喉鳞状细胞癌肿瘤发生及区域淋巴结转移的基因芯片基因表达分析
Microarray gene expression analysis of tumorigenesis and regional lymph node metastasis in laryngeal squamous cell carcinoma.
作者信息
Lian Meng, Fang Jugao, Han Demin, Ma Hongzhi, Feng Ling, Wang Ru, Yang Fan
机构信息
Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China ; Key Laboratory of Otorhinolaryngology Head and Neck Surgery, Ministry of Education, Beijing Institute of Otorhinolaryngology, Beijing, China.
出版信息
PLoS One. 2013 Dec 26;8(12):e84854. doi: 10.1371/journal.pone.0084854. eCollection 2013.
BACKGROUND
Laryngeal squamous cell carcinoma (LSCC) is the most common type in head and neck squamous cell carcinoma (HNSCC), and the development and progression of LSCC are multistep processes accompanied by changes of molecular biology.
OBJECTIVE
The purpose of this study was to investigate the molecular basis of tumorigenesis and regional lymph node metastasis in LSCC, and provide a set of genes that may be useful for the development of novel diagnostic markers and/or more effective therapeutic strategies.
METHODS
A total number of 10 patients who underwent surgery for primary laryngeal squamous cell carcinoma were recruited for microarray analysis. LSCC tissues compared with corresponding adjacent non-neoplastic tissues were analysed by Illumina mRNA microarrays, and LSCC tissues with regional lymph node metastasis and LSCC tissues without regional lymph node metastasis were analyzed in the same manner. The most frequently differently expressed genes screened by microarrays were also validated by qRT-PCR in another 42 patients diagnosed for LSCC.
RESULTS
Analysed by Illumina mRNA microarrays, there were 361 genes significantly related to tumorigenesis while 246 genes significantly related to regional lymph node metastasis in LSCC. We found that the six genes (CDK1, CDK2, CDK4, MCM2, MCM3, MCM4) were most frequently differently expressed functional genes related to tumorigenesis while eIF3a and RPN2 were most frequently differently expressed functional genes related to regional lymph node metastasis in LSCC. The expressions of these genes were also validated by qRT-PCR.
CONCLUSIONS
The research revealed a gene expression signature of tumorigenesis and regional lymph node metastasis in laryngeal squamous cell carcinoma. Of the total, the deregulation of several genes (CDK1, CDK2, CDK4, MCM2, MCM3, MCM4, EIF3a and RPN2) were potentially associated with disease development and progression. The result will contribute to the understanding of the molecular basis of LSCC and help to improve diagnosis and treatment.
背景
喉鳞状细胞癌（LSCC）是头颈部鳞状细胞癌（HNSCC）中最常见的类型，LSCC的发生和发展是一个多步骤过程，伴有分子生物学变化。
目的
本研究旨在探讨LSCC肿瘤发生及区域淋巴结转移的分子基础，并提供一组可能有助于开发新型诊断标志物和/或更有效治疗策略的基因。
方法
招募10例接受原发性喉鳞状细胞癌手术的患者进行微阵列分析。通过Illumina mRNA微阵列分析LSCC组织与其相应的相邻非肿瘤组织，并以相同方式分析有区域淋巴结转移的LSCC组织和无区域淋巴结转移的LSCC组织。通过微阵列筛选出的最常差异表达的基因也在另外42例诊断为LSCC的患者中通过qRT-PCR进行验证。
结果
通过Illumina mRNA微阵列分析，在LSCC中有361个基因与肿瘤发生显著相关，246个基因与区域淋巴结转移显著相关。我们发现六个基因（CDK1、CDK2、CDK4、MCM2、MCM3、MCM4）是LSCC中与肿瘤发生最常差异表达的功能基因，而eIF3a和RPN2是LSCC中与区域淋巴结转移最常差异表达的功能基因。这些基因的表达也通过qRT-PCR得到验证。
结论
该研究揭示了喉鳞状细胞癌肿瘤发生及区域淋巴结转移的基因表达特征。其中，几个基因（CDK1、CDK2、CDK4、MCM2、MCM3、MCM4、EIF3a和RPN2）的失调可能与疾病的发生和发展有关。该结果将有助于理解LSCC的分子基础，并有助于改善诊断和治疗。
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