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uPAR、αvβ6 整联蛋白和组织因子作为口腔鳞状细胞癌分子成像靶点的潜力:免疫组织化学法评估原发肿瘤和转移灶中的九个靶点。

Potential of uPAR, αvβ6 Integrin, and Tissue Factor as Targets for Molecular Imaging of Oral Squamous Cell Carcinoma: Evaluation of Nine Targets in Primary Tumors and Metastases by Immunohistochemistry.

机构信息

Department of Otolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark.

Department of Clinical Physiology, Nuclear Medicine and PET and Cluster for Molecular Imaging, Copenhagen University Hospital-Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.

出版信息

Int J Mol Sci. 2023 Feb 14;24(4):3853. doi: 10.3390/ijms24043853.

Abstract

No clinically approved tumor-specific imaging agents for head and neck cancer are currently available. The identification of biomarkers with a high and homogenous expression in tumor tissue and minimal expression in normal tissue is essential for the development of new molecular imaging targets in head and neck cancer. We investigated the expression of nine imaging targets in both primary tumor and matched metastatic tissue of 41 patients with oral squamous cell carcinoma (OSCC) to assess their potential as targets for molecular imaging. The intensity, proportion, and homogeneity in the tumor and the reaction in neighboring non-cancerous tissue was scored. The intensity and proportion were multiplied to obtain a total immunohistochemical (IHC) score ranging from 0-12. The mean intensity in the tumor tissue and normal epithelium were compared. The expression rate was high for the urokinase-type plasminogen activator receptor (uPAR) (97%), integrin αvβ6 (97%), and tissue factor (86%) with a median total immunostaining score (interquartile range) for primary tumors of 6 (6-9), 12 (12-12), and 6 (2.5-7.5), respectively. For the uPAR and tissue factor, the mean staining intensity score was significantly higher in tumors compared to normal epithelium. The uPAR, integrin αvβ6, and tissue factor are promising imaging targets for OSCC primary tumors, lymph node metastases, and recurrences.

摘要

目前尚无临床批准的用于头颈部癌症的肿瘤特异性成像剂。鉴定在肿瘤组织中具有高且同质表达、在正常组织中表达最小的生物标志物,对头颈部癌症新的分子成像靶标的开发至关重要。我们研究了 41 例口腔鳞状细胞癌(OSCC)患者的原发肿瘤和配对转移性组织中 9 种成像靶标的表达情况,以评估它们作为分子成像靶标的潜力。对肿瘤和相邻非癌组织中的强度、比例和均匀性进行评分。将强度和比例相乘,获得总免疫组织化学(IHC)评分,范围为 0-12。比较肿瘤组织和正常上皮组织的平均强度。尿激酶型纤溶酶原激活物受体(uPAR)(97%)、整合素 αvβ6(97%)和组织因子(86%)的表达率较高,原发肿瘤的中位总免疫染色评分(四分位距)分别为 6(6-9)、12(12-12)和 6(2.5-7.5)。对于 uPAR 和组织因子,与正常上皮组织相比,肿瘤中的平均染色强度评分显著更高。uPAR、整合素 αvβ6 和组织因子是 OSCC 原发肿瘤、淋巴结转移和复发的有前途的成像靶标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fab/9962929/b2fd04e12776/ijms-24-03853-g001.jpg

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