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尿激酶型纤溶酶原激活物受体(uPAR)、组织因子(TF)和表皮生长因子受体(EGFR)在口咽鳞状细胞癌中的表达模式及其作为分子成像靶点的潜力。

Expression patterns of uPAR, TF and EGFR and their potential as targets for molecular imaging in oropharyngeal squamous cell carcinoma.

作者信息

Christensen Anders, Grønhøj Christian, Jensen Jakob Schmidt, Lelkaitis Giedrius, Kiss Katalin, Juhl Karina, Charabi Birgitte Wittenborg, Mortensen Jann, Kjær Andreas, Von Buchwald Christian

机构信息

Department of Otolaryngology, Head & Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, DK‑2100 Copenhagen, Denmark.

Department of Pathology, Rigshospitalet, University of Copenhagen, DK‑2100 Copenhagen, Denmark.

出版信息

Oncol Rep. 2022 Aug;48(2). doi: 10.3892/or.2022.8359. Epub 2022 Jul 1.

Abstract

The clinical introduction of molecular imaging for the management of oropharyngeal squamous cell carcinoma (OPSCC) relies on the identification of relevant cancer‑specific biomarkers. The application of three membrane‑bound receptors, namely urokinase‑type plasminogen activator receptor (uPAR), tissue factor (TF) and EGFR have been previously explored for targeted imaging and therapeutic strategies in a broad range of solid cancers. The present study aimed to investigate the expression patterns of uPAR, EGFR and TF by immunohistochemistry (IHC) to evaluate their potential for targeted imaging and prognostic value in OPSCC. In a retrospective cohort of 93 patients with primary OPSCC, who were balanced into the 45 human papillomavirus (HPV)‑positive and 48 HPV‑negative groups, the IHC‑determined expression profiles of uPAR, TF and EGFR in large biopsy or tumor resection specimens were analyzed. Using the follow‑up data, overall survival (OS) and recurrence‑free survival were measured. Specifically, associations between survival outcome, biomarker expression and clinicopathological factors were examined using Cox proportional hazards model and log‑rank test following Kaplan‑Meier statistics. After comparing the expression pattern of biomarkers within the tumor compartment with that in the adjacent normal tissues, uPAR and TF exhibited a highly tumor‑specific expression pattern, whereas EGFR showed a homogeneous expression within the tumor compartment as well as a consistent expression in the normal mucosal epithelium and salivary gland tissues. The positive expression rate of uPAR, TF and EGFR in the tumors was 98.9, 76.3 and 98.9%, respectively. No statistically significant association between biomarker expression and survival outcome could be detected. Higher uPAR expression levels had a trend towards reduced OS according to results from univariate analysis (P=0.07; hazard ratio=2.01; 95% CI=0.92‑4.37). Taken together, these results suggest that uPAR, TF and EGFR may be suitable targets for molecular imaging and therapy in OPSCC. In particular, uPAR may be an attractive target owing to their high positive expression rates in tumors and a highly tumor‑specific expression pattern.

摘要

分子成像技术在口咽鳞状细胞癌(OPSCC)管理中的临床应用依赖于相关癌症特异性生物标志物的识别。三种膜结合受体,即尿激酶型纤溶酶原激活物受体(uPAR)、组织因子(TF)和表皮生长因子受体(EGFR)的应用,先前已在多种实体癌的靶向成像和治疗策略中进行了探索。本研究旨在通过免疫组织化学(IHC)研究uPAR、EGFR和TF的表达模式,以评估它们在OPSCC中的靶向成像潜力和预后价值。在一个由93例原发性OPSCC患者组成的回顾性队列中,这些患者被均衡地分为45例人乳头瘤病毒(HPV)阳性组和48例HPV阴性组,分析了在大活检或肿瘤切除标本中通过IHC确定的uPAR、TF和EGFR的表达谱。利用随访数据,测量总生存期(OS)和无复发生存期。具体而言,在Kaplan-Meier统计之后,使用Cox比例风险模型和对数秩检验来检查生存结果、生物标志物表达与临床病理因素之间的关联。在将肿瘤区域内生物标志物的表达模式与相邻正常组织中的表达模式进行比较后,uPAR和TF表现出高度肿瘤特异性的表达模式,而EGFR在肿瘤区域内表现出均匀表达,并且在正常黏膜上皮和唾液腺组织中表达一致。肿瘤中uPAR、TF和EGFR的阳性表达率分别为98.9%、76.3%和98.9%。未检测到生物标志物表达与生存结果之间存在统计学显著关联。根据单因素分析结果,较高的uPAR表达水平有OS降低的趋势(P=0.07;风险比=2.01;95%置信区间=0.92-4.37)。综上所述,这些结果表明uPAR、TF和EGFR可能是OPSCC分子成像和治疗的合适靶点。特别是,uPAR可能是一个有吸引力的靶点,因为它们在肿瘤中的阳性表达率高且具有高度肿瘤特异性的表达模式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5c8/9263836/9e7892d64ee8/or-48-02-08359-g00.jpg

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