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LAMB3 与头颈部鳞状细胞癌的疾病进展和顺铂细胞毒性敏感性相关。

LAMB3 is associated with disease progression and cisplatin cytotoxic sensitivity in head and neck squamous cell carcinoma.

机构信息

Department of Medical Science, College of Medicine, Chungnam National University, Daejeon, Republic of Korea; Department of Otorhinolaryngology-Head and Neck Surgery, Yanbian University Hospital, Yanji, China.

Department of Otolaryngology-Head and Neck Surgery, Research Institute for Medical Science, Chungnam National University College of Medicine, Daejeon, Republic of Korea.

出版信息

Eur J Surg Oncol. 2019 Mar;45(3):359-365. doi: 10.1016/j.ejso.2018.10.543. Epub 2018 Nov 2.

Abstract

OBJECTIVES

Laminin subunit beta-3 (LAMB3) is a major component of the basement membrane zone. In our study, we investigated the role of LAMB3 in head and neck squamous cell carcinoma (HNSCC) progression and its clinical implication as a prognostic biomarker.

MATERIALS AND METHODS

A retrospective analysis of 100 patients with HNSCC who had undergone curative surgery from 1999 to 2011 was performed. We evaluated LAMB3 expression by immunohistochemistry and its associations with clinicopathological characteristics and survival. For functional in vitro analyses, cell proliferation, migration, and invasion and western blot assays were performed following LAMB3 suppression. In addition, the role of LAMB3 in cisplatin-induced cytotoxicity was clarified by measuring cell proliferation.

RESULTS

LAMB3 expression was up-regulated in HNSCC cell lines and patient tissues. High LAMB3 expression was significantly associated with positive lymph node metastasis (odds ratio: 6.316; P < 0.001) and poor prognosis in patients with HNSCC. LAMB3 suppression reduced cell migration/invasion via down-regulation of epithelial-to-mesenchymal transition-associated proteins (Vimentin and Slug). Moreover, LAMB3 suppression increased cisplatin cytotoxicity in HNSCC cells.

CONCLUSION

Our findings indicate that LAMB3 may be used as a prognostic biomarker in HNSCC and support that LAMB3 silencing could induce the sensitivity of anti-cancer drugs such as cisplatin.

摘要

目的

层粘连蛋白亚单位β-3(LAMB3)是基底膜区的主要成分。在本研究中,我们研究了 LAMB3 在头颈部鳞状细胞癌(HNSCC)进展中的作用及其作为预后生物标志物的临床意义。

材料与方法

对 1999 年至 2011 年期间接受根治性手术的 100 例 HNSCC 患者进行回顾性分析。我们通过免疫组织化学评估 LAMB3 的表达,并分析其与临床病理特征和生存的关系。为了进行功能的体外分析,在抑制 LAMB3 后进行细胞增殖、迁移和侵袭以及 Western blot 检测。此外,通过测量细胞增殖来阐明 LAMB3 在顺铂诱导的细胞毒性中的作用。

结果

LAMB3 在 HNSCC 细胞系和患者组织中呈上调表达。高 LAMB3 表达与阳性淋巴结转移显著相关(优势比:6.316;P<0.001),并与 HNSCC 患者的预后不良相关。LAMB3 抑制通过下调上皮间质转化相关蛋白(波形蛋白和 Slug)降低细胞迁移/侵袭。此外,LAMB3 抑制增加了 HNSCC 细胞中顺铂的细胞毒性。

结论

我们的研究结果表明,LAMB3 可作为 HNSCC 的预后生物标志物,并支持 LAMB3 沉默可诱导顺铂等抗癌药物的敏感性。

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