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尿激酶型纤溶酶原激活物受体(uPAR)和纤溶酶原激活物抑制剂-1(PAI-1)是早期口腔鳞状细胞癌(OSCC)潜在的预测生物标志物。

Urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) are potential predictive biomarkers in early stage oral squamous cell carcinomas (OSCC).

作者信息

Magnussen Synnøve, Rikardsen Oddveig G, Hadler-Olsen Elin, Uhlin-Hansen Lars, Steigen Sonja E, Svineng Gunbjørg

机构信息

Department of Medical Biology, Faculty of Health Sciences, University of Tromsø - The Arctic University of Norway, Tromsø, Norway.

Department of Medical Biology, Faculty of Health Sciences, University of Tromsø - The Arctic University of Norway, Tromsø, Norway; Department of Otorhinolaryngology, University Hospital of North Norway, Tromsø, Norway.

出版信息

PLoS One. 2014 Jul 7;9(7):e101895. doi: 10.1371/journal.pone.0101895. eCollection 2014.

Abstract

Oral squamous cell carcinoma (OSCC) is often associated with metastatic disease and a poor 5 year survival rate. Patients diagnosed with small tumours generally have a more favourable outcome, but some of these small tumours are aggressive and lead to early death. To avoid harmful overtreatment of patients with favourable prognosis, there is a need for predictive biomarkers that can be used for treatment stratification. In this study we assessed the possibility to use components of the plasminogen activator (PA) system as prognostic markers for OSCC outcome and compared this to the commonly used biomarker Ki-67. A tissue-micro-array (TMA) based immunohistochemical analysis of primary tumour tissue obtained from a North Norwegian cohort of 115 patients diagnosed with OSCC was conducted. The expression of the biomarkers was compared with clinicopathological variables and disease specific death. The statistical analyses revealed that low expression of uPAR (p = 0.031) and PAI-1 (p = 0.021) in the tumour cells was significantly associated with low disease specific death in patients with small tumours and no lymph node metastasis (T1N0). The commonly used biomarker, Ki-67, was not associated with disease specific death in any of the groups of patients analysed. The conclusion is that uPAR and PAI-1 are potential predictive biomarkers in early stage tumours and that this warrants further studies on a larger cohort of patients.

摘要

口腔鳞状细胞癌(OSCC)常与转移性疾病及较差的5年生存率相关。被诊断为小肿瘤的患者通常预后较好,但其中一些小肿瘤具有侵袭性,会导致早期死亡。为避免对预后良好的患者进行有害的过度治疗,需要可用于治疗分层的预测性生物标志物。在本研究中,我们评估了使用纤溶酶原激活物(PA)系统的成分作为OSCC预后生物标志物的可能性,并将其与常用生物标志物Ki-67进行比较。对从挪威北部一个由115例诊断为OSCC的患者组成的队列中获取的原发性肿瘤组织进行了基于组织微阵列(TMA)的免疫组织化学分析。将生物标志物的表达与临床病理变量及疾病特异性死亡进行比较。统计分析显示,在小肿瘤且无淋巴结转移(T1N0)的患者中,肿瘤细胞中uPAR(p = 0.031)和PAI-1(p = 0.021)的低表达与低疾病特异性死亡显著相关。在分析的任何患者组中,常用生物标志物Ki-67均与疾病特异性死亡无关。结论是,uPAR和PAI-1是早期肿瘤的潜在预测性生物标志物,这值得在更大的患者队列中进行进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f6b/4084992/034110aef539/pone.0101895.g001.jpg

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