Study on the Difference of Gene Expression between Central and Peripheral Lung Squamous Cell Carcinoma Based on TCGA Database

: 【中文题目：基于TCGA数据库的中央型与周围型肺鳞癌基因表达差异性研究】 【中文摘要：背景与目的 肺癌是一种具有高发病率与高死亡率的恶性肿瘤疾病，最常见的类型为非小细胞肺癌（non-small cell lung cancer, NSCLC），其中肺鳞癌作为NSCLC中的一个亚型，具有特殊的病理学类型及其特定的治疗方法，根据临床表型不同又可分为周围型和中央型。本研究基于中央型和周围型肺鳞癌的临床差异进一步探索其基因水平的差异和其潜在的价值。方法 从癌症基因组图谱（The Cancer Genome Atlas, TCGA）数据库收集肺鳞癌数据集，下载临床信息资料及基因表达谱资料。整理资料，分析临床数据及相对应的基因信息。结果 在临床特征分析中发现，中央型肺鳞癌较周围型肺鳞癌更容易发生淋巴结转移（46.2%, 67/145 vs 28.9%, 26/90; P=0.019），而在性别、年龄、肿瘤大小、有无远处转移、TNM分期、表皮生长因子受体（epidermal growth factor receptor, EGFR）突变等方面未见明显差异。在基因表达水平分析中发现，中央型与周围型肺鳞癌具有1,031个差异表达基因，其中，周围型与中央型相比，629个基因表达水平上调，402个基因表达水平下调。进一步富集分析显示差异表达基因主要体现在6个信号通路中，其中，刺激神经组织的配体-受体相互作用（neuroactive ligand-receptor interaction）通路是差异表达基因主要富集通路，其他差异表达基因主要与脂类代谢和糖代谢有关。相互作用网络分析显示，在表达上调差异基因中，肝细胞核因子1同源体A（hepatocyte nuclear factor 1 homeobox A, HNF1A）和细胞色素P450家族里的A亚家族发现的第四种酶（cytochrome p450 family, Cytochrome P450 3A4, CYP3A4）影响较为广泛，在表达下调差异基因中，人血清白蛋白（Albumin, ALB）与 载脂蛋白A1（Apolipoprotein, APOA1）位于该作用网络的关键位置。结论 中央型和周围型肺鳞癌患者不仅在淋巴结转移发生率上存在临床特征的差异，而且在基因表达水平亦有明显的不同。其中，HNF1A、CYP3A4、ALB、APOA1位于差异基因相互作用网络的关键位置，有可能参与调控二者的差异表型（phenotypic difference）。】 【中文关键词：肺肿瘤；中央型；周围型；预后】. METHODS: The lung squamous cell carcinoma dataset was collected from The Cancer Genome Atlas (TCGA) database, clinical information and the corresponding gene expression profiles were downloaded. Then we further sort and analyze all these data. RESULTS: In clinical characteristics analysis, result showed that central lung squamous cell carcinoma was more likely to metastasis with lymph node than peripheral lung squamous cell carcinoma (46.2%, 67/145 vs 28.9%, 26/90; P=0.019), while there were no significant differences in gender, age, tumor size, distant metastasis, tumor node metastasis (TNM) stage, and EGFR mutation. Gene expression analysis showed 1,031 differentially expressed genes between central and peripheral lung squamous cell carcinoma, of which 629 genes were up-regulated and 402 genes were down-regulated (peripheral vs central). Further enrichment analysis showed differentially expressed genes were mainly riched in 6 signaling pathways. Among them, the neuroactive ligand-receptor interaction pathway was the main enrichment pathway of differentially expressed genes, and other differential expressed genes were mainly involved in lipid metabolism and glucose metabolism. The analysis of interaction network showed that hepatocyte nuclear factor 1 homeobox A (HNF1A) and cytochrome p450 family, Cytochrome P450 3A4 (CYP3A4) own widely effect in up-regulated genes, while ALB and APOA1 at the key positions of the network in down-regulated genes were CONCLUSIONS: Central and peripheral lung squamous cell carcinoma showed clinical phenotype difference not only reflected in the incidence of lymph node metastasis, but also in gene expression profiles. Among them, HNF1A, CYP3A4, ALB, APOA1 at the key position of the differential gene interaction network and maybe as regulatory factors in the phenotypic difference.