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喉鳞状细胞癌非侵入性生物标志物的早期检测与纵向随访:BEAL研究的初步结果

Early Detection and Longitudinal Follow-Up of Non-Invasive Biomarkers for Laryngeal Squamous Cell Carcinoma: First Results of the BEAL-Study.

作者信息

Winkelmann Ann-Christin, Wendler Olaf, Schuster Johannes, Agaimy Abbas, Haderlein Marlen, Frey Benjamin, Mueller Sarina Katrin

机构信息

Department of Otolaryngology, Head and Neck Surgery, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

Department of Pathology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

出版信息

Cancer Med. 2025 May;14(10):e70961. doi: 10.1002/cam4.70961.

DOI:10.1002/cam4.70961
PMID:40365873
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12076192/
Abstract

INTRODUCTION

Despite therapeutic and prognostic improvements in the early treatment of laryngeal squamous cell carcinoma (LSCC), screening for early detection of laryngeal cancer has not yet been established.

METHODS

A study has been designed to address this issue based on an analysis of exosomal serum biomarkers for LSCC. A three-step approach was used. Firstly, the serum biomarkers Nov and uPAR were validated in control and LSCC patients using a standardized enzyme-linked immunosorbent assay (ELISA). Subsequently, an immunohistochemical comparison was conducted. Secondly, the ELISA results were compared with patients with benign laryngeal lesions. Thirdly, a prospective study compared preoperative and postoperative values. The study is ongoing.

RESULTS

In the initial comparison of the control group with tumor patients at the time of diagnosis, Nov and uPAR demonstrated significant overexpression in LSCC patients' serum. In Step 2, the comparison with the cohort of benign laryngeal lesions revealed that both biomarkers were also significantly overexpressed here. Nevertheless, uPAR effectively differentiated between control, benign, and malignant lesions. In the third step, the observations in the postoperative course demonstrated that the serum concentrations of Nov and uPAR were elevated in both groups with laryngeal diseases but declined faster in patients with benign lesions.

CONCLUSION

uPAR and Nov may serve as valuable biomarkers for early detection and disease monitoring. Further investigation is required to ascertain their suitability, including an extended follow-up period and a larger study population. For this reason, this study is still ongoing, and only initial results are presented here. This study's objective is to examine the potential of Nov and uPAR as serum biomarkers for early detection and follow-up of LSCC. We compare them in a control group, tumor group, and first-time benign laryngeal diseases and monitor a long-term follow-up. This aims to deepen understanding of suitability for early detection and follow-up and provide future research insights.

TRIAL REGISTRATION

DRKS00033427.

摘要

引言

尽管喉鳞状细胞癌(LSCC)的早期治疗在治疗效果和预后方面有所改善,但尚未建立用于早期检测喉癌的筛查方法。

方法

基于对LSCC外泌体血清生物标志物的分析,设计了一项研究来解决这一问题。采用了三步法。首先,使用标准化酶联免疫吸附测定(ELISA)在对照组和LSCC患者中验证血清生物标志物Nov和uPAR。随后,进行免疫组化比较。其次,将ELISA结果与喉良性病变患者进行比较。第三,一项前瞻性研究比较了术前和术后的值。该研究正在进行中。

结果

在诊断时将对照组与肿瘤患者进行的初步比较中,Nov和uPAR在LSCC患者血清中表现出显著过表达。在第二步中,与喉良性病变队列的比较显示,这两种生物标志物在这里也显著过表达。然而,uPAR有效地区分了对照、良性和恶性病变。在第三步中,术后过程中的观察表明,两种喉疾病组中Nov和uPAR的血清浓度均升高,但良性病变患者下降得更快。

结论

uPAR和Nov可能作为早期检测和疾病监测的有价值生物标志物。需要进一步研究以确定它们的适用性,包括延长随访期和扩大研究人群。因此,本研究仍在进行中,此处仅展示初步结果。本研究的目的是检验Nov和uPAR作为LSCC早期检测和随访血清生物标志物的潜力。我们在对照组、肿瘤组和首次发生的喉良性疾病组中对它们进行比较,并进行长期随访监测。这旨在加深对早期检测和随访适用性的理解,并提供未来的研究见解。

试验注册

DRKS00033427

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be75/12076192/28d04e663332/CAM4-14-e70961-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be75/12076192/aadc7e032757/CAM4-14-e70961-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be75/12076192/ab42239a0b56/CAM4-14-e70961-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be75/12076192/b0413223d1db/CAM4-14-e70961-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be75/12076192/67fb0a978765/CAM4-14-e70961-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be75/12076192/28d04e663332/CAM4-14-e70961-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be75/12076192/aadc7e032757/CAM4-14-e70961-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be75/12076192/ab42239a0b56/CAM4-14-e70961-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be75/12076192/b0413223d1db/CAM4-14-e70961-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be75/12076192/67fb0a978765/CAM4-14-e70961-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be75/12076192/28d04e663332/CAM4-14-e70961-g005.jpg

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Plasma IL-6, TREM1, uPAR, and IL6/IL8 biomarkers increment further witnessing the chronic inflammation in type 2 diabetes.血浆白细胞介素-6、触发受体表达分子-1、尿激酶型纤溶酶原激活物受体和白细胞介素-6/白细胞介素-8生物标志物进一步升高,这进一步证明了2型糖尿病中的慢性炎症。
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CCN3/NOV promotes metastasis and tumor progression via GPNMB-induced EGFR activation in triple-negative breast cancer.
CCN3/NOV 通过 GPNMB 诱导的 EGFR 激活促进三阴性乳腺癌的转移和肿瘤进展。
Cell Death Dis. 2023 Feb 3;14(2):81. doi: 10.1038/s41419-023-05608-3.
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Urokinase-type plasminogen activator receptor (uPAR) assessed by liquid biopsies and PET/CT for prognostication in head and neck cancer patients.液体活检和 PET/CT 评估尿激酶型纤溶酶原激活物受体(uPAR)在头颈部癌症患者中的预后价值。
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Liquid biopsy: current technology and clinical applications.液体活检:当前技术与临床应用。
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Targeting uPA-uPAR interaction to improve intestinal epithelial barrier integrity in inflammatory bowel disease.靶向 uPA-uPAR 相互作用改善炎症性肠病的肠道上皮屏障完整性。
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Predicting Response to Radiotherapy in Cancer-Induced Bone Pain: Cytokines as a Potential Biomarker?预测癌症骨痛放疗反应:细胞因子是否为潜在的生物标志物?
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