analysis. Greater than 50 % of the tissues exhibited high protein expression that was significantly associated with tumour thickness and metastasis. OPN mRNA expression was significantly increased in thicker melanomas and lesions with an ulcerated surface. Increased expression was primarily detected in advanced-stage tumours. A multivariate Cox regression analysis revealed that high OPN expression, tumour thickness and metastasis were significantly associated with reduced relapse-free survival. In summary, high OPN mRNA and protein expression were associated with a less favourable clinical outcome of primary melanoma patients. We determined that OPN is a significant predictive factor for the survival of primary melanoma patients. Based on our and others data, the high expression of OPN may have a crucial stimulatory role in tumour progression and metastasis formation, which, thus, have been proposed as potential targets for cancer diagnosis and therapy.
研究表明,骨桥蛋白(OPN)作为一种糖磷蛋白,在癌症进展中发挥着多种不同作用。除了多种细胞内和细胞外功能外,它还促进肿瘤细胞迁移,在细胞黏附中起关键作用,并与转移形成增加有关。在先前的研究中,我们对一系列原发性黑色素瘤样本进行了全基因组表达谱分析,发现OPN在溃疡型黑色素瘤中显著过表达。本研究的主要目的是确定OPN在具有不同生物学行为的原发性黑色素瘤中的表达情况。通过定量逆转录聚合酶链反应(qRT-PCR)分析原发性黑色素瘤组织中OPN mRNA的表达。使用组织芯片进行免疫组织化学分析。采用Cox回归检验进行生存分析。超过50%的组织表现出高蛋白表达,这与肿瘤厚度和转移显著相关。在较厚的黑色素瘤和有溃疡表面的病变中,OPN mRNA表达显著增加。表达增加主要在晚期肿瘤中检测到。多变量Cox回归分析显示,OPN高表达、肿瘤厚度和转移与无复发生存期缩短显著相关。总之,OPN mRNA和蛋白高表达与原发性黑色素瘤患者较差的临床结局相关。我们确定OPN是原发性黑色素瘤患者生存的一个重要预测因素。基于我们和其他研究的数据,OPN的高表达可能在肿瘤进展和转移形成中起关键的刺激作用,因此,已被提议作为癌症诊断和治疗的潜在靶点。