晚期非小细胞肺癌预后相关基因对顺铂及紫杉醇敏感性分析

Sensitivity Analysis of Genes Related to Prognosis of Advanced Non-small Cell Lung Cancer to Cisplatin and Paclitaxel

关键词:  非小细胞肺癌  预后  顺铂  紫杉醇  敏感性

Key words:  non-small cell lung cancer  prognosis  cisplatin  paclitaxel  sensitivity

摘要:

目的 利用生物信息学方法探讨晚期非小细胞肺癌预后相关基因的表达与化疗药物紫杉醇及顺铂敏感性变化的相关性。方法 通过肿瘤基因组图谱数据库下载非小细胞肺癌病例的基因表达谱与相应的临床信息。筛选正常组织样本和癌组织样本之间的差异表达基因。加权基因共表达网络分析确定与临床分期相关的枢纽基因，单因素Cox分析确定预后相关的差异表达基因。通过抗癌药物敏感性基因组学数据库下载整合非小细胞肺癌细胞系的表达量及细胞系与药物反应的基因数据，分析非小细胞肺癌预后和临床分期都相关的差异表达基因对紫杉醇及顺铂药物敏感度的相关性。结果 鉴定出4个基因与紫杉醇敏感性反应具有相关性；8个基因与顺铂敏感性反应具有相关性。SPATS2和CA3表达量的变化与紫杉醇及顺铂敏感性反应均具有相关性，CA3表达量的增加对紫杉醇及顺铂耐药性增强，SPATS2表达量的增加对紫杉醇及顺铂敏感性增强。结论 晚期非小细胞肺癌患者CA3和SPATS2基因的表达量的增加对紫杉醇及顺铂的药物作用活性分别是耐药性增强和敏感性增强。

Abstract:

OBJECTIVE To explore the correlation between the expression of prognostic genes in advanced non-small cell lung cancer and the sensitivity changes of the paclitaxel and cisplatin of chemotherapy drugs by using bioinformatics methods. METHODS Download the gene expression profile and corresponding clinical information of non-small cell carcinoma cases through the the cancer genome atlas. Screen hub gene between normal tissue samples and cancer tissue samples. Weighted gene co-expression network analysis determined pivot genes related to clinical stage, and univariate Cox analysis determined differential gene related to prognosis. Download genomics of drug sensitivity in cancer to integrate the expression data of non-small cell lung cancer cell line and the genetic data of cell line and drug response, to analyze the correlation between the differential gene expression related to the prognosis and clinical stage of non-small cell lung cancer to the sensitivity of paclitaxel and cisplatin drugs. RESULTS Four genes were identified to be related to paclitaxel sensitivity reaction; eight genes were related to cisplatin sensitivity reaction. Changes in the expression levels of SPATS2 and CA3 were correlated with the sensitivity responses of paclitaxel and cisplatin. Increased expression levels of CA3 increased resistance to paclitaxel and cisplatin. Increased expression levels of SPATS2 increased sensitivity to paclitaxel and cisplatin. CONCLUSION The increased expression of CA3 and SPATS2 genes in patients with advanced non-small cell lung cancer have enhanced drug resistance and increased sensitivity to paclitaxel and cisplatin, respectively.