Isolation, Detection, and Quantification of Cancer Biomarkers in HPV-Associated Malignancies.

Isolation, Detection, and Quantification of Cancer Biomarkers in HPV-Associated Malignancies.
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DOI:
10.1038/s41598-017-02672-6
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发表时间:
2017-06-12
期刊:
影响因子:
4.6
通讯作者:
Demirci U
Demirci U
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Inan H;Wang S;Inci F;Baday M;Zangar R;Kesiraju S;Anderson KS;Cunningham BT;Demirci U

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人乳头瘤病毒(HPV)感染是导致阴茎癌、外阴癌、口咽癌和宫颈癌等多种癌症的主要病因。在癌症的发展中,持续的HPV感染诱导E6和E7癌蛋白,其促进细胞增殖和致癌,导致宿主抗体(例如,抗HPV 16 E7抗体)。目前,这些癌症是使用基于侵入性活检的测试进行临床诊断的,这些测试仅由经验丰富的临床工作人员使用耗时且昂贵的工具和技术在集中实验室中进行。因此,这些障碍限制了它们在初级保健诊所和资源有限的偏远地区的使用。在这里,我们提出了一种快速,廉价,可靠,易于使用,定制的免疫分析平台,在微流控过滤器装置之后检测和定量全血中的抗HPV 16 E7抗体,作为HPV相关恶性肿瘤诊断的非侵入性辅助技术,特别是在初级医疗保健和远程设置中。该平台可以检测和定量抗HPV 16 E7抗体,最低可达2.87 ng/mL。我们在临床患者样品中进一步验证了我们的免疫测定,与对照样品相比,它提供了显著高的响应。因此,它可以作为一种预测试工具来识别高危人群,以便在资源有限的环境中广泛监测HPV相关癌症。
Human Papillomavirus (HPV) infection has been recognized as the main etiologic factor in the development of various cancers including penile, vulva, oropharyngeal and cervical cancers. In the development of cancer, persistent HPV infections induce E6 and E7 oncoproteins, which promote cell proliferation and carcinogenesis resulting elevated levels of host antibodies (e.g., anti-HPV16 E7 antibody). Currently, these cancers are clinically diagnosed using invasive biopsy-based tests, which are performed only in centralized labs by experienced clinical staff using time-consuming and expensive tools and technologies. Therefore, these obstacles constrain their utilization at primary care clinics and in remote settings, where resources are limited. Here, we present a rapid, inexpensive, reliable, easy-to-use, customized immunoassay platform following a microfluidic filter device to detect and quantify anti-HPV16 E7 antibodies from whole blood as a non-invasive assisting technology for diagnosis of HPV-associated malignancies, especially, at primary healthcare and remote settings. The platform can detect and quantify anti-HPV16 E7 antibody down to 2.87 ng/mL. We further validated our immunoassay in clinical patient samples and it provided significantly high responses as compared to control samples. Thus, it can be potentially implemented as a pretesting tool to identify high-risk groups for broad monitoring of HPV-associated cancers in resource-constrained settings.