Wu Wei, Wang Xianwei, Shan Changting, Li Yong, Li Fengzhu
Department of Respiratory Medicine, Affiliated Hospital of Jining Medical University, Jining, Shandong 272029, People's Republic of China,
Department of Emergency, Affiliated Hospital of Jining Medical University, Jining, Shandong 272029, People's Republic of China.
Onco Targets Ther. 2018 Aug 20;11:5025-5034. doi: 10.2147/OTT.S169002. eCollection 2018.
Minichromosome maintenance protein 2 (MCM2), which is a member of MCM family, has been found to be a relevant marker for progression and prognosis in a variety of human cancers. Due to lack of effective therapeutic target in lung squamous cell carcinoma (LUSC) patients, the aim of our study was to screen and identify biomarkers which are associated to clinicopathological characteristics including prognosis in LUSC patients.
The expression status of MCM2 in lung cancer was analyzed using the publicly available Gene Expression Omnibus databases (GSE3268 and GSE10245). The mRNA and protein expression of MCM2 in lung cancer tissues and cell lines was detected by quantitative real-time PCR and Western blot, and the association between MCM2 expression and clinicopathological factors was analyzed by immunohistochemistry. The loss-of-function study of MCM2 was conducted in LUSC cell lines.
In our study, we found MCM2 expression was increased in LUSC tissues compared with paired adjacent normal lung tissues or lung adenocarcinoma tissues through analyzing microarray data sets (GSE3268 and GSE10245), which confirmed that MCM2 mRNA and protein were overexpressed in LUSC tissues and cell lines. Meanwhile, we analyzed the association between MCM2 protein expression and clinicopathological characteristics of LUSC patients, and found high expression of MCM2 protein was obviously associated with malign differentiated degree, advanced clinical stage, large tumor size, more lymph node metastasis and present distant metastasis. The survival analysis showed MCM2 overexpression was an independent unfavorable prognostic factor for LUSC patients.
MCM2 is involved in the development and progression of LUSC as an oncogene, and thereby may act as a potential therapeutic target for LUSC patients.
微小染色体维持蛋白2（MCM2）是MCM家族的成员，已被发现是多种人类癌症进展和预后的相关标志物。由于肺鳞状细胞癌（LUSC）患者缺乏有效的治疗靶点，我们研究的目的是筛选和鉴定与LUSC患者的临床病理特征（包括预后）相关的生物标志物。
使用公开可用的基因表达综合数据库（GSE3268和GSE10245）分析肺癌中MCM2的表达状态。通过定量实时PCR和蛋白质印迹检测肺癌组织和细胞系中MCM2的mRNA和蛋白质表达，并通过免疫组织化学分析MCM2表达与临床病理因素之间的关联。在LUSC细胞系中进行MCM2的功能丧失研究。
在我们的研究中，通过分析微阵列数据集（GSE3268和GSE10245），我们发现与配对的相邻正常肺组织或肺腺癌组织相比，LUSC组织中MCM2表达增加，这证实了MCM2 mRNA和蛋白质在LUSC组织和细胞系中过表达。同时，我们分析了MCM2蛋白表达与LUSC患者临床病理特征之间的关联，发现MCM2蛋白的高表达与恶性分化程度、晚期临床分期、肿瘤体积大、更多淋巴结转移和存在远处转移明显相关。生存分析表明，MCM2过表达是LUSC患者独立的不良预后因素。
MCM2作为一种癌基因参与LUSC的发生和发展，因此可能成为LUSC患者潜在的治疗靶点。
