DSG3 as a biomarker for the ultrasensitive detection of occult lymph node metastasis in oral cancer using nanostructured immunoarrays.
DSG3 as a biomarker for the ultrasensitive detection of occult lymph node metastasis in oral cancer using nanostructured immunoarrays.
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DOI：
10.1016/j.oraloncology.2012.08.001
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发表时间：
2013-02
期刊：
影响因子：
4.8
通讯作者：
Gutkind, J. Silvio
中科院分区：
文献类型：
--
作者：
Patel, Vyomesh;Martin, Daniel;Malhotra, Ruchika;Marsh, Christina A.;Doci, Colleen L.;Veenstra, Timothy D.;Nathan, Cherie-Ann O.;Sinha, Uttam K.;Singh, Bhuvanesh;Molinolo, Alfredo A.;Rusling, James F.;Gutkind, J. Silvio
关键词：
头颈部鳞状细胞癌(HNSCC)患者颈淋巴转移的诊断是临床分期和治疗选择的基本要求。然而，通过体检和不同的成像方式以及常规淋巴结冷冻切除的组织学检查进行临床评估，可能会漏掉微转移，而假阳性可能会导致不必要的选择性淋巴结颈部切除。在这里，我们探讨了开发一种灵敏的桥粒芯糖蛋白3(DSG3)检测系统作为预测HNSCC淋巴结转移的生物标志物的可行性。检测DSG3在多种普通癌和HNSCC组织芯片(TMA)、阴性和阳性HNSCC转移淋巴结以及多种HNSCC和对照细胞系中的表达。建立了一种超灵敏检测淋巴结组织裂解液中DSG3的纳米免疫阵列系统。我们发现DSG3在所有HNSCC病变及其转移性颈淋巴结中都有高表达，但在非侵袭性淋巴结中不表达。我们发现，使用简单的微流控免疫阵列平台，即使在包含极少数HNSCC侵袭细胞的人体组织切片中，DSG3也可以以高灵敏度快速检测，从而区分阳性和阴性淋巴结节。我们提供了支持DSG3超灵敏的纳米结构检测系统可用于检测淋巴结微转移的HNSCC病变的原理证据，这可以提高HNSCC患者的诊断和指导选择合适的治疗干预方案。
The diagnosis of cervical lymph node metastasis in head and neck squamous cell carcinoma (HNSCC) patients constitutes an essential requirement for clinical staging and treatment selection. However, clinical assessment by physical examination and different imaging modalities, as well as by histological examination of routine lymph node cryosections can miss micrometastases, while false positives may lead to unnecessary elective lymph node neck resections. Here, we explored the feasibility of developing a sensitive assay system for desmoglein 3 (DSG3) as a predictive biomarker for lymph node metastasis in HNSCC. DSG3 expression was determined in multiple general cancer- and HNSCC-tissue microarrays (TMA), in negative and positive HNSCC metastatic cervical lymph nodes, and in a variety of HNSCC and control cell lines. A nanostructured immunoarray system was developed for the ultrasensitive detection of DSG3 in lymph node tissue lysates. We demonstrate that DSG3 is highly expressed in all HNSCC lesions and their metastatic cervical lymph nodes, but absent in non-invaded lymph nodes. We show that DSG3 can be rapidly detected with high sensitivity using a simple microfluidic immunoarray platform, even in human tissue sections including very few HNSCC invading cells, hence distinguishing between positive and negative lymph nodes. We provide a proof of principle supporting that ultrasensitive nanostructured assay systems for DSG3 can be exploited to detect micrometastatic HNSCC lesions in lymph nodes, which can improve the diagnosis and guide in the selection of appropriate therapeutic intervention modalities for HNSCC patients.
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影响因子：
12.6
作者：
Chikkaveeraiah, Bhaskara V.;Mani, Vigneshwaran;Patel, Vyomesh;Gutkind, J. Silvio;Rusling, James F.
通讯作者：
Rusling, James F.
影响因子：
3.4
作者：
Clark, Jonathan R.;Naranjo, Natalie;Gullane, Patrick J.
通讯作者：
Gullane, Patrick J.
影响因子：
2.5
作者：
Leong, Stanley P. L.;Zuber, Markus;Saha, Sukamal
通讯作者：
Saha, Sukamal
影响因子：
2.6
作者：
Phan, Giao Q.;Messina, Jane L.;Zager, Jonathan S.
通讯作者：
Zager, Jonathan S.
影响因子：
6.5
作者：
Amagai, Masayuki;Stanley, John R.
通讯作者：
Stanley, John R.