OBJECTIVE Several genes have been validated as molecular targets for gene therapy in lung cancer. We screened target genes that affect survival of patients with lung cancer. METHODS Data on gene expression in normal lung tissues/lung adenocarcinoma (LUAD) samples were acquired from Genotype-Tissue Expression (GTEx)/The Cancer Genome Atlas (TCGA) databases and merged to expand the sample size, followed by differential analysis of the merged expression data and acquisition of differentially expressed genes. Survival and simple Cox analyses were used to screen for genes affecting LUAD survival. Protein-protein interaction/multivariable Cox analyses were utilized, and a risk model was established. Candidate genes expression levels in cancer/paracancerous tissues of lung cancer patients, and BEAS-2B/A549/HCC95 cells were measured by RT-qPCR/Western blot. Survival analysis of candidate genes was conducted in LUAD samples collected from TCGA. RESULTS Among 947 genes differentially expressed in LUAD, 151 were correlated with patient survival, and 116 might act as risk factors for LUAD. The 7 identified candidate genes (TOP2A, TK1, KIF4A, ANLN, KIF2C, ASF1B, CCNB1) were high-risk genes playing possible roles in LUAD. These genes were differentially expressed in lung cancer and were associated with TNM stages (III - IV)/differentiation grade/lymph node metastasis/distant metastasis, which affected lung cancer patient survival. CONCLUSION P2A, TK1, KIF4A, ANLN, KIF2C, ASF1B and CCNB1 were highly-expressed in LUAD/lung squamous cell carcinoma (LUSC) and correlated with LUAD patient survival. This study contributes to better understanding of the prognostic regulation mechanism in LUAD and the screening of target genes for clinical treatment.

中文翻译：

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肺癌预后相关潜在靶基因的生物信息学分析及筛选。

目的 多个基因已被验证为肺癌基因治疗的分子靶点。我们筛选了影响肺癌患者生存的靶基因。方法从基因型组织表达（GTEx）/癌症基因组图谱（TCGA）数据库中获取正常肺组织/肺腺癌（LUAD）样本中基因表达的数据，并合并以扩大样本量，然后对合并后的样本进行差异分析。表达数据和差异表达基因的获取。使用生存分析和简单的 Cox 分析来筛选影响 LUAD 生存的基因。利用蛋白质-蛋白质相互作用/多变量Cox分析，并建立了风险模型。通过RT-qPCR/Western blot检测肺癌患者癌/癌旁组织和BEAS-2B/A549/HCC95细胞中候选基因的表达水平。对从 TCGA 收集的 LUAD 样本进行候选基因的生存分析。结果 LUAD 差异表达的 947 个基因中，151 个与患者生存相关，116 个可能作为 LUAD 的危险因素。确定的 7 个候选基因（TOP2A、TK1、KIF4A、ANLN、KIF2C、ASF1B、CCNB1）是在 LUAD 中可能发挥作用的高风险基因。这些基因在肺癌中差异表达，并与TNM分期（III-IV）/分化级别/淋巴结转移/远处转移相关，影响肺癌患者的生存。结论 P2A、TK1、KIF4A、ANLN、KIF2C、ASF1B 和 CCNB1 在 LUAD/肺鳞状细胞癌 (LUSC) 中高表达，并与 LUAD 患者生存相关。本研究有助于更好地理解LUAD的预后调控机制以及临床治疗靶基因的筛选。